and pharmaceutically acceptable salts and esters thereof, wherein ., I Rl is hydrogen, alkyl, alkoxyaTkyl, alkeriyl ; alkiriyl, hydroxyalkyl,'aralkyl, heterocyclylalkyl, cycloalkylalkyl, NH2-S02-, monoalkylamino-S02-, dialkylamino-SO2-, alkyl-SO2-, aryl, NH2-alkyl, monoalkylaminoalkyl, dialkylaminoalkyl, alkoxycarbonylalkyl, carboxyalkyl, aryl-SO2-O-alkyl, cycloalkyl or cycloalkylalkyl ; R2 is hydrogen, halogen, alkyl, alkenyl, alkinyl, aralkyl, heteroarylalkyl, hydroxyalkyl, alkoxy,alkoxyalkoxy, hydroxyalkoxyalkyl,. aryloxy,, arylamino,

heteroarylamin, 6NH2-, monoalkylamino, dialkylamino, heterocyclyl, arylalkylamir y alko or heteroarylalkoxy ; R3 is hydrogen, al'kyl, HHz-, monoalkylamino,. dialkylamino or alkoxy ; - ''t R is hydrogen, alky : cydoalkyl, alkoxy,-hydroxy, NH. 2-, monoalkylamino,' diaIkylaminOy-atylaminQ, eyanQ,-hydroxyalkyi', alkoxyalkyi, cydoalkoxy, alkoxyalkox,''"lk'yla<o he c'ycl 4r, heterocyclyiWxy, hydroxyalkoxy, aikoxyarbönyI, carboxy, heterocyclyiali4-ç702-or aryl-SO2-;..- ; ; RS is hydrogen, alykyl, cyeloalkyl, alkoxy, hydroxy, NH2-, monoalkylamino, a,.,- dialkylamyo, acetylamino, canp, hydro, xya, lkyl alkoFxyalkyla, cyclo. alkoxy, alkoxyalkoxy, cydpalkylapxy, heterpcydyl, h ; terocyd) d . i.,'.- heterocydyldxyalkoxy, hydroxyalkoxy, alkoxycarbonyl, carboxy, yjalkoxy, hete heterocycly ! 6'yi"" h*d xy, alko) cycarbonyl, carboxy, ..., ;..., °..,,,,.. _., _,... A is a 5-to 10-membeemonoMbr bicydic'satu the nitrogenat6m. which is attaehedtto'th'qu'in and optionally one or two further heteroatoin, which are indepeiideritly selectedfrom oxygen, sulfur and riittogen : ; i u..,... The compounds of formula I and their pharmaceutically usable salts and are novel and have valuable pharmacological properties. They are neuropeptide ligands, for example neuropeptide receptór árSm js ; Es and irittiårticX ; tlieyk, å ; re selective neur, opep ; tides Y Y5 neuropeptide receptorantgoW sts.'aiid iii, particul ; ax, ; they are, seletive, neuropeptides Y Y5 Neuropetideantagonists --.,.... .,. _ . ;. f.. Neuropetide Y as a'6 arymo ; acml eptide. that is wxdelyclistributed. in. the central and peripheral nervous systems.'This peptide mediates a number 6f physiological effects through its various je-'a-'n-h6Wift"iha : t ne iropiptide is a powerful stimulus dfdS'Rtake. andifhas'leen'den activation of neuropeptide Y Y5 receptorsesults in hyperphagia'ahd decreas'ed thermogenesis. Therefore compound subtype represent an approach to the treatment of eating disorders such as obesity and hyperphagia. The current approach-is aiming at'medical intervention t6 induce weight loss or' prevention of weight gaiAl=This4s achieved by interfermg with. appetite control, which is mediated by the Hyppjitalamus ;, animpprtant, brain region prYen. to control food intake. Herein, neuropeptide Y'NPY) 3iasbeeh proven to be one ofthe strohgest central

mediators of food intake in several animal species. Increased NPY levels result in profound ..,."....."...... food intake. Various receptors of neuropeptide Y (NPY) have been described to play a role in appetite control and weight gain. Interference-with these receptors is likely to reducé appetite and consequently weight gain. Reduction and long-term maintenance of body weight can also have benencial Consequences on con associated risk factors such as arthritis, cardiovascular'ci. iseases, dialetes andvrenaI failure. Accordingly, the wowof fok-ula T can be used in. the prophylaxis or treatment of of arthritis, cardioyascular. diseas. es, diabetes, renal failure and particularly eating disorders and obesty, i 7 Objects of the present yvention are the compounds of formula I and their aforementioned salts'and strs : p. rseand their use'as'therapeutically active'substances &- process for-tSe~rnámifastur-é bf t : heasåid co « poundsG Zitermediats pha in-aeiticål ~ 6, process for-th'e-ihatiafa : cti' salts and-esters, 7thre~7llme » c} ie+ couiprou-nds, esters ; ån<&7sálts7for thë~prophylåxís and/or therapy of illnesses,-esp#d : y. lm thtetreåtnient lòrpròphylaxis-of-arthritis ucardiovåscular diseases, diabetes, renaliture' (and particularly eating'disorders such as hyperphagia and particularly obesity, and the ßsé of thë said compoünds, sålts ånd ésters for the production of medicaments for the treatnient or prophylaxis of arthritis, cardiovascular diseases, diabetes, renal failure aridXlariy eating disorders and obesity.' ,..... In the present description. the term", alkyl", alone or in combination, signifies a 'Alt, i.; i ", a ttv'!'plv a+3i. , Hair t :. yl.-. , t. Wt° , straight-chain or <-t.. !'./ :-. ;-/ o Pi 7. > xi t t 7>. 1 t r. 7 9 ; eQ ; 7, S. Å !., f.. 87 i 7 straight or branched-chain alkyi group with 1 to 8 carbon atoms, preferably a Y g ,,. p Y 1 ?. . : d. Y ! -"rJu r, . t : i. 5ei, " T . ty : :,, j, 2r-y,'', i -. t.. i !-,, r ;. :, r :, a.-.,,,.., a straight or branched cham alyl group with 1 to 4 carbon, 1 atomsAExamples of strarght- '"''''-"i. j ;. t : i''-5''''''. '''''. ..-.-. .,..-.,,.,. <- : :..-. a straight or branched-chainl alkyl group with 1 to 4 carbon atoms Examples of straight- . _ y... s r F . 3 r. u'." _ 1...'... ; , ; ^--., f : .,, :..,. 3 t_' ;,.., . s. r . .. : tert.-butyl, the'isomeric, penls, the isomeric hels, the isomemc heptyis and the isomeric .. . ; az ; a.. ., ;, _. :, 4,.-. W, _..., octyls, preferably methyl and ethyl and most preferred methyl. The term bhe'or'in com ring with 3 to 8 carbon atoms and preferablyjcycloalkylringwith 3to atoms. Examples otCg-Cg cycloalkyl are cyclopropyl, ethyl-cyclopr6pyl, dimethytcyclopropyi, cyclobutyl, methyl- . : ,.. cyclobutyl, cyclopentyl, methyl-tyclopentyl, cyclohexyl, methyl-cyclohexyl, dimethyl- S. V. Y .,. : °' a,, iu1' ('...,. t...'. T'", :., cyclohexyl, cycloheptylsand ccloactl, preferablycyclopropyl : ; , t,.. : . 1.. ;...,,...,.,.. : a,.... .... _,. . _. The term"alkox", alon'e orurivcombination, synfxesra group bf the rrriizla lky'l=, 0-in which the term''alkv'l. hathe'previ

s ethoxy, n-propoxy, isoproppxy ; n-butoxy, isobutoxy, sec. butoxy and tert. butoxy, 2- . , a. : ; : :, hydroxyethoxy, 2-methoxethoxypreferably methoxy and ethoxy. and most preferred methoxy. ne or in com p I'fo'ula'aryl-0- The term"aryloky', alonie or in combination, signifies a group of the formulaaryl-O- in which the term"aryl"has the previously given significance, such as phenyloxy. The term"aryl", aloiie ör in combination, signìfies a phenyl or naphthyl group, p preferably a phenyl group which optionally carries one or more substituents each ! independently selected from halogen, frifluoromeSiyl, amino, aHyl, alkoxy, alkylcarbonyl, cyano, carbamoyl, alkpxycarbamoyl, methylendipxy, carboxy, alkoxycarbonyl, aminocarbonyl, alkyaminocarbonyl, dialkylaminpcarbonyl, hydroxy, nitro and the like, such as phenyl, chlorophEyl ; trifluoromethylphenyl, chlorofluorophenyl, aminophenyl, methylcarb'onylphenyl'nlethxyphenyl niethylehdioxyphenyl,-1-naphthyl'an. ; "''' naphthyl. Preferred is pel"3-chlòrophenyl, 3-trifluoromethylphenyl, 3-aminophenyl, .,. ..,,, : 4-methylcarbonylpheny, l, 4 methoxyphenyl and particularlp phenyl., The term"aralll",'alorie. r=in'aombination, signifie : an : alkl or cyclalkyl. group as previously defined in whichipne hydrogen atom has. been replaced by an aryl group as previously defined. Preferred benzyl, benzyl substituted with hydroxy, alkoxy or P Y, ;. ; y.. '. Y, xY XY halogen, preferably nuorme. Particularly preferred is benzyl. The term"heterocyclyl",'alone or in combination, signifies a saturated, partially unsaturated or aromatic . ta 10=menibered=Heteroccl ; e : which containS : one o. iriore, preferably one ore twõ<3x1rts sel-ectëd : frorjnitrLõgénioxygén ränd sulfut theerêîn ;. t, ;.,. : oxygen and particularly mtrpgenreprerredId more carbon atoms by'hdpgen ;-aHI,'aIkox, px'""' trifluoromethyl and'hetrocyelyl,. pre&rably Mo'rpholinyl'and pyrYolidinyl, and/or on a secondary nitrogen ato} m (z e -NH-) by a ; kyl, cycloallcyl,, aralkocarbonyl ; allcanoyl, phenyl or phenylalkyl or on a tertiary nitrogen atom (i. e. =N-.) by oxido, with halogen, alkyl, cycloalkyl and alkoxy being preferred The term-"heterocyclyl"also includes the term heteroaryl. Examples ofheterpcyclyl groups are pyridinyl, pyrrdlidinyl, piperidinyl, morpholinyl, piperazinyl, 3, 4~ dihydro-IH-isóquiholinyl azepanyl tetrahydrofuranyl and thiophenyl, wherein each ofhese rings can, be. substitutedbyone :. ormore, preferably one or two substituents independeBLy. selectedn'pm alkyl,. aHkoxyhalogen, trifluoromethyl, cyano, morpholinyl anirrolxdn ; l, P ; a ; x. ticul. rlyriprefeze. d=e, aples, o-het, erocycly are pyridinyl, pyrrolidinyl ylAhiophayl-.,,.-,, t-et-rahydro-f-uranyland furyl, wherein each of these ri/rl sY ptiRnpllytsub$titutied ; i h qne, or Biore, preferably one or

two substituents selected from alkyl, alkoxy, halogen, trifluoromethyl, cyano, morpholinyl and pyrrolidinyl. The term"heteroaryl", alone or in combination, signifies aromatic 5-to 10- membered heterocycle ; *WQontains one or more, preferably one or two hetero atoms selected from nitrogeii ;,-oxygerY and. s'últur, wherein iiitrogen or oxygen are preferred. If desired, it can be substituted, on. one or more carbon atoms by halogen, alkyl ; alkoxy, cyano, haloalkyi, heterdcyclyl'preferably trifluoromethyl. Preferred heteroaryl. cycles are pyridinyl or thiophenyl optional. y substituted by one. or more, preferably one or two substituents independently selected from halogen, alkyi, alkoxy, cyano, haloalkyl, preferably trifluoromethyl, and heterocyclyl, preferably morpholinyl or pyrrolidinyl. The term"amino'alone : or in combination, signifies a primary, secondary oT tertiary amino group bonded via the nitrogen atom, with the secondary amino group carrying an alkyl or cycloalkyl substituent and the tertiary amino group carrying two similar or different alkyi or cycloalkyi substituents or the two nitrogen substitutents together forming a mng, _suci as, or exampe, NH2, nnethylamino, ethylarnino,,, together fbrmmgaring, snchas, rexamp. dimeth Iamino, dieth lamW o, meth 1-eth lammo J rolidins-1-lor i eridino etci, Y Y, Y Y pyr. Y P p,. dimethylamino, diethylårriinó, rnethyl-ethylaminõ, pyrro : lldiri-l-yl or piperldino etc., preferably amino, dimetnylammo and diethylamino and particularly primary amino. . d"...... The term"halogen" ; sigHi6es fluorine, chlorine, bromine or iodine and preferably fluorine, chlorine or bri3rnme.'-r- '- The term"alkenyF', alone or in combination signifies a straight-chain or branched hydrocarbonresidùe~toi#$jrH igan6tefi cAb'ondai¢d-ùtto8-, p-rfër-ablyut~toF6, ~ particularly preferred up4'carbon atoms :''Examples'bfalkehyl'grdups are'ethenyl,' !- propenyl, 2-propenyl, isoprepenyl, *l'-butenyl 2-butehyl,'3-butehyl and isbbutenyl. Theterm''"aMnyrjone6riheon hydrocarbon residue conipnSingc hydrocarbori résidúe c0+3+ cå cárbon-trìpl. éXbònd bd up to 8, preferably up to 6, particularly preferredpsto 4 : rcarb : on atoins EXample, s'of alkiriyl ; groups are ethiriyl, 1- propinyl, 2-propinyl, l-biitlnyl,'2-bütinyl and 3-butinyl. . :. ' ; yta. F : =q.. =.,.,. !.,..,...,. r w : W',,....,. ; <. x,-. The term"carboxalone. pr in combination signines the-COOH group. The term"carboxallclg'z alone or'i'n. combination signifies an, alkyl group as defined before, wherein one ox, more, kprferablyane hy. drogen., atom, i. repla, ced by a carboy group. An example is carboxymethyl. ,",. . ; ; : a : Y

The term"hydró*'? åliorie or in combinåtion sig-nifies an alley ! group as define before, wherein one or mor, e ? preferably one hydrogen atom is replaced by a hydroxy efe rogen a s group. The term"aryloxy", alone'or. in combination rsignifies. the group aryl-O-., wherein the term aryl is defined as _. : i.,. :,. :. :, :.,.....,, :,, ;..,. The term"cyana'aldrie. or in combination signifies the group-CN. alone of in coriibintion'signifies the group heterocyclyl-O-, whereinathe terrn heterocyclyl is defined as before. ... _,. ;.,...... :.,,,., :,, The term"actetylarmnio", alon or in coriibination signifies the group =NH-CO-CF-I3. The term"actetylammo", alone or in combination signifies the group-NH-CO-CHg. a] Wrl g s j, ; v" n spi , vt. i., m .. 'v (N".,'nf : i, E'i ;-i. : y. -s5 : , .. ;.. r. ,, :. 'ti.,,... _ acryl,,, acryl wherein the term aryl is defined as before and, wherein both aryl groups are the same or are different. . s', (i° :''.,.,..,, ;..,.... . -.,. The term"heteroarylamino", alone or in combination signifies the group heteroaryl- NH-or , ;, i u. k,, ,., . ;. he't'er''o"a' ......, . 3 t, .. 1 .., YEh ,. ^. _ ... wherein the term heteroaryl is defined as before and, wherein both heteroaryl groups are ., .,,. :.. a..,. ;,. the same or are differerit .,.... .. The term"pharma. eeutieally acceptable salts"refers to those salts which retain the . ; t 1 X ;' biological effectiveness and properties of the free bases or free acids, which are not biologically or otherwise undes*able. The salts are formed with inorganic acids such as hydrochloric acid, hydro$romi'acid, sulmric acid, nitnc acid ; ph acid and the like, preferably hydrochloric acid, and organic acids such as acetic acid, propionic acid, glycolic acid, pyrumc acid, ; q'xylic acid)., maleic, acid, : malo succinic acid, fumaric .,, : >. ...- ;., _,.... _.,.. acid, tartaric acid, citric acid, benzoic acid, cinnamic. acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-tQluenesulfbhic'a'cid, salicylicacid, N-acetylcystein and the

like. In addition these salts be prepared form addition of an inorganic base or an organic base to the free acid. Salts derived from an inorganic base include, but are not limited to, the sodium, potassium, lithium, ammonium, calcium, magnesium salts and the like. Salts derived from organic'bases include, but are not limited to salts of primary, secondary, and tertiary amines substituted amines including naturally occurring substituted amines, cyclic amihe and basic ion exchange resins, such as isbprbpylamine, trimethylamine, diethylaminc, triethylamin : e,'tripr6pylamihe, ethanolamine, lysihe, arginine, N-ethylpiperid piperidine, polymine resins and the like. The compound of formula I can also be present in the form of zwitterions. Particularly preferred pharmaceutically acceptable salts of compounds of formula I are the hydrochloride salts. The compounds of formula I can also be solvated, e. g. hydrated. The solvation can f. g rs be effected in the course of the manufacturing process or can take place e. g. as a consequence of hygrosc. op, ic. properties of an initially, anhydrous compound of formula I c"'> ß5, tst t ; ! ltl. -, a7-ìrr :''. tit. $ 7TS ! ts yDf (hydration). The term pharmaceutically acceptable salts also includes physiologically zu usablesolvates ~ itjS. s"< ; r è5 r usable solvates.- 'TharmaceuticaUyidcctable'ester may be derivatised at'fuSetiohal'grbups'to'prdvide derivative hich are capabld'of un s-inyi 6 conversion back to the parenoinpoundsih'yivd. : ..,,,.,... physiologically acceptalzl andeirietabolically labile °eser derivatives ; such as ;"¢' methoxymethyl esters, methylthiomethyl esters and pivalpyloxymethyl esters. Additionally, any physiologically acceptable'equivalents of the compounds of general formula (I), similar to the metabolically labile esters, which are capable of producing the parent n.. y,. : 11t-. F,,.. : r. compounds of general forinula, (-L) in vivo, ; areiminft invention. ;- t yee,. ,. (. S ; 7i, , ! 1 : dn, ? Tt. .. : . ;) il. r--rryals :. t_..... t'^.' ; F u ? : i t''"T'.".,'t.. : ; The term"lipa : sehlbit'" ! : efers to ; cdmpoundsMh are c the action of lipases, for example gastric and pancreatic lipases. F, or example orlistat and action of lipases, for eaznple gastric and pancreatic lipases F. or example orlistat and lipstatin as described in U. S.. Patent No. 4,598,089axe p. otent nhzbitor of lipases. Lipstatin is a natural product of bial origin, and orlistat is the, result, of a hydrorenation of is a natural product of microbial origin, and orlistat is the result of a hydrogenation of lipstatin. Other lipase inhibitors include a class of compound commonly referred to as . ; r--_,, : ..,,.,,. . :.. _.,..,.. panclicins. Panclicins are analogues of orlistat (Mutoh et al, 1994). The term"lipase inhibitor"refers also to polymer bound lipase inhibitors for example described in International Patent Application W099/34786 (GeltexPharmaceuticals Inc.). These polymers are characterizeid infthat they have been substituted with one or more groups that inhibit lipases. Thç>terrn''lipaselinhibitor"also cornprises pharmaceutically acceptable that inhibit lipases. Th, tqml* salts ofthese compoun. terrnAmWo,';. EçfèFai : iy refes to orlistat

Orlistat is a known compound useful for the control or prevention of obesity and hyperlipidemia. See, U. S. Patent No. 4,598,089, issued July l, 1986, which also discloses processes for making orliståt ánd U. S. Patent No. 6,004,996, which discloses appropriate pharmaceutical compositipns. urther suitable pharmaceutical compositions are described for example in Inter. Patent A*plications WO 00/09122, andWQ 00/09123. pQO/, 09112Z-aix4.. WQ. 00/09123. Additional processes for the'preparation of orlistat are disclosed in European Patent Applications Publlcåtilion N'6-"'§' Orlistat is preferably orally administered from 60 to'726 mg per day in divided doses two to three times per day, Preferred is wherein from 180 to 360 mg, most preferably 360 mg per day of a lipase inhibitor is administered to a subject, preferably in divided doses two or, particularly, three times per day. The subject is preferably an obese or overweight iass index r human, i. e. a human with atbpdy mass index of 25 or greater. Generally, it is preferred that the hpase mhlbitor be administered within about one or twò hours of ingestion of a meal ...,. , s...... Te. t. y, j,. y t,. j,, r ; -. j... i, ipCt-.. :, l : e ; i', ", : <t.. :. containing fat. Generally, administering a lipase inhibitor as denned above it is preferred that treatment be administered to a human who has a strong family history of ,,, ;,,.".,.... obesity and has obtained a body mass index of 25 or greater. -, i= : ;..., > :..,...... _..., Orlistat d conventional o compositions, such as, tablets, coated tablets, hardand soft gelatin. capsules, emulsions or suspensions. 4slls, S; l Examples of carriers which can be used for tablets, coated tablets, dragees and hard gelatin : capsules are lactose, other sugars and sugar alcohols like sorbitol, rnannitol, maltodextrin, or other fillers; surfactants like sodium lauryle sulfate, Brij 96, or Tween 80 ; disintegrants like sodium starch glyclate,. maze starch or derivatrveseth, ereof, polymers lke. povidone, 1,'. st . :' _..,. r,, 4r-_ r. »- .. _ ;,. ; :-. ... crospovidone ; talc, stearzc acicior its salts and th like. : Smtabe carriers for. soft gelatin ,,, r. , , _ ;.,.,,,... r. ., ; ;.. a..' : capsules areSfor exampfle ? yegertable ollsi wases, fats, semi-solid-and liquid polyols andRe like. Moreover, the pharmaceutical preparations eanGontainpreserving agents, : P t, r :. P l ?.. : Px.... g g solubilizers, stabilizing, agents. westing agents, emulsifying, agents,, sweetening agents, coloring agents, flavoring agents, salts for varying the osmotic pressure, buffers, coating agents and antioxidaXits. >. catn also contain stB otlier therapèùtically valuable substances. The formulations. ; may coyeniently be.. pres. ented in ; unit dosage form and. may be prepared by any met, h, odsPiaowniin the phiarmaceutical art*-Preferably, orlistat is administered accordirto, e : ; for ; mulation shownin, the Examples. ndin U. S. Patent No. 6,004,996, respectively.,.. .. : : . .,.... - :'°. I_, ;.'} .. '.,..-.. The compounds. pifprmul. a J can. contain several asymmetrie centers and can be present in the form of optisallypure. enantiomers, mixtures of enantiomers sucli a's, for

example, racemates, optically. pure diastereioisomers, mixtures ofdiastereoisomers, diastereoisomericracemtes, pr mixtures of diastereoisomeric racemates. ,., i, fs ^,,'... .'.,.'Ea. _,... _.... In the nomenclature used'm the present description the ring atoms of the quinoline ring are numbered as follows, * ring are numbered as follows :"' 3è t 5 4 "''""."'''"8 yj ? y Preferred are compounds, of the formula I, wherein 8 ., : °., ;- :,,',., 1.,.. :.'. s,-, y.'.,.,. Preferred are co, mpounds : of the formula I, wherein :. Rl is hydrogen,. alkyl, alkoxyalkyl, alk,, en. yl,., alkinyl, hydsox, y, alkyl, ar$: alkyl,,, heterocyclylalkyl, cycloalkylalkyl, NI3a S02 ; monoalkylarnirio=SOZ= ; dialkylaniino-SOZ-oryalkyl-SOZ- ; ..., rpi^,. , ='".. A.. t. .' t, e, "a, te k't-t....,,...'^e. n.,.'j 1. . : li. teg. Vl.. ltf"j c 7t.. _... SiG1 :" ! ; _ i is hydrogeri"halogenlWnyl, alkinyl, aralkyi, heteroaryl ; affiyl, hydroxpallg alkoxy, alkoxyalkpxy,''hydroxyall< : oxyalkyl, aryloxy, arylamino, heteroarylamiho, NH2-, mono-or dijalkylamino, heterocyclyl, arylalkylamino, heteroarylalkylamino, Y, y. Y. ;. '. Y rY'.. ; :, ,,, y.,.. 3 : :, F,. aryl, heteroaryl, arylalkpxy ojr heteroarylålkoxy,... R3 is hydrogen, alkyl, NH2, yorioalkylamino, dialkylainino or alkoxy ; R4 is hydrogen, alkyl, alkoxy, hydroxy, NH2-, monoalkylamino, dialkylamino, acetylamino orcya-po-,, R'is hydrogen-,,- -a'-n't-''-- s u nol R5 iS hydrogen ;-;'tt<t f¢tì,, a-le a. & g v_a w tY" : C. ^,.'..'. t>ph, r,,, : a as :.. _ A is a saturated ring consistmjtoa nitrogenatomvvhichvis ached to the quinolirie ririg'' and a'- (CH, n being 4,5, or 6 ; .,g,. EA',. !, u....... and pharmaceutically accàlle salts and esters tliereof. r :.,,.... . : t , ;.,. 4. Preferred compounds of ifòrriiulå I åre thosé, whérein Rl is hydrogen, alkyl, aLkenyl, hydroxyalkyl, aralkyl, heterocyclylalkyl, cycloalkylalkyl ; dialkylamino-S02-, alkyl-SOa-, dialkylaminoalkyl, alkoxycarbonylalkyl, aryl-SO2-O-alkyl or cycloalkylalkyl. r. 2 ?. r. ~ ~ a In a further preferred embodimentÆofkthe itnvention Rl is hydrogen, alkyl, 77 alkoxyalkyl,, alkenyl, alkuyl, hydroxyalkyl, axalkyl, heterocyc ylalkyl, cycloaalkylalkyl NHZ-, , .. t,., 9. c. t..... pt.., u r : t s 1 y a. : t ay. -k. I t.., . . _. mono-or dialkylammo OZ, ox alky, l SOZ. rA furtherpreferred embodinrent of the.., present inyention Rl is C) laX ärb orG hetgroarAyrlakl. *er

preferred are compounds according to formula (1), wherein Rl is hydrogen, aralkyl or heteroarylalkyl. Particularly preferred are compounds of formula (I), wherein Rl is hydrogen, phenylalkyl or pyridinylalkyi wherein the phenyl-and the pyridinyl cyles are optionally substituted with one to three substituents independently selected from the group consisting of alkyt ty, cyano, or halogen, preferably, methyl, alkoxy, cyano, or halogen. Further particularly preferred are compounds, wherein Rl is hydrogen, cyclopropylmethyl, (methbxyphehylmethyl, (eyanbphenyl) m pyridinylmethyl, (fluropyridinyl) methyl, (chloropyridinyl) methyl, or (methylpyridinyl) methyl. Very preferred are compounds, wherein Rl is hydrogen, cyclopropylmethyl, (methpxyphenyl) methyl, (cyanbphenyl) methyl, (chlorophenyl) methyl or pyridinylmethyl. Particularly preferred are compounds of formula I, wherein Rl is hydrogen, cyclopropylmethyl (methoxyphenyl) methyl,. (cyanophenyl) methyl, (chlorophenyl) methyl, ? yidqinylmiethyl chloropyridi tnylmethyl, or fluorppzzridinylrnethyl. 5 ,.. 5t ; 31f. 7.. i"; 2 ir In a preferred present of the present invention R is hydrogen, halogen, alkyl, ,.. a,.. .... : r. p. ; _ . _,.......,.,.. alkenyl, alkinyl, aralkyl, heteroarylalkyl, hydroxyalkyl, alkoxy, alkoxyalkoxy, hydroxyalkoxyalkyl, aryloxy.'arylaminp, heteroarylamino, NH mono-or dialkylamino ,''? j'T 7S, S S T < S t ? t T S k ; g,, u Ho {S s 2 a rt or aryl (alkyl) amino. In anpther preferred embodiment of the invention R is hydrogen, alkyl, or halogen. Particularly preferred are compounds of formula (I), wherein R2 is hydrogen. Likewise preferred are compounds according to formula (I), wherein R is alkyl. Other preferred compounds of formula (I) are those, wherein R is hydrogen, butyl, fluoro, chloro or bromo. Particularly preferred are hydrogen, butyl, nuoro orbromo. n Ie co m-p o un--d A preferred aspect of thejpresentinventibn'arecompound formula I, wherein R is hydrogenkyly. aiko, heter, m6np- ; ordialkylaminb. Further preferreid compo, unds sf formula (I3r are thoses wherein R3 is hydrogenj alkyl, or s n- _'. :, NH2-. Preferred comppundare those, wherein is'alkyi, particularly methyl.. ; "A, _,. _ ;, ... ., <.. 3, Preferred are combpbusidsiof formulå I, wherein R4 is hydrogén, allçyl, cycloalkyl, cycloalkyl, alkoxy, hydroxy, monoalkylammo, dialkylammo,, hdroxyalkyl, alkoxyalkyl, cycloalkory, alkoxy, cycloalkylalkbxrheterocyclyl, heterocyclylpxyalkoxy, hydroxyalkoxy, ,.,.,.,.. alkoxycarbonyl, hetero+l or älkyl-tSO2-. t 4 alkoxycarbonyl, heter't" ? if Akl ;-'S02"- , : er°. e. r ; r i.,,,., In a preferred embodim ! entoftheinYentiQn, R alkpxy ;. Another preferred aspect of the preseiit irivention are cozripoii'iids°of forriaula (I), wherein R4 is hydrogen or alkoxy. Parti'<arly preferred compounds those, wherein R is hydrogen, alkoxy, alkpxy'alkyhydroxyal] l'or''hydrbx

Further preferred are those compounds of formula I, wherein A is a 5-to 10- membered mono-or bi : cyclic saturated heterocyclic ring comprising the nitrogen atom which is attached to the quinolirie ring and optionally one or two further oxygen atoms. Preferred compounds accdrdmg to formula I are those, wherein A is pyrrolidinyl, azepanyl, morpholinyl, l,,, 4-dioxa-8-aza-spiro (4.5) dec-8-yl or piperidinyl. :. ; Other preferred compounds of formula. (I) are those,, wherein A is a pyrrolidinyl or azepanyl ring. Particularly preferred is a pyrrolidinyl ring. Preferred compounds of formula I are those, wherein R is hydrogen. jt ^," Examples of preferred compounds of formula (I) are 1. 7-Benzyloxy-2-methylpyrr61idin-l-yl-quinoline ; 1.7-Benzyloxy-2-methyl 4 pyrrolidin-1-yl quinoline; 2. 7-Benzyloxy-2-methylXpyrrolidin-i-yl-qüinoiirie, -ru.,.2-Methyl-4-pyrrolidii' in- 3. Dimethyl-sulfamic acid 2-methyl-4-pyxrolidin-I,-yI-qmnolin-7-yI ester; s.. i. s '°' e :. ='o'v. s--.,, r-rs ;,. 4. Methanesulfonic acid 2-methyl-4-pyrrolidin-l-yl-quinolin-7-yl ester ; ,, r ; , ;, , ; ;, ; :.,....,, ;.. 5. 7-CyclopropyImethoxy2-methyl-4-pyrrolidin-1-yl-quinoline ; 6. 7- (3-Methoxy-benzyT6) 2'-methyl-4-pyrrolidihl-yl-quiholine ; .,.. ;. 4o",.. 7. 7-Methoxy-2-methyI-4pyrrolidin-1-yl-quinoline ;. : ... 8. 2-Methyl-7- (pyridinyinieth6xy).- sA-... 7-7-MethOxwr-2-methyi-e yìrö-dE-I-yl-quinolirle ;. ~~.. 9. 7-AUyloxy-2-meinpyrMidinl =''''""'--" v,.,.. ;. , » , t. ci :,. ; a.-, _,, _ _ e-''°'.. 9. 7-Allyloxy-2''metl'iyTtg ri3'31t yl~-quinÖ e f.',.,,'I K-r 10. 7-Isobutoxy-2-mewr&ìdin-1-yL-quinQlinèi ^ Q -quino me; 10.7-Isobutoxy-2-rnetli,-!,"4 11.7- (2-Methoxy-benzylóx 2 f methyl-4-pyrrolidin-1-yl-quinoline ; . 12.2-Methyl-4-pyrrolidi-ylA7- (tetrahydro-furan-2-ylmeths oxy)-quinoline ; .,,-,. 13.7-(4-Methoxy-benWyj-9-methyl-4-pyrrolidm-I-yi-qùinoline ; ..''r.''''.'. 14. 2- (2-Methyl-4=pyivolidiri y-yl'quirioTiii=7=ylo'Xyniefihyl)-benzonitrile ; 15. 4- (2-Methyl-4-pyrolidl,..,.,. ,.,,., , j,-.... _,,. ;,.,. : 16. 2-Methyl-4-pyrrolol. im il', y-7 (2-trifluoroiiietliyl=lierizylory)-quinoline ;

17.2-Methyl-4-pyrrolidin-1-yl-7-(3-trifluoromethyl-benzyloxy )-quinolinei 18.2-Methyl-4-pyrrolidin-1-yl-7- (4-trifluoromethyl-benzyloxy)-quinoline ; 19.7-(2-Chloro-benzyloxy)-2-methyl-4-pyrrolidin-1-yl-quinoli ne; ,,,,... t. 20.7- (3-Chloro-benzyloxy)-2-methyl-4-pyrrolidin-1-yl-quinoline ; 21.7-(4-Chloro-benzyloxy,)-2,-, methyl-4-pyrrolidin-1-yl-quinoline; 22.2-Methyl-7- (pyridin-3 ylmethoxy)-4-pyrrolidin-1-yl-quinoline ; 23.3- (2-Methyl-4-pyrrolidin-I-yl-quinolin-7-yloxymethyl).-benzoni trile ; 9,, hvl),.-benz. on rile; 24. 7-Isopropoxy-2-metliyl 4 pyrrolidin-1-yl quinoline ;. ,, .,, ; :.,..... 25.7- (2-MethoXy-ethoY 2 methl--, pyiioidm'lyT-qumoline," ,. : -h,,"ih''ifiol* 26. 2-Methyl-7- (2=inorpiolm 4=y etlioX'y j=pzrolidiii=l. yl-qiiiriIine ; . t- ; ,..,,...,. 27.2-Methyl-7-(pyridivioxy)-4-^p'yrroli'din-1-yl-'qulnóiine ; 28. (S)-'7-Benzyloxy 4- (3TefhoXy-pyrrolidin-1-yl)-2-methyl-quinoline ;,." 29. (S)-4-(3-Ethoxy-pyWin'''l-yl)-2-methyl-quinolin-7-ol ; 30. (S)-4- (3-Ethoxy-poMn-i-yl)-7- (3-methoxyenzyloxy)-2-methyl-q 31. (S)-4- [4- (3-Etho+ din-1-yl)'-2-Inethyl-quinoiin-7-yloxymethyl]-benzonitrile ; 32. (S)-2- [4- (3-EthopyrroMinf-yI) me-benzonitrile ; , a. ^.,, y ; i t 33.7-Benzyloxy-6-4pEri'ólids yt-q=4i s} _ i i i'''' 34.6-Butyl-4-pyrrolidm"z yl quiiiolin-7-ol ; 35.6-Butyl-7-methoxy 4='pprrolil. in-1-yl-quinoline ; ....... 36.6-Butyl-7-ethoxy-4+n-i-yl-quirioline ; 37.6-Butyl-7-cyclopropWhòxy-4-pyrrólidin-i-yl-qüinolinei ! w 38.4- (6-ButyI-4-pyiroli3in% "'' ine,. 39.4-Azepan-1-yl-7 beiizyl'oxy,, 2, riiethyl quinoline,'. 5'.,'. ;-,.-.

40.4-Azepan-1-yl-2-niethyl-quinolin-7-ol; 41.4-Azepan-l-yl-2-methyle7-(pyridin-4-ylmethoxy)-quinoline; 42.4-methyl--quinolin-7-yloxymethyl)-benzonitrilei.. 43.3- (4-Azepan-1-yl-2-methy-quinolin-7-yloxymethyl)-benzonitrile ; ? ;- 44.4-Azepan-l-yl-2-methyl ; t (pyridin-2-ylmethoxy.)-quirloline ; r... 45.6-Bromo-7-methot-4-pyrrolidin-l-yl quinoline ; 46. 6-Bromo-2-methyl-4-pyrrolidin-1-yl-quinolin-7-ol ; : ,,, 47.4-(6-Bromo-2-me-pyrrólidin-1-yl-quinolin-7-yloxymethyl)- benzonitrile; 'f e, '^,. 1,,'v'-...,, 7. ? ;. 49.7-Methoxy-4-pyrrol-1-yi quinolin-2-ylãrnine ; ~ 50.4-pyro 50. 4-Pyrrolidin-l-yl : eO J ? t, 0 irt) ' 51.7- (3, 5-dimethoxyB2ylpxy)-2-methyl4-p y, lo ] l ol 52.7-(3, 4-dimethoxy-benWy)-2-mèthyl-4-pyrrolidin i-yl-quinoline ; 'y 53. 7-ethoxy-2-methy ; rHfilidin-1-yl-qüinolinei.. 54.2-Methyl-7- (6-metiiypyrMin3-ylm -pyro6 55.2-methyl-7- (2-methyl==pymdin-3-ylmethoxy)-4-. pyrrolidin-1-yl-quinoline ; 56.7-(6-chloro-pyridXxy)-2-methyl-4-pyrrolidin-í yl-qúinoline ; v, t : v''.,',.,.-, ; y 57.7-(2-chloro-pyridin) yt thòxyj-2-methyl-4-oín-l-yi-qüinoline ; 58.7-(2-fluoro-pyridm i ioxy)-2-methyr-4-pyrroiidin-i-yl<-qúinoline ; yo 59.7- (2-cMoro-6-metRyIyridin-3-ylmethoxy)-Ym 60. 7-(2-chloro-6-triflkoriopyridin 3-ylmiedloxy)-2-methyl-4-pzyrrolidin-1-yl- quinoline ; 61.5-(2-methyl-4-pyrr. nv yl-quinolin-7 yloxymethyl)-pyridine-2-carbonikile ;

62.7-(5-chloro-thiophen 2@1wóxy)-2-methyl-4-pt olidin-l-yl-quinolinei 63.2-methyl-4-pyrrolidin-1.-yl-7- (thiophen-3-ylmethoxy)-quinoline; 64.4- (2-methyl-4-pyrrolidin-, 1 :-yl-quinolin-7-yloxy)-benzonitrile; Y, 65. (S) 4- (3-ethoxy-pyrrolildin-1-yl)-7-(2-ffuoro-pyridin-3-ylmethoxy) -2-methyl- quinoline ; 66. (S) 7- (2-chloro-pyridin-3-ylmethoxy)-4- (3-ethoxy-pyrrolidin-1-yl)-2-methyl- quinoline ; 67. (S) 4-(3-ethoxy-pyrrolidin-1-yl)-2-methyl-7-(pyridin-3-ylmethoxy )-quinoline ; i r : ja ? Y, rj rrx. r7 ; t í'''~ ;. ire ;' 68. (S) 5-F4-(3-ethoxy-pyrrölidin-1-yl)-2-methyl-quinolin-7-yloxyme thyl]-pyridine-2- carbonitiil, e ;-,,,- 69.4-azepan-1-yl-7- (-3-meo-benzyloxy)-2-methyl-quinoHne ; 70.2- (4-azepan-1--yl-2 m,'e, thyl-quinolin=7=yloxmethyl) benzonitrile ; . 71. 4-azepan-1-yl-7- (3-chloro-benzyloxy)-2-methyl-quinoline ; 72. 4-Azepan-l-yl-7-(4-cKlororbenzyloxy)-2-rnethyl-quinoline ; 73. 2-methyl-7- (6-morphQlin-4-yl-pyridin-3-ylmethoxv)-4-pyrrolidm-l-yl-Quin olme ; ..,, c . f :',.. a _..-y2r,"'1. : n..,,, q rp. r 74. 2-methyl-4-pyrrplidin'-yl. 7- (6-pyrrolidin-l- .. _, i y S, T. .. n _, i.,.. 75. [2,2-dimethyl-3 (2-my4-pytrolidih-l'- amine; , Y 76.2-methyl-7- (l-methylpiF'endm-4-yloxy)-4-pyrr. olidm-I-yl-quinolme ; ,.,,,. ..,,. 77. 2-methyl-4-pyrrolidin-1-yl-7- (tetrahydro-furan-3-yloxy ?-quinoline ; 78. 2-Methyl-7-(l-mevèridin-4-ylmethoxy)-4-pyrrolidin-l-yl-quin oline 79. 2-methyl-7- (3-morpholin-4-yl-propoxy)-. 4-pyrrolidin-l-yl-quinoline ; 80. (2-methyl-4-pyrrolidt. n. 1, quinolin-7-yE aseeethylester, ,...'. t. ifr,...... 81. 2- (2-methyl-4-pyrroydin l, yl-qu, yolin-7-ylo, )-ethanol,. A :,. a.-. _ _

« 82. toluene-4-sulfonic aicid 2-(2omethyl-4-pyrrolidin-1-yl-quinolin-7-yloxy)-ethylester; 83.2-methyl-7- (3-pyridin 2-yI propoxy)-4-pyrrolidin-1-yl-quinoline ; 84.7-benzyloxy-2-metHyI-4iSrpholm-4-yl-quinoline ; , nprp o in 85. (S)-I- (7-benzylox-_''-"1-, in . . . 86. (R)-1-(7-benzyloxy ; 2-methyi-quinoliii 4-yl ?-pyrrolid-în-3-ol ; ~~ . :. :, ;,,,. 87. (S)- [1- (7-benzyloxy 2-, methyl-quinolin-4-yl)-pyrrolidin-2-yl]-methanol ; ..,, .',..... 88. (S)-7-benzyloxy-4-(2-mSthoxymethyl-pyrrolidin-1-yl)-2-methyl -quinolinei. t 89. (S)-4- (2-Methoxymetliyl pyrrolidin-1-yl)-2-methyl-quinolin-7-ol ; 90. (S)-7-(2-chloro-pynSin-+eiöxy)--4-(2-$rnëxy4xzrölidin-1-y l)-2- y. methyl-quinoline,. a, ...,. 91. (S)-7- (2-fluoro,-pyridi. n 3-ymethoxy)-4-2 methoxymethyl-pyrrolidin-1-yl)-2- methyl-quinoline ; methyl-quinoline ; 92. (S)-7-cyclopropylmethoxy-4-(2-methoxymethyl-pyrrolidin-1-yl) -2-methyl-quinoline ; 93. (S)-4-(2-hydroxymethyi-pyrrolidin-1-ylj-2-méthyl-quinolin i-ol ; ,, t.. , : ; Y,,, z,.,, 94. (S)- {1- [7- (2-fluoro-pyridin-3-ylmethoxy)-2-methyl-quinolin-4-yl]-pyrro lidin-2-yl}- methanol; methanol ;-i Znr W r"; r,... 95. (S)- I- [7- (2-1 pyrrolidin-2-yll- OXY méthanol- 96. (S)-2- [4-. (2-hpdroxymethyl , yrriadm'1-3I Z., ne'ChI qmiioliw-7-yloxymethl]- benzonitrile ; ., R ; 96. (S)-2-[4-(2zll1da ttnolin-7-yloxymethyl]- benzonitrile ; i ;.. 97. (S)- {l- [2-methyl-7- (pyridin"3-ylmethoxy)'-qumolm-4-ypyrrolidm-2-yl}-methanol ; '., w>.,,..,, . ;...... 98. (S)-5-f4- (2-hydroxy ! NetlpyrroIidin-l-y !)-2-methyl- pyridine-2-carbonitrX ut 99.7-benzyloxy-6-uor : eanië. thyl-4-pyrrolidin-1-yl-quinöline ; 100. 6-ffuoro-2-methyl ; 4- : pyrrlidim l=yr-quinoliri=-tl ; rvz -

101. 4- (6-fluoro-2-methyl-4-pyrrolidin-1-yl-quinolin-7-yloxymethyl) -benzonitrile ; a,"° y- ; , s 102.6-fuoro-2-methyl-7- (pyridin-3-ylmethoxy)-4-pyrrolidin-1-yl-quinoline ; ion 103.6-Buoro-7- (2-Budropyiidin-3-ylmethbxy)-2-methyl-4-p 104.7-(2-chloro-pyridin'3''ylmethoxy)-6-fluoro-2-methyl-4-py rrolidin-1-yl-quinoline; 105.6-fluoro-2-methyl>'7-(2 : methyl-pyridin-3-yIrnethoxy)-4-pyrrolidin-1-yl-quinoline ; , u ... \. 106.3- (6-ffuoro-2-methyl-=4=pyrrolidin-1-yl-quinolin-. 7-yloxymethyl)-benzonitrile ; 107.2- 1-4-pyrrolidin-1"yl quinolin-7-yloxymethyl)-benzonitrile ; 1 108.7-cycIopropylmetH6xyHubro-2-methyl-4pyrr : 109.5- (6-fluoro-2-mefhy-pyrr6lidm-'ly !.-'quiholi carbonztrile ;. a :..,,., 110. (R)-7-benzygxy-4,- carbonitrile ;. rr-."."i' ; r'"--'-"---'.--'-.... .-'.... ".-.,-'." ; n. :. f"..',"-"...-' ; 110. (R)-7-benzyloxy 44 (3 methoxy-, pyrroldin-1-. yl) 2-methyl-cuinoline ;, '... l. zi'_. 'y [.. .,.. e... n x,'i. ., 't : it : ! ..., ;. 111. (S)-7-benzyloxyi- (3-itethoxy-pyrrolidin-1-yj)-2-. Methyl-, quinoline ; 112. (S)-7-benzyloxy-4- (3-methoxy-pyrrolidin-l-yl)-2-methyl-quinoline ; '-'-'"..' ; x'i'T'-.... 113. (S)-7-benzyloxy 4 n (3 cycl, oprop, ylmethoxy prrolidin 1-yl)-2-methyl-quinoline ; j) 7 114. (S)-7-benzyloxy-4- [3- (3-iQethoxy-propoxy)-pyrrolidm- l-yIJ-2-methyl-Quinoline ; ". TOli y 115.7-benzylo-2 methyl r {3S) ; 3- [2 (tetrahydro p. yran=2-yloy).- ; ethocyJ.-prolidin- . _., _,.,. : : :. yrAr'2 y 1-yl}-quinoline ; 116. (S)-4-(3-methoxìr pyrarolidm-1-yl)-2-methyl-quinolin-7-ol ; ....,,-...... 117. (S)-4- (3-methoxy-pyr, r. blidin-1-yl)-2-methyl-qu'inolin-7-ol ; 118. (S)-4- (3-cyclopropylxnethoxy-pyrrolidin-1-yl)-2-methyl-quinolin-7- ol ; 119. (S)-4- [3- (3-methoxy-propoxy)-pyrrQlidm-l-yl]-2-inethyl-qiL [inolm-7-ol ;. , n ffi..., ;, . ; l. ",., 120. 2-methyl-4- { (3S)-3- [2- (tetrahydro-pyran-2-yloxy)-. ethoxy]-pyrrolidin-l-yl}- quinolin-7-ol ; ;,,. ; r, ; . ;, ...,.." _-'<. ,, : a quinolin-7-ol;

121. (S)-4-{4- [3-(2-methoxy-ethoxy)-pyrrolidin-1-yl]-2-methyl-quinolin-7- yloxymethyl}-benzonitrile ;' ,,.. :. 122. (S)-4-[4-(3-methoxywSrolidin-1-yl)-2-methyl-quinolin-7.-ylox ymethyl]- benzonitrile ;-U ; !. Å- A 123. (S)-4- [4-(3-cyclopr. ot pylmethoxy-pyrrolidin-1-yl)-2=methyl-quinolin-7- yloxymethyll-ben6iliti : il,"Z ! 124. (S)-4- {4- [3- (3-methoxy-. propoxy)-pyrrolidin-1-yl]-2-methyl-quinolin-7- yloxymethyl}-benzonitrile; .,,.,-, _. ; T.. 125. (S)-4- {4- [3- (2-Hydroxy-ethoxy)-pyrrolidin-1-yl]-2-methyl-quinolin-7- yloxymethyl}-benzon<i 126. (S)- [1- (7-benzyloxy-'6-fl : oro-2-methyl-quinolin-4-yl)-pyrrolidin-2-yl]-methanol ; . _ _ _. ; L. i ;. f Y ;. "r1.'".,. ) t ' ;,'. oi., s'.. leti ;. 9^ 1_ ;. ,. _ 127. (S)-6-fluoro-4-, (2 jAydjroxymethyl-pyrrolidin-1 yl)-2-methyl-quinolin-7-ol ; .. y, ;.."_ ;....... 128. (S)-4-[6-fluoro-* (! 2elWri3iXymethyl-pyTrolidinrl-yl) r2omethyl-quinolin-7-s. yloxymethyl]-benzonite, 129. (S)-5- [6-fluoro-4- ; hydroxymethyl-pyrrolidin-1-yl)-2-methyl-quinolin-7- yloxymethyl]-pyridine-2i-. carbonitrile ; 130. (S)-4- [4-(3-hydroxyripprolidín-1-yl3-2-methyl-quinolin-7-. yloxymethyl]- benzonitrile ; r,. 2 rS @ ., : f. ; ;. .. .. 131. (R)-4- [4-(3-hydroX+-pyEriblidin-Eyli+methylmuinolin-7-ylbLymethyl benzonitrile ; ~ ; 17J& ; 7 77-iiiß ; t : 132. (R, S)-4- [2-methyl-4= (2-methyl-pyrrolidin-1-yl)-quinolin-7-yloxymethyl]- benzonitrile ; 133. (S)-4- [4- (2-hydroxyinethyl-pyrrolidin-1-yl)-2-methyl-quinolin-7-yloxy methyl]- benzonitrile ; T.. r ; 134. (R)-4- [4- (2-hydroxymethyl-pyrrolidin-1-yl)-2-methyl-quinolin-7-yloxym ethyl]- benzonitrile ; ; benzonitrile ; 135. (R)-4- [4- (3-dimethylammo-pyrrolidin-l-yl)-2-methyl-quinolm-7-yloxymet hyl]- benzonitrile ;

136. (S)-4- [4-(3-dimethyláamino-pyrrolidin-1-yl)-2-rnethyl-quinolin-7- yloxymethyl]- benzonitrile ; ,, i, ; ; 137. (R)-4- [4- ! hyl-pyrrolidin-1-yl)-2-methyl-quinolin-7-yloxymethyl]- benzonitrile; , z, , ;.,,,... benzonitrile; 138. (S)-4- [4-(2-methoxymethyl-pyrrolidin-1-yl)-2-methyl-quinolin-7-ylo xymethyl]- benzonitrile ;, : :, :.-, . : ; ,.., 5.. ; .. r.... 0, |'.... 139. (R, S)-4- [4-(2-isopròpyi pyr-rolidin-1 yl)-2Lrnethyl-qúinolin-7-yloxyimethyl]- benzonitrile ; 140. (S)-1- [7- (4-cyano-benzyloxy)-2-methyl-quinolin-4-yl]-pyrrolidine-2-ca rboxylic acid methyl ester ; ; :.', ; : 141. (R)-4- [2-methyl-4- t. I J benzonitrile ; 142. amino _, r.. .... 142. (S)-4-[2-methyl. 4--: tthylamino-pyrrolidin-1-yl)-quinolin-7-yloxymethyl]- benzonitrile ; 143.4-(2-methyl-4-piperidin-1-yl-quinolin-7-yloxyméthyl)-be nzonitrile ; methyl) 144.4- (2-methyl-4-morpholin-4-yl-quinolin-7-yloxymethyl)-benzonitr ile ; 145. (R, S)-4- [4- (3-diethylamino-pyrrolidin-1-yl)-2-methyl-quinolin-7-yloxyme thyl]- benzonitrile 146. (R, S)-4- [2-methyl : 4-(3-ipyridin--2-yl-pyrrolidin-1-yl)-quinolin-7-yloxyrnethyl ]- ,..,.,. :.,., ;,..,.,,,...,. a.. benzonitrile ; ~'S 147. (R, S)-4- [2-methyl (pyridin-4-yl-pyrrolidin- l-yl)-quinolin-7-yloxymethyl]-. ,. benzonitrile ; ., ".,.'. ,. _..,,., 148. (S)-4-[2-methyl-s (Aprolidin-1-ylmethyl pyrrolidin-1-yl)-quinolin-7- yloxymethyl]-benzonitrile ; ;. r.. ;, ; ; : : ;,-_.. :..,... 149. (R, S)-4- [4- (3-methariesulfonyl-pyrrolidin-1-yl)-2-methyl-quinolin-7-ylo xymethyl]- benzonitrile ;'aV x. rr... _, :..,.. , « .. :., , . a r, F v : ...... ben:.,. _. . 150. (R, S)-4- [2-methyl-4- (3 ;-. methyl-piperidin-1-yl)-quinolin-7-yloxymethyl]- benzonitrile;

151.4- [4- (l, 4-dioxa--aza-spirb [4.5] dec-8-yl)-2-methyl-quinolin-7-yloxymethyl]- benzonitrile and 152. (R, S)-4- [4- (3-hycr. Qxyzzethyl-piperidin-. 1-yl)-2-methyl-quinolin-7-yloxymethyl]- benzonitrile. ... Examples of particulartpreferred compounds of formula (I) are . n,.. 2-methyl-4-pyrrolidin-yinolin-7-ol ;." ;. 7- (3-methoxy-benzyloxy)-2-imethyl-4-. pyrrolidin-l-yl-qumoHne ; ... . ;,,... :.. 2-(2-methyl-4-pyrrohdm-1-yl-quinolin-7-yloxymethyl)-benzonit rile ; netyi): be, n2onitrile; 4-(2-methyl-4-pyrrolidiiit l-yl'qúirlolin-7-yloxy. methyi)-benzjònitrile ; .'') "-. h'''rv 7- mesdiyl-4-pyrrolidin-l-yl-quinoline ; , 1",,....,. ~ 7- (4-chloro-benzyloxy)-2=riiethyl-4-pyrrolidin-1-yl-quinoline ; (S)-4- [4- (3-ethoxy-pyrrolidin, 1-yl)-2-methyl-quinolin-7-yloxymethyl]-benzonitrile ; 6-butyl-4-pyrrolidin-1-yl-quiuri-iolin-7-ol ; 4-(6-butyl-4-pyrrolidinJl-ypl, quinoliri-7-ylóxymrethy5)-behónitrile ;- 4-azepan-1-yl-2-methyI-07-1 (pf idin-4-ylmethoxy)-quinoline ;' , ,,,. 4- (4-azepan-1-yl-2-mehyl quriolii 7=yloxyinetTi'I'berizonx ; tiile",,, : a r,. -,, .......... '","r.''' 7- (2-chloro-pyridin-3-ylAoxy)-2-methyl-4-pyrrolidin-1-yl-quino line ; ylmeth' (S) 4-(3-ethoxy-pyrrolidg 7-(2-fluoro-pyridin-3-ylmethoxy3-2-methyl-quinoline ; (S) 7-(2-chloro-pyridinvoxyj-4- (3-ethoxy-pyrrolidin-1-yl)-2-methyl-quinoline ; (S)-7- (2-chloro-pyridiii~ dFy3töxy3 4-(2-inet4-pyrroidin-1-yl)-2-methyl- ..-f ..... quinoline ;

(S)-7-(2-fluoro-pyridin-3 ?-yimethoxy)-4-(2-methoxymethyl-pyrrolidin-1-yl)-2-methyl- mefh qumoline ; quinoline ; (S)- {1- [7- (2-ffuoro pyxidy 3aylmethoy)-2-rnethyl ; quinolin,, -yl]-pyrrolidin-2-yl}- methanol ; , :. (S)- {1- [7- (2-chloro-pyridm-3-ylmethoxy)-2-methyl-qumolin-4-yl]-pyrroli dm-2-yl}- methanol ; .-...... .,.,., ., 4-(6-iluoro-2-methyl-trolidin 1-yl-quinolin-7-yloxymethyl)-benzònitrile; 6-fluoro-7-(2-fluoro-pyridin-3-ylmethoxy)-2-methyl-4-pyrroli din-l-yl-quinoline; 7- ? hloro-pyridin-3-ylniZi : oxy)-6-fluoro-2-methyl 4-pyrrolidin l-yl-quinoline ; (S)-4- [4- (3-methoxy-pyriolidin-l-yl)-2-methyl-quinolin-7-yloxymethyl] -benzonitrile ; ''-''-''-''''''j' '. 'r ! T"i"' (S)-4- [6-fluoro-4- (2-hydroxymethyl-pyrrolidin-l-yl)-2-methyl-quinolin-7-yloxym ethyl]- benzonitrile ; benzonitrile ; (S)-4- [4- (3-hydroxy-pyrrolidm-l-yl)-2-methyl-qUiholin-7=ylbxym (R)-4- [4- (3-hydroxy-pyTrolidmjl-yl)-2-inethyl-guinolm-7-yloxymet r......,..-.,, (S)-4- [4- (2-hydroxymerolidin-1-yl)-2-methyl-quinolin-7-yloxymethyl]- benzonitrile and ?.... (R)-4- [4-(2-hydroxymethyl pyrrolidin-1-yl)-2-methyl-quinolin-7-yloxymethyl]- benzonitrile.- .,.... : , ; .,,, _,, ;. :.,. a-..,.. ; rs'r 1 SgrS ir-r. r. 4 r e r,, ~ Processes for the nia. a'cure of compounds, of fbrmuta r are an. object oftHe invention. invention.. The substituents and iddices used in the ibUowing description of the processes have the significance given above unless indicated to the contrary. ; y, . :. ,... Compounds of general formula I can be obtained according to scheme 1 from compounds of formula rising R2substituents according to the above definition by an alkylation reaction with, e. g. K2C03 as a base and in a suited solvent such as DMF. The alkylation reaction to intrbdn'ce R. can also beperEormed on the intermediates described below, prior to implementation of the substituents in 4-quinoline poition by inverting the reaction steps.

Scheme 1 ,;,,,-. R4,. Ra X R5 (4 :'vA. Jw. A I R ;.. §., A c,, R,, O v N R R 2 Rl-Hal R HO R3 N. R' .. p : : \-v. . ;, :' :.-, ,,.......... ''-) -''''''''""'j Alternatively, compounds of formula I can be obtained from Ib, according to scheme 2, by an alkylation reaction as above to give compounds of formula lc and subsequent Pd catalysed C/O, C/N or G/C'liinWbrming reactions in analogy to known procedures. Thus, substituted alkoxy, and'ammp groups can be introduced via a C/O, C/N bon'Sforming reaction under Buchwald conditions, from the corresponding alkohols and amines with, for example, Pd (OAc) as cayst.'BINAP (2, 2-bis (dipenylpnosphino)-l, l-binaphthyl) as chelating phosphine ligan<and. ith NaOtBu as a base-in a solv. ent such as toluene and at elevated temperature,. chwald in: J Am.'Chem. Soc.'1996, p. 10333 and Acc. Chem Res. 1998, p 805 for tlie general method). With repect to Pd catalysed C/C bond forming methods to'introduce the above'defined substituted alkyl and (hetero) aiyl groups : This can be achieved via Suzuki-type coupling g n e achieved via Suzuki-type'coupling, (for aryl, heteroaryl substitutents) starting from well described or commercial aryl or heteroaryl boronic acids with for example, Pd (PPh3) 4 as catalyst, Na2CO3 as base, in DMF . at elevated temperaturmethod : Synth. Commun. 1991, p5l3 An'alternative ,", consists in using the correp. onding aryl or heteroaryl stannanes in a Stille-type coupling (for general method Ang. Chem IE, 1986, 508). ,,.. ..... .......,, ... _.... Procedures to introduce''aryllcy, heteroarylalkyi consists of applying the reaction discussed above or to'usepd cataiysed C/C bond formation undér Negishi conditions, starting from the Imowh'arylalll, heterbarylalkyi Li or Mg salts, with Pd (PPh3) 4 as catalyst, in the presence of ZnCl2 and in THF as solvent (general method : Acc. Chem. Res. 1982, p340). Other methods (e. gifor arylethyl, heter, oarylethyl group introduction) consists . ; f : : of performing a Heck-e. coupling,, starting fro : m, a. corr-eponding (hetero) aryl. olefine and a's-base in DMF as ic, with Pd2 (dba) 3 as catalyst, P (t-Bu) 3 as phosphine ligand, < CsC03 as, base in DMF as

solvent at elevated temperature. (<3. C. Fu'in : I. Org. Chem. 1999, p. 10 for recent application ofthe reactiòiri). ; The (hetro) arylalkérie cHóndensãtion prodûcts can then be reducedfurtherbyhydrògén : åtion. i ; ; ; ''~ ; A method to introduce awgroups consists af reacting-ån alkine iwithw lc ; urider the Sonogashira conditions (review : Org : Prep. Proceed : Int. 1995, pl27) with Pd (PPh3) 4 as catalyst, in the presence : of CqI and with triethyl amine as a base. Alkenyl dervivatives are obtained from alkenes viå H¢ck coupling as pointed out'above, and alkyl as R2 substituent can be obtained from the. corresponding alkenes by hydrogenation. .. An alternative sequerice to perform above discussed Stille-, Negishi and Suzuki-type condensations consisits of performing an halogen/metal exchange reaction from Ic, to obtain the correpondixig ! stitines, ; Li ór Mg salts or bororiic wåcids. This is then followed by a Pd-catalysed condehs'atioh withappropriate halogenTde general methodsìgiven :. àbo R R "'. >NFJ', ;, ;".,.,,..,-< Ny Hal I l r » z ; > Rt i HO N-3 0 , N. A ..... : Hal . ..,, _. ... Nal R 1-Hat R p,.-.. _N, HO/.. a : N . R3-,. m..., :,.., .,. Ri I,.. Ib : °. : a, :. x : . r= .,, r,.,.--c : ,. , : ,,.,.... R2 ' . _ Rp... :. °°" ; , . _,,....,., f..., _I,.,.. !, <-. s,. A I 6'3 t X :,, e. r 3r 1, 7'; Z" i-.....".'1 1, ,. ; V % Lt. . ;.''., . /.. -, :,., 1,. alkoxyalkoxy, hydroyallcoalkyl, arylocy, arylamyo,. heteroarylamino, NI2-,

mono-or dialkylamino, heterocyclyl, arylalkylamino, heteroarylalkylamino, aryl, heteroaryl, arylalkoxy or heteroarylalkoxy. ..... Compounds of general formula I can also be prepared according to scheme 3 from compounds of formula II'withappropriate alkohols (RQH) in a Pd catalysed C/O bond forming reaction under Buchwald conditions as discussed above or by Ullman-type rection with, for example Cud, in a solventsuch as DMF, in analogy to a method described by J. A. Ragan: Synthesis 1998, pl599 : Schemes'- Scheme 3 R R' A Ru,-, ru-oh han ;, Compounds of general formula Ia, b and II can be prepared as follows: p 3 The preparation of compoún'ds according to formula Ial, wherein is not-NH2- alkylamino, dialkylamino or aloxy, is achieved is according to scheme 4, starting from appropriate anilines which'drue either known in the literature or which can being prepared by standard procedures ; oFn in the, art. tThus, condensation with. corresponding ,. N, .,. alkoxycarbonyl. ketones. or aldehydes in the presence'ofp-toluenesulfonic acid, in renuxing cyclohexane and under. càl4Xwåter produced during the rieáctioinithe enarrxine... derivatives of general forrEn\<u. la. Ì ; Vitareobtained.. Subisequent rirlg closure is achieyed on heating at 250 °C in a high boiling solventsuch as Dowtherm A to give compounds of general formula V. Transfqormation to the corresponding chloro quinoline derivatives of formula VI is performed on treatment with POC13 under reflux, a standard method known in the literature. Subsequ. eneation. with correspondrg.., arine. a defined above, either using a large excess of amine without solvent or on reaction with a 2-fold access, in a suited solvent such as emanoPor'THF and in the presence of catalytic amounts of NaI and with pyridine as a basegiVes compounds of formula VIli/The amines u are either substituted with R4, R5'gro'iips'as clefined or tlie groups cari be introduced by functional

group conversion as known in ; the art. P is a protecting group such as benzyl, ally or tert. butyl. Deprotection under standard conditions known in the art gives rise to lai. Compounds of formula lai can also be obtained from the corresponding methoxy derivatives (P=Me, formúla V). ons rnethyl ether cleavage with BBr3 in CHzCl2 as a solvent. Scheme 4 R ;.. ;. . p. 2 E'O ° pjo4NJsR I11 ....,' H, ;. R, ............. 9) I Recq Ros Rs. Y"1 s R O N R , t u..... R IV R P, 0 N R'P,, 0 N R3 v la, -\K, Q s mz < làa vil ;,.,.. R3 is hydrogen or alkyl ; P is a protecting group such as e. g. benzyl, allyl or tert. butyl; R'is methyl or ethyl.

m ul lano, dia*l Compounds of general formula Ibi andlli (R not NHz-,. alkylamino, dialkylamino or alkoxy) are prepared as described above from appropriately substituted anilines according to scheme 4 toscheme4. 2,, ak Compounds of formula iIå2, W h R3 équaling N^ tylamino, diallLylamino can be prepared from anilines of. formula III, by condensation, with alkyi cyanoacetates, ring closure and subsequent functional group. transfbrmations as described above. The ; . e I. x, : C ; yy,... t, : S : '. i.. l'.,', "'a. :'., i : _. t,.. a. t. :,..... : G4 : '' correspondihs'compounds with alkylamiho or dialkylamino as R substitutents can be. m., r. . .- ;,..,.., ;. obtained from, for example, intermediate IX or yil2 (R, = NHz) by selective N-alkylation. In analogy to the sequen2e ! deseribEd in scheme 5 and sharting from thié~appropriate. anilines there can be obtained the compounds'offbmulalbz and Hz (R equaling, NH2- or aLkylamino or dialkylåmiiiio).'. allcylamino or dialkylammo)'. ; heme--5.. , *,, c 2<. i. I. 2 . s H.., ! s. :. _., v'. f. ; ,... ?.. _ d$.. ^. ^ ;, _,. .. r rs... te : . L. ; :, t.. : ?, r,,,. .., , : ttJ'k :. L :. tG.. : ; ;. : ! L'.. tt R F, 2'=t' Ir _..., i, (.. r. i ;,. ; wti. . . r,. cfla°.. < t.. r, txr p'.,", . ,. ir _, .'te. _..,.. n, ,, a.. _ ;. 1 Z g n n N" p 4. erz I... 2 w Oil '. ! I -. F l."",, . .. a. : n ° ..,. II ; I.. __.... ve'-, 3i'1',.'v. t14'1 i ? ii9r e"lS 7L T,"47,-., Pt a"t. f nu -.. t'5 ;" :, ', '" °'., i,., t Sv .. f_f_ ;, R2 RisNHz-, alkylammoordialkylaminp ; R3 is NH2-, allcylamino or diallcylamino, , ... R'is methyl or ethyl ; P aprotectinggroupsuchbenzvl. allylortert.-butyl.,

A further method to prepare compounds of general tormuia Ia2, Ib and IIi comprises condensation of anilines of formula III with malonic esters to give compounds of formula X. Subsequent ring closure provides the 2, 4-dihydroxyquinolines of general formula XI. r,,,, Subsequent chlorination with COCI3-gives then. the 2, 4-dichloro- quinolines of formula XII which can be selectively transformed to compounds of type VIIZ by sequential substitution reactions with the corresponding amines-in analogy to Ixnpwn reactions in the literature. By this. prpcedure there can also. be obtained compound. of formula VIIz (R .."..,.. : : . :. is alkoxy) via sequential treatment of XII, with correponding amines and alkohols. The 4round compounds Ib25 II2 can. be prepared in analogy acc. ording. to scheme 6. : , . ; . .. .'i f '., ., ., Preferred > T r rP l t, ; f, ; ; E 7 ; L e , ..,.,.". t...,,.,. :,.,,. . i.-,". : , Scheme 6. f °. r ;,. : : 1 I. :. : t_ tr ? : '. 7 r i ; ! 't, t..,, t. , x... '_. i y ppic ac (' R2 \ 'R ,./, ,, :.. 4,,. R..'.. " P}.,'",, ; i S} t<O, H R'is met yl or"ethyl>"fL 6 i t ; » r'K i"St-^ P., , O N OH "2"'---P --'P ' .. S., , ,.. A n.. v,,..,.. ,., rEe,. 1'.,..... i . 1. . : x ..' ..". , ; II r.. : 1 ;''s. j.,', s. , . . T., :,... u : ; yt, r : ".'.. 'i... d 1 _. 4"t, i. 3 a : s. e. :' ;'." ; t. x.., _ i, s,. R"ismethyldrethyl.'°'."'''''.'. ;". " ; -''''.".'r"'""''"''.' ;-'.'''7''"''"'"''"""'""--"" ,, u,,..,, . ... 't 'z,.... can be carried out by. trinentosuch i'n'organic aGid/frample a -" ,. :,. I. .. ..... R3 is NH2 _..'alk'lamxo,,. dia. lkl amyotox alkoxy,." i J, r. . I IU w Z is tmethyl: or ethyl = Th, e conversion of a coinpound: of, forniula I: iito: a-pha. rmaceutically'acceptable salt can be carried out b treatr. ne. nt f siich a cbrni: ound... witli, an iiior anic acid'fpr e'ain-le a h drohalic acicl, °such as, for ame h drochloxlc. acW: or li'drobroinic acid; sulfurc..; acid, nitric acid, phosphoric'. abidr, etc, j or wifh

acid, citric acid, maleicacid,'& toluenesulfonic acid. The. corresponding. carbpxylate salts can also be prepared from the 10 The conversion of compounds of formula I intppharmaceutically usable ; esters or present in ,, ir'c i . ,.,,. The conversion of compounds of ormula I into pharm, aceutically usable esters or amides can be. carried out;. e g ly treatment, of smted amino or, hydroxy. l groups pre. sent in, the molecules with an. carboxylicacid such. as acetic acid, with a condensating reagent such as benzotriazol-l-ylo t) Ph°sPhwihexatluöro. phosphate (3O, P) or- N,N-dicyIohexylcarbodumid'e ; (pCGI) to'produce A preferred process tor the preparafion bf a compound of formula I com ., prises one of the following reactioris :" -' , l'vY. ,, . 7W. «, .. : p LL.' :.'. r". x ; (l. i. . ; : e. , ; . ; r a :.'.. ni.., :. L c. u. I. a- > :.. r. : ' ;,, a reaction of a : o ond o the formula, Ia m,. 4. he xesence-of a comounsi of th'. .,", : ca. ^ :-'. 5, : ., o C'E".. _.. r.... : t.. ' tt.-.. s : i c,. sbi3 ;'., P.. "w 3_<'_. , : 2'"41.. i. i. ;. r. y). a. . r.,-. R v.. t. 2. . v, r v... i r. K>. . C^ r4 wf. l, f'1 S. J.. r.. 1f .. n.- T'eliv t. nF.. rvW. ... .,.. .. ,',.... _,.. V.. , ,,,, w. herei'. nvi, R, l +dt3re an. d. S"o"gren ; ; or ho nu ; . rr wt, R s u. f. 6 I. vS. r r^, f u. _t..,,'g. 1 R : ', E. .. 1 ; v',' ,.'.". ; y"', fr V'R', ; , ., , ti 1 r,. tt. ;. (, <. .. , R5 f., :, ; °. i., : :. i7. ; T' : ....., ;., v s, .. _ ?.. \ Sn. cr.. Gc., v, ; ' , ! '". t,'-^. 4"t, Y,, 'T °. _,, ., 7, o _L'c,., b-, i , t.. . . M, i..., c. uI ; .., q ° E w.. t Y L. v T 4a," wheei: n. Rl 12 R3,, R4 R5 and A are as deed:. b., e'ore and Hal s. aloY en. or. b) Pd catalyzed C/O, C/N oi :'C/Gtiond forinmg ieaction of a coiiipound of forrriula Ic in E i uk Y t Yt'!}-lUtS R4 ai ; i r i' l ; / u :..- a Aiar X, >"e,"2, >., n, ;"dj ìs, L,., oo ën>4 H I R 2 ...,., ,.,.''I :-..,,.,, :, : k,. : ., , j .,,., f, 1 ?, ... r a.. ;.. s., S,,,."i s... ... 1 ',..., s t .. ? _ c r", RFtS,-. oa, r.'> 1., : t [ R4 s. a.. . , ;'' : A.. :..., t..,. A. ° R.. _, '° L''.', ...,, hial y 7 \ R2'4, l 'yZ. i t .. 1 ee ° y >,' i t_ r r tr"tf wherey I2, R., R, R.,, R, aiyd Aare defined as beore and'=Ial xs=halo eii2 preferabl chloro, bromo or iodo_ Preferrediis the xeaction of a, compound accorcling'to

formula Ic under Buchwald conditions (S. L. Buchwald in : J Am. Chem. Soc. 1996, p. 10333 and Acc. Chem. Res : 1998, p. 80vi for the, general method), particularly in the presence oPcl (O'Ac,) z, BIN1, P'aid. a. lias su'Gli as'NaOtBuvifh -corspondingr alkoh61-bramine'. inQrdr% o fct d-'6imula, I,,. wheiein k2 : means. MI. .,. t,, ,,, :, ;.,...,... '.. r : t '.,.. :''. ° :. ; _., und. er Suzuki-tye. couplmg condWons,. (general method Synth. Commun 1991, p , w, , : ; t, y ("i.. :'7' ! .''' _4ry.,,. gTonic, aci s or e eroarvidoro, nic aci s in order to'rm acomp'o'und qfform aryl or heterbaryl. Also referred is the reaipn'Qfia compound of &rm Ic under Stille coupling. conditions. (fr, gTju,, n-Che 8-). in' corresponding arylstannanes or. heteroa"iylstannanes m order to form_ a compound ; :, ; :,,... stann ; inesi) i. etero tannanes, in, or Pro., cWe, e, d ; : Ir,, ítX r ; tiln6thetp"enc$ u9Lnu e,"sKu,, a, s triehyljamin&inthegEes. eN ... : , p, ) : ,",,.. ;, '.. > :.. : z ?.. : a. ,, x, ..... .. :. , .. 4.. : . L : A, r> :... x.... _ c) ahalogen/metal' ! ecMnge'neae an. d, sub+4 +++fotWW oFfar. mula, Z,; herein RZrm, eans lkyryl: ar, ... L; <, e,,.,,; , t.,. ; ,. j;:. c a halo'eri irietal echan e'reae r'o; zi'tiacam onti:. o £biula Ic as'cie'-ned. iri" sfie""'b and subse uent P eatal.'°'Ed d'i. ensation it'alialo e ide r f the fmul: tR2= al to yielcla cciipouxfd o'ormiaVT, w'hemn Rl= ; kR3,'R, R"aid Aarefs. clrfined'as °y :.. before, Hal isS sS idiA B. enY ryäog ; iirLyloiF,,. arylamiii'o, htetér'obàd I2iiri mbri5 Vatc> díaliçylárninb, åiSyle ; ylamino, helSéroärylBylaniitno Xig eter ? b9jry} ór <ti tot ci.'t's. ti> ,.,.., ;, T, t A,, : , . ;, ; 'r : J 'i 1 6. i, . ; N t : ; : J. p k fi,'_.)",,, : r s, ., ; ta h, f., d) reaction of a compoundof formula II'in the preseiic of'an llcohol oft. he formula' aryliiici li (t,-e, r"o, 'a diiii6. : arylaklamino, . ; 2,., t", \ W e,",,", ,, ; j, tr 7 i i ? -ru , r3+ e Si w. lj. ; w ! tI't e7, h tC) Ç Ati"r'''i b fA,.. ? ! , F hett64iryl. a, rii r ''-''..', '-''-' ;''. '. (-. . T,- '. i ;''.'tUM. E-'r'-' ;."". '\-'-' : 7' ;'-. ' R s . Rs '''" ' ;''. t, a'i ,.-S-^ y,. i ?. a 7't i k E . 5, l. _... j . 7 M 3 i. tf , f-1 i Q a ir , B, , r..., . r, i u ; i wherein R., R, R, R and: A are dened as before, Halys halogenYand Rl is hyarogen, e _'; e . 3': y 1 t r i1 , i-; W aIkyla alkoxYakYIcakeriyl ;'akyyl, hvdroxjTalk'pl,'arkyl, heteiocclylalkyl," °-° : ;' d*cloçky !'atlwi<Sw 2- zut Y :,, Y. ',. z. , ,, '"-.,.. 2,. x. ; ', , aY..... : a _,.. r,, :. ra..,.. _.,. :, ; t.., , : : :.,. c_ : :. i .

-o""l'"'aox"y'c'arbo'n"yla'llrl"- carbo T'a 1 SO O alk3Tl.''c clo; 1 or co 1 1'"'' x3'Y. . ry, a t, Y, ' Y , Y . . , : °' w., i : _. : a : : s', : ,,. _. c" ; ; r : i <. c..'. !'. :' ; A particularly preferredproceSsfor'the preparation of a cbmpouhdb comprises one of the reacfions x), c) or d) as mentioned : lefore : ' ;.. ;, ;.,,. I f, b t ;,'. Preferred intermedi : ates are ; , ; 7-benzyloxy-4-chloro-2 triethyl-quinoline, 7-benzyloxy-'6-butyl-4=chloro-quinoline hycirocliloride ; ive ; ... , a : P t , . .. i r ' !''. f ! :''i,,. 7.. ? tdi.'N : a ut ; r,. y. ; . tt,, !. :"_t. _. _ j . ' : W. r. t'.. c' : : 54''li tkF-,. °, :. j 6-bromo-4-chloro-7 met. oxy 2-methy, l. qumoline. . The compounds of foxzla T described above-foriuse as tliexapeuticall actv... ; i i i, i, j ¢ l E I ; S 3 ; f t t 71,. <i,,'l. ; >, i j « 4-L ? 6.} 6 f f i ; 7';.'!, i f g ;. ! ; 3 ; :. ; i ;, I c, i. 6 &í ; 7 : i i i f j f, 5 í fi ,' !'-"" ! : ! :.. ;-p ?'' ? ; . ! M- substances are a further. oect. othe ; invertion...., : :. :.., ,. r. _.- :..... v. ,..., , .... , t, y" ,... ° ili : :. F. . _2', :. ; : ! 7-. .,. 1-LF. f _.-r_''.', y.. _ : tjv.. _. x', : _, t, :,..,.,.-,.. Also an object'of. h'e: nnveritioiiare coxnpourids. descrnedabbve'for fhe production of medicaments for the prophylaxis and therapyof illnesses Which are caused by disorders associated th, the NgX7re, tz çpàrticularly fè'r the'production of medicaments for the prophylaxis and therapy of arthritrs, cardibvascular diseases ; diabetes, renal failure and paxticularlyeating. diorders an, d : obesty-. ;, ''-''"' ,.,. ; . I ; ikewise-ar. obJect ; of the. ixa ; yntip are ; a-macmeutical compositions containing a com ourd. o. £forinula I described abo ; ve and theia eutcall inert'., c'arr, e :'r : Ánobjë ; tfie. v ;'b i''e<. e, ds, ab309 é ; fö, rthe *'"""' !"'"t' th-"h"I production'M-, 4", f, 8-of diihii-tis, An ob'ect of the invention, is also the ue of. he com p ouds descibed tabQve for the :, r.."'.'. t- s. 7". ta, "_. i-. :. tY, : ,., sd ; ;. H. x. T, i ;,. .'i .. . 5°. :. 1 ; . ^, r E, : jtw ! a'.. ;'Y i e<. :. :"' ;. ? !,.. .,'... the . : t S l ' ;.-,., x.. , P p. Y. cardiovasctilar diseaes; el. iabete; ieW 1'failureaniiparticuTarly, eatiiig clisorciers and A further objectpf the : invention comprises compounds which are : manufactured .,.". : r ;.. : ;... i :. # » y-s. ; :, ? ?" ! . 4_' !..'t.... c §cv ; , , , , t.-x" : J. : t.. ti ; i :..,. 1 : : r, . :.. . a, : : i. if. : F..., accordingtsoonneF2ftßdeswr+s tutalSsS JAi..'.' ?-7wv5' A mrtheobjecofiny the. treatment. and prophylaxis of l., ..,,.,...,. :.,., : : P :. rY,.. . F,- arthritis, c. ardiovascular dis ases, diabetes, renl-failure and nraticularl)', eatin_T. disorder_s and obesity erebyjanGtive a aboye. is administered. Accordingtçi ? tz+ ; <t, i ;,-1ts, tX ....., . r" : 6 :',. Accord.'inq to furth.'er as'ect ofhe i ventori ther, e is ro. vided : a_, 'method of ... 27. d u. it f i qi. rC.. y i, 1.. E.. F ! ^J 'w 5,. 2, 1'T _-. ; irs. treatment of.. obesity, n a htman y reedr of such'treatmeiit w, hich coixiirises:

administration to thhumanatherapeutic w*V 7 t''J"is 1., J'. to formula I and a therapeuticaUyeffecdveamountofalipasem preferred, wherein the lipase inhibitor is'orlistat.'Also subjectof the present invention is j ect, of the present invention is the mentioned method, wherein the administration is simultaneous, separate or ... _..,, Y.. A further preferred embodiment of the present t . 'i :',. !"".. of the formula I in the manufacture of a medicament for the treatment and prevention of obesity in a patient whqis also receiving treatment with a lipase inhibitor, particularly preferred, wherein lpaseyhibitor. is orlistat,,., hob ., Assa- oning, NPY-5 iecept thé . : r-. a.,.... ,.. r F- a'"', x£ t"t, . L' u, :,,"C f.. : v... 3.'. ? f', ? C :. : i4 7 t. d3^r... t : £ ;. J7, =r t'". n e, pu, ,, Assay Procedures,, ..,.,,.. _, CTbniri f iriouse PY5 recetor c'DNIs:. ° . The fLdl4ength-eSencciding, thempu$e Gept. pRwasampliied from mouse brain cDNUMgsppcicprimere sequence, and Pfu DNA- ; qlvmejEase, (Stratagene). TheiamplinGation-productwas,-- 4en, ceci ari. 4, one. C11. subcloned into the rilammalian, xpressio. vetor pcDNA3 using Eco RI and XhoI... restriction sites. Positive cipnes were sequenced and one done, encoding the published sequence was selected for generation of stable cell clones...,.....'''' Human embryonic-, e 10 ttg, MNPY5 , . i, l I ...-,, :,,,',.. 5 d T ix"^t dia sin w i'''"Stable transfeetion Human embyonc'kiiney:: ... (. TK2'. cell'sr. W. ee_tr, ansfECted vzth 10. tg iiNPYS DNA using tlie lipofectamine reagent (G2ibco BRL) according to the riiariufacturer's .,.... c.. c :, f _. r, ly.,'-rk. l.. j ;'.' ? x. :'.. ' ; ,, : s >. o.. £. :,. tY. :, ; 5 ;."n> ; , : r,, ; 7t'.,,. : instruction. Two days after transfectioh, geneticin'selection. (lmg/ml) was initiated and ..,, yF t, c-, wa ( a-i-. :, ^ _' ! y, ; : y'x ;,' v6 ; K, d -I4 a ",, pTn. h73'a., several stable clones were isolated. One clone was further used for pharmacological characterization. . n w ;....,. mye , w. Radiolyarid coiiyetihon bWdmg_.,,, = t..,,... il c 3 1 ressi g-,, reco m nant,, mouse NPY5-ie ICe'pff NPY5-recepforP (mP).'ere, broke

buffer (5 mM, pH 7.4,1'M-K, MgC'2), homogenized and centrifuged at 72, OOQ x g for 15 .. : : min. The pellet was washed. twice with 75 mM Tris buffer, pH 7. 4, containing 25 mM MgCl2 and 250 mM''sucrose,-. O'. l-. mM'phenyImethylsulfbhylSuoride''and 0. 1' mM' : l, 10- pheneanthrolin, re$uspeieled m-the sarrie biffex'arid storeda m allqii. ots at -80°C. Protein was determined'according to'the method of lLowTyPUsihg bovine'serum albumineBSA) as a ru-biiiiii ! (BSA) as a standar an Fyi d i'"2'5'9," ; 25'inM'lepes '1 54. r'.. 1.,'.. i . i. n ..-.... . , q .,..,. ...., , '..... 1..' :... ^.. ...,... I Radioligand competitxon ; bn. ding assays were performed5 m'250 1. ; 25 mM Hepes buffer (pH 7. 4, 2. 5 mM CaGlz, 1 mM MgC]. 2, 1'% bovine"serum albumihe, and'0. 01 % .''',..,-,.'.''125.'"''".'..'...-.''.. ". 2. ^, r. e :.'-'-ai_ ;''j). : t-. ; ;... ..'.,, -a ..),..". : ". .. m _ ?) t ky" containing increasing amounts of unlabelled test compounds. After incubation for 1 h at 'n'defi'd-' binding is assessed inathe pxesence of 1 >M unlabelled P... Specific, bmdmg lS defined as binding is assessed in: the:. pres. ence o£ 1 iMlunlabelleci PYY.. Sp, ecific, binding is defined as the dlfference between totallbming and. non, speclac binding. IC values are defined as i ^- i f-d thé,,..a s 2 r s 2 i i sa SjL g 4 ; ^ ; 4it 5 : w, ; g, I ?,. : :.. neuropeptide t is 'tdete'r'M'ined'-'by,-Iln"e"ar'',"r'egre'sslion-analysis a er ogit/log :.-.., >" Z". : _ transfoimation. of the biridmg data'.,-'.' ,.... t ! t. k, " ., .., , ... Results-obtained C : e fk-gói'ng tést.. asì-4 T, epr-ementatiite^ : coAt ; Of otlie inventiori-as the te'st copourids ar. eslion°. iii thefolloivirig'tali'Te. _-°"F.. : f. za ; ....' : ... 7cy-lopr6py-ieffi6x .. l. . L. ., "Y -pyr -quinolirie. : (, eihiple--', 5, -1. 6-biityl-'-4-I ; y-'irlidih- 9 quin Xquinotine (¢e {amp, l, e t ;,,".,, «,,,", x 6butylXo ? q Si : çti jRi ? ; ;-''ki'6 ,, ,-z -TSOnM) a f c , i. ; s, ,. '-''qumolin-7. bli- (emmple'34c-nu."'''i''''.'.'. i-,. : r''.'' . methyl-4 pyriolr. dm': 1 Yl. : s ,', Y . 7 > :... _. i qmnoiirie (exarnpl, e 5z) '-,,.

Preferred compounds described-above have IGso values below 10. 00 nM, more preferred compounds haveICso values below 100 nM, particularly below 10 nM. Most preferred compounds have, ICSO values. below 2 nM. These results have been obtained by using the foregoing tes, t- The compounds of formula I and their pharmaceutically usable salts and esters can be used as medicaments (e. g. in the form of pharmaceutical preparations). The pharmaceutical preparations can be. administered internally, such as orally (e. g. in the form of tablets, coated tablets,, dragees,. hard and soft : gelatin. capsules, solutions, emulsions or suspensions), nasally (e. g. in the form of nasal sprays) br. rectally (e. g. in the form ; of suppositories).. However ; ; the administration, ; ca : n also bb effected parentally, such as intramuscularly or intravenously (e g : in the form bf injection solutions,. ?";./. i T), a,. 2 7, 04, ; t. Fs,'t,. ss ; ; % (H 7. r 7 x. re ThecorpouRdsbfrmula'1'and be processd-, Mtlfphar. dd'ci-ii"tic4, be processd W i'prriiaeuticallyimer-yorgaric or''ogariic='clju. vaits=or the= production of 1 ; ablgtS)'coated'tablets, dragees and hard gelatin capsules. Lactose, corn starch or derivatives thereof, talc, stearic acid or its salts etc. can be used, for example, as : : yyrtr. : , t. pa' n. , i. ! :. i' : : r34 v. _32,.. a n. l,,. c... i ;,. m, .. . LIL.. wr :. k. ;... . .. ? 1 such adjuvants for tablets, dragees and hard gelatin capsules. Suitable'adjuvants'foBSofEgelatin'G . for e Suitable adjuarits, for soft : gelairicapsules,. are,. for : eXariiple, : vegetableols ; . W aes ; fats, semi-solidsubst-ånters ; ah ; d fid : pç ölsXetcv>. ? s, f., s, tl~~S ; t, water, p, olyo. lss. sa, c.. char, oie. <ert. $ugjar, ;, ¢sj+ç<, e, tc ; j"; iFie-rt ; ; ;. a Su, itable, ata,, r, lXrl m, geFEu% +, o, ns, áSre, a,, « l. e5 ; 7 ;., wL, a, tter NCo"kHs ; P°lYrD] s7 glycerol, ve, g, et, iblMe it. s, C. ; ; 7 i ';. ? ; > ; ; X ; : <''''; ; trj-i"C < water,. poxol, s,, accharose, mvert ugar, gluco, se, etc Suitable adjuvantsorthepr . J..,,. £.)., n ; 'Z n p.,,,, al, ohols, polyol, s, Suitahl&adjuvantsr glycerol, vegetalle. als, etc. , ,.. ' ! 4lizu :... . fa. ., c'. . t1_ ^. , ri.. s u. _>i ;" (. x. . l : d. fi rwy.,. k,.. ef. t7e s. k t-.-s., waxes, fats,, semi-sqlidoliquitl. polyis, etc.. .' ;..'. /.. J... ., \/ ; i'. .. t. ,...,.- ". .. '.', Suitable adJuvant"s for suppositomes aie; for eampTe, nafural or hardened os, waxes, fats, semi C olid oz liquidpo'lyola etc. °, °' r;. Moreover, the pharmaceutical preparations can contain preservatives, solubilizers, ,,.... j 7-xs, tj , ,),, t. < ;, e. ;,,,"ey z :., I..,. ; C. '°', .,. viscosity-increasing substances, stabilizers, wetting agents, emulsifiers, sweeteners, colorants, flavorarits, salfs'foi varyyg the osmotic pressure, buffers, masking agents or antioxid"ants 9e Wr it+HÙ ? sE, antioxidants. They can alo contain-still other therapeuticaU . ' ;. z, a u ? L,,) f Fs. 1 r. _ bal ° ; ) n 7 r'S Y 4, tt1 °. X. i : In accoidanewifi fiheainvenfun: lieAcoin oi; inds; offormula I and their,:.-v pharmac, çutica, ll, y ustMse, d% g t, zh. e tat harmaceuticall. us be yalts cai b used for_the, 77y. r. o7K-h'T, laxis arid txeatmeTtt : o. arthritis .,. . r^. vY-r,. ,, _' is., x .-k,., ja rl : ".'ria-' : l^1x. .'."L' ,-it. 'y. u&. t. 3 r :"d c. C :, ;, d ! itl ; ; :. f-..--y.. F,. ,... tn. "\ : :'' : . :'' ! ;. . cardiovascular. diseas. es, dJLabetes, renal failure'and particularly eating disorders and

obesity. The dosage cah'vaTyin'widelimitsad'/bf course ;'be fitted to the individual requirements in eac. jpaiticula'case/ In gene dosage of about O. i ; W » 2 » A+d8WeiAt, prefetibiy aboút'6. 54rnSg"t'ö'Xper kg body weight (eg. aboif 300'mgper=ersori),"dW icled no pieferably'1 3 iidW dua : l ,. , . ,. doses, zvhicli cari consist ; =oreample ;'of thesarrie'amounts, s. iou. d'be a rti raate : °' It vill, e. .,." ; however ; be'clear thiat he'ippelimit gmen above can e exceded vien this is shown to bye indri ...., ,..'d.,..,. ..., s.,. . r.. ..,.,,,' ! °, i s., -.. r." The invention u. illustrated, hereinafter by : EXarnples,. which liave no Iiinnrig ; " character.

Examples FJ t r Example 1 a) A mixture of 534 mg l.'S mmol)'bf7-benzylbxy-4-cn 3.77 mI (45mmoI) pyrroIidine''wasKe ethyl quin n6 atxizos herefor 23fi after''whiclitminetlie reacfon'vvas coinletecl accordW' :''tor-IPLC P., r,... ..,. _ P.... g..,... analysis. The reactioi waspartitioneii'bete"en ; EtOAc'arid water, theaqueousklayerwas extracted'once vith-EtOAc, he combine'cl organxcrlayers yveryvashed : witlivvatei then' saturated NaCI'solution,, ; clried o. yei' rriagnesii. irn sul, phate''and concentrated.'in vacuo. The go,.,. c o umn. 0 eluent. Combination of the purified fractions and cdncentration'-ih : vacub. fgave 430 mg (74.5%) of the'7-berizylõxy-2--mediyl-4-pyrroli'diri-l-yl-qúinolme ås'a'bro'vtn solid.'ISP mass spectrurii, 3 l9 Preparation'o'f"ih-'ta ,, ; i t -i ' ;. y .,,,. b) 20 g (98. 4 mmol) of3,-benoxanili b) 20 (. 98.. 4 rnmQl'o, ,-b, en,, o., anline, 12 6 rrl-. (0 984 rnmol\\J of eth1 acetoacetate and .., 'J7 ? . k Rt.. : JL.". :. t. ! < b. ; ;. r ; tt. . xi , r. cw. °, : ! f c. . ; . .. : '. i.. y7... e :.. _ : L, -posy was cooledtov, s, o km, et, sjolidi >, m,, atef vas, d Sffib » sucltivr,. thelfi, l, tratje was.. heated at reff fo. r, 5 5 h i ; the. : nxesetce of, a ; vater.- e azator funnel'le, reaction.. miture vliLi S.'. y ; . , ; W, r. L Cf,, t ri "1" a, °1, 7I. Cpzrs,,,. _'', 1., _, xi !., k.,., ; 5, the next reaction stepe 7 i-'< 7-'f ! ''r (d Z concentrated in vacuo td: me 3Q 6 9 °lo of the clesir. ed: 3 3 b. en lo. hen l i. no- but-2-enoic acid. efihyl estex as a; yellow.. oI; Ths was usedwithot further; qurification_in c) 3. 67 g (11. 8 rnmol) of 3-(3, 1-benzyloxy, phenylamino)-but-2-enoic acid ethyl estér were ,. _7 dl--. ; 7 F. " ! 1 . 1" added diopvise withW 20 minutes'to'-5 5 nil of Dovwtheriii A heated-at 250°G' (iriealbafih j, p ''"#'a.. r. >. a.", : .,. Y-. t : 4, %, w . : ,. :.'..,'",. i. :' temperatü) ; Thiè'; s sd fufiher A riiltntúté5oóG (báüiEtërare), ...e; : _ ;- temperature), the sblution! cooled tP RT and theh'treafedWi bu thatnad'. , . t n i r a,. formed was isolated an'triTatedth'5' bfAc'OEt :''TliebroWn solid bbined was , filtered off b suction, washe AcOEt nd driea tn a'high vacuurri fo gW e T: l9g (35%) of 7-benzyloy='2-inethyl''qumoin 4-01: ISP mass specruiri; ifie =6: (IvI-1 - (35%) of 7-bentio -mëWióu'@ec ; X>m, ; kSë.''2'ó6''3 ca ,. oxy calculated fof C'H-l'-' : :'26, 6),-,. ..'', ,,...,".,..'. : n :,.,., S, ; ; p ',. .., 1 !' :, d) 1.15 g (3.9. 9 rizniol) of : Z bezizyoy-2 nnetl'1, uinohn-, ; 4, ol. yt, 7'46 ; zl (79 : : & mol), gf ;,.. I , a. 6...... POC13 were heated at : 13. 0°C ; (bH bali temperature) for. lh40 ; m.]. n, until completion of the

reaction according to TLCnalysis. The reaction mixture was cooled to RT and the solvent was removed in vacuo. The residue. was taken up in ice \yater and stirred. for 2, h-The ! pH wasadjustedovalues : between'. pH-p, withJE precipitated was filtered qN', bysuctiqh, ; washed-with water and subsequently dried, in a high vacuum. This gaye. JLg, (84, 5%) of7-benzytoxy-4-chlqrp-2- : methyl-quinQline as a brown npln as a brown solid. EI mass spectrum, m/. e : 283'1 (M+1 calculated for C17HllINg : 283) ,,, . ', + Exampi'eS,'",', :,-++.,'<..-.,,, X, f _xainle. 2 :,. ° Asolutionofl3gof7-benzylc-2-ipethyl-4-p example 1, dissolved in'ySOmltOfMeOH was treated with 4 2 ofpalladium-on charcoal . 7/ . e7i' ?..'.'... Z. S_fr 8 a ; CVtf .. t, 'ii, 1 :., f... a. : » » ;, , ft'-r.''. °i°, °' ; x 'v. ( :'-ri . ; e, -.., , , f,-.. is'S : ; tj'f'_T'. 1. (10%) and then hydrogenated at RT for 1. 5 h until HPLC analysis indicated the :. i'. : , , - : _ : i. Je.. =1. ' , . .','lv. A. a : . adn t, : . .. d' a. 2y = r yt7 ;., s. i rry. _t, : . : :- kx, i ; . r. completion of the reaction. The catalyst was filtered on'washed with water, and the . yr^ :, z,.., 2. : : i . : M'a, r. , , : ;.. ; , i°, .. G" : "" t'. _.. i'. I..,. ;, :. c . ; < a, Z. . i'. ; rr", G ; i' ; ',. :", solution was concentrated in vacuo. The solid that precipitated was collected by nitration . : ; t :",...., A,. d=.. f... .' :'j' 'i,., r'.. d, n 35 ;, y°.. , ? ,.,. _"^''a'f-. lsJ..'.. t'r. ! . : :' : .. e. : %'. a. Y., :,. C. _'- : :,... and dried, in a high, vacuum to. give $. 9rg., (, 96. 2%) of 2 methyl--7yrrolidm-1-yl cuinolin- , _,, 51 S i,., 7, ;,"' ;,,""6" ,, v, ,, f... F . ' ;., zt -, _ T', < : ° : .......,.,-.. - ; : ss. <ir. L. ' ; :'-d. . r-"-'-c... , _...,... ; ^.. : t . t' d. y ., t E Ci4HisNaO : 229) : x.... °. u., , completion of the reaction., The catalyst was. filtered-with water, and, t solution was concentrated-in vacuo. The solid thatprecipitated, was collected by filtration moleculaTsieves'. (4nm) : ; were added ! followed'. by : l m'g Clmna : olj)'"oB pstassium fert-., , e, : 1, 5 J'_ (.,'w 1 1-'., 4. 1 _J. 1^.."4_I ; tYI, t j st. 7. ? gr'2,, .,. f... Aa, i J,. N., L, ; ,..,. 6 r, 4" ; ..''. butoxideand'themixtureiwastiBred'. fbpl .... , ' : wr'.. u,.- :''l, ys.'iW x., {,., y... , : ?," ;- :.. j" : . :-. % r r.. w. _t , _ °^'z. . k_'<t.. .. . y F' I. O. I3ml (l : 2mmolN', N-dimethyIsuIfamoyIMbr w t vi fi t 1','f !. t ;, s. i r,. 5 i, ; S La i"-. L.. \ 5, L, v ; 5 S ei i i e ; reaction mixturewaspsrtitionedvbetWeen'EtOAc'ahdwaterme a'queoulayer'w' .,..,. . _t. ! v ,.., r, ^,. : _,. ! n. 5., .. t, s. .... i !, 1,", extracted twice with'EtGtthe ; combmed orgamc'layeES'Wwashed-'with wa ni, c ayers with saturated NaCl solùtion', dried'óvermagriesium sulpWate änd c'orícentraed in vacuo. The residue was triturated with diethyl ether ; the viscous oil bbtained was filtered oEf by suction and dried. in a high, yacuum : Upon further triturating with heptane solid/material was obtained which wàs, drìed. in'a h, igh O give : l,. O,, O mg (29.. 3%) of dlmethyl- sulfamic. ac. mthylr . a,, : . ; Y. . ,.. ; °'., t » r. Y . 5 : y. 1w _euGsi,... w, \F.. : j. Y ! fX. : : : 1'p'w. try"... li, . u ....... mass ectrumm336 mass spectrUm,, l <6 aaNIellf9r c, S6 65 ? e

Example 4 ff + In analogy to example 3,'from 2=inefhyl- pyriolidin-1-yT-quiiioliri-7=ol, product of example 2/ahdmethanesulfbnyl chloride there w met'h'anesul6 :) hic-acid 2' methyl-4-pyrr61idin-yISqumoIin-7-yl. e m/e : 307. 3 (NI+l : c'ålcúlåted FriQ5PfjgSP f, > +."--". i, 4., 7,, ; i 1,,"t'. , s S r,.. '''''".'''"'Example 5'' In analogy to example'3, froin Z=niethyl-4-pyrrolidin-'l-yl-quinolin-7-ol, product of example 2, and cycloprbpylmethyl bromide-with reaction times of 19 h (0°C) and' isolation of the product as hydrochloride, via treat'merit of the reaction product with HCl- saturated diethyl ether tlere Was obtaind 7, =yclopropylmethoxy-2-methyl-4-pyrrolidin- lc'.'S r e., rof, t>St t ; t f.', i.. et'. r ili ;.'...'d ; y. '".'-''T :. : !'-tf/. r :-'' :'r ;. ?''''t'dibrlt'he calculated four , ,.,-. '1, f1.'i : _ bu r, t. la.. f","rl -C ; -b.,.,,'x.. 4, 9. i"a, a. 53is. . :.. r.' : .. t,.. § : ? ;. . .. . ii, A mixture of 114 mg (05 mmol) bf2-methyl-4.-pyrrolidin-l-yl-quinolm-7-61, product of example and-84 gl (O . 6 mrnoj,) opxf- methoxyben chl ri or23h. Thernixture"wass ; lcpoledhoSTiimdp9 orxjeLdbfie, WeeS, caMRwateXrThe^ for 23 h.. T, he, mixtuxe Was coQled o., T and : partitioned b. etween. EtO, Ax c, ardnrateraT ; e .,,, ; ; :.. s _,.. ..., organic layer r was, sqpjqtated,, washedivith water, then saturated.. a. Cl, soluton, dried-over,., ma nesium sul ha''tea d oricentrat Pk : d invaeuo : ' . resiue. vas t keri u . iridiefli 1 ether Jae. a y. ,' ; fi ! , i : l. T... t r.. . ' t.. ya - ;.-r-L, a a.. , !,' : _. , Ken up, in, le.., y ether and some nòtidissoé, <wås rërmövëd ; gX i~às'tiSd ùnder was stirring witch 0 25 ml of 3N F3CI ; un MeO and stmung was continued for 1h : Tlie solid that precipitated was filtered off b'y suction"and dried in a high vacuum to give 138 mg (69. 7%) of 7- (3=rriethoxy-ben'zyloxy) =2-met. tipl-4-pyivolidin-1=yl-qui'noIine'hpdioclil. oride as an light-yellow sblidSPass spectrum' 224202 : 349) :-..,,., w. . L. 4a.. lJi. ; _i -is, s ? : i. r (. :,. t. 3"T.. ,. ,, i"i'i !, r.. w n.,...... >, r ; q $ r_ i. í ; r J ì x, Y i < itv ;,,", ur, r,,, + ; a l rt, i,"9, r"i. r'^ :, t l r.'. » iT r. > quinolin-7-ol with e,, pprE3tine,. ..--'. 'F : jScai [-n 1 ; t > ti . r"a. . .',...... ,-t, 1. n, , , .. ."'.'.'-.'.-'... fp ; :.. j'''ir' ''. ,''-''"""'-'"' , . lx.. y.. . i... I f 2 R-.....-. . y . x., Y 7 y, E... In analogy to examle 6, tl_iere was iepaied on reactioi of 2 miethy 4-, yzrolxd. m 1 yl,' uiriolin-7-ol-wi methyTnodiie, 7. i"eho =, 2 ni, Qth 1 4: =', rolidn 1= 1 uino. irie,

hydrochlbride as an ofp-w&ite'solid. YSP mass spectrum, m/e :'243. S (M' CisHisNz : 243)., r.-,.,,... -,, .-,,. ' . ,',, .... :., : d.-. f . ....,, °t r ;..,,' methyl-7'-.' (pyrii#n- mass spectriam,, Ii :, 320'4 4't'e-d"f6 OH2 320 7 : 2 3, In analogy to example 6 there was prepared : on reaction of2-methyl-4-pyrrolidin-i-yl- qumolm-7-Cl witn"2-pic6lrcnoride, herebye ; p a's &ee'baSe, 2'- methyl-7- (pyridin=, 2"ylinethXy)-4 pyrrolidin. 1 yl-, quyoline as. : a_liglit broYvri ; soli : I, SP mass spectrum, m/e :, 320 4 (M+1 calc, ulatedfoi C2oH21N30 320,)... t (M calculated-for Ci HoN 'Exm"ILI, lq In analogy to example 6 there was prepared : on reaction of2-metHyi-4-pyrrolidin-i-yl- quinolin-7-olwith aHyI bromide, whereby the prdduct was isolated as free base, 7-allyloxy- 2-methyl-4-pyrrolicliri-1-yl=guin"oline as ligellow solicl : 'EI iriass spectrum ; izi/e : 268. 2 (M calculated fox ClH2oT ; O 268) .'r >> at. . _ ,. w ,. ;.-,.,,.., .,. ; _,. : >i. _...,...-r :,.. ;..... ''"'"''. % r'.''-'"'.'- ! .,, ''''...' ''". r. (M. apl&ix- ......,,-..... In analogy to example 6'there was prepared : on reactiort of 2-methyl-4-pyrrolidin-l-yl- hy&Tochloridjz : d, , a white 6lid,'ISP mas'V.-rq T hydzachloride ; as a white ; solid :' ISP mass ectrum, s. m/e : 285 : 3 (IVI1 calculated for' : CisHz4Nz : 25).. 2l'S',,., #rnpleÍ ; l. <,. e ; ; i _. 7.., In analogy to example 6 there was prepared : on reaction of 2-methyl-4-p quinolin-7-ol with 2-methoxnybe, chloride, 7- (2-meth0xy-benzyldxy)-2-methyl-4- pyrrolidin-1-yl-quinqline-'hydrocMorideaan ; solid.: IS, P, mass, sp, ectrum, m/e: 349.4 (M+1 calculated. for C22H24N2oz2n 349H)

Example 12 In analogy to example 6 therewas ; p : repared : on reaction of 2-methyl-4-pyrrolidin-1-yl- quinoIin-7-olwithtetrahydrQ.-furfurybromide base, (rac) 2-methyl-4-pyrrol'idinl-y-7 (tetrahydrfr as a yellow-brown waxy'solids ISP :. majs. s spe'ctEum, ; [n/e3 ; lBt2 MM calculated-for'ei9H24N202 : 313). Example 13,, fi1'". ;.,.', N.,, .., _,.,,, :. a,. ;' t".. _,'". e_, . ..... .., . .'ej.,, i.'' ',.'.',.'. . _..' ;. ;...,".., Examle, l3.,,, _,,,.,,.,,....,.,. : :....-. In anal. ogy ta examplew6 there, was prepared: an, reactionof 2=methyl-4-pyrrolidin-1-yl- quinolin-7-ol with of 4-methoxybenzyl Siori 7-(4-methoxy-benzyloxy)-2-methyl-4- pyrroIidin-1-yl-QuinoIinehydrochIoride as, a. light-yellow solid. ISP mass spectruml mle- "Yl,.....,... . :. tu u_tt : :.. i :,. fa'. Iw.. r. f : 7iS.,. : . ; 4 . =,. i. ,. i- y. fk. .. :. f.,... v ! 3, ;,, fj, v. . . ., _. ;'S.. : ruz E 14 - \ :.''-'r'', ''-'-'"7r.'' :'' : :. ,..,.,. ; S,. :. a ; f". t', ,. : : R ;.,, : w. -.. t.,'R. .'' L' : k. i' :. . . ;, F ;-. ''' Example. 14. ........ . ......'-.. :. _.. : t Exariyle 14 In analogy, to example 6i there wa$ prepared : on. reaction of 2-methy. 1-4-p. yrrolidin-1-yl- quinolin-7-ol with 2,-bromomethy, I ; benzonitrile, . whereby. the product was isolated as free base, 2- yl-quinQlin-7-yioxymethyl)-benzonitrile as a brown solid. ISP mass spectrum, m/e : 344. 4 (M+l. calculated for C2zH21N3o 344) t :, i ,. 2 rv.,', ;. ;. s , 3 a. a,, > i e i |. i",,, r R t ; Ä i ; S q ; l rr ; T o i ir :- ;/e, T .. \"'"-'. ;. '''''L'-''-' Bniple 15', ,.,,.,,,... .......... ......... nJ,. y.,, F,, >..,.....,, In analogy : red ,. E, , t ample 15. In analogy t0iexample. ; there'asprepared'. uinolin 7rol : th, bxaniomevth ;, -berizmt. rle wheeb. the :, rcdtc. t : . v. as. isalaked-asfree :. : , y :..., :, .. :, :., : Y : p.. base, 4- (2-methy=4--pyrrolidm 1-yl quinolm'7 yloymethyl) b, enzonitrle as. a brow solid. ISP mass spectrum,, m/e : 344. 4 (M+1 calculated for C22H2lN3O : 344). 5 ExambleAq6 ;,... l. iS i, l',' !', *6s í @ _- _,'..'t1. 1 ,..... 4.. v, 1 t, s". ^^, t... , :. ; . r. . , : i'.,.... z.". h-a., _.. _.. . ".'' ;"". ; u !-. '. ; , . Exampl6. . H ' ' . In analogy toiexa ; mple-, 6 there waS. prepar,->d, : ex ; e-actioin o ; f methyl-4-pyrrolidin yl- quinolin-7-ol with 2- (trif ! uorbmethyl-)-b6nzyl\chlo

trinuoromethyl-benzyloxy-quinolinehydrbcMdridea m/e: 387.4 (M+lcalculated'fbrC22H2iF3N202 : 387).,...,.,..-... . ,, F, .,,. ,,,,,,,..,... _... that In analogy to example 6itEré'4'sp^r ; épåred. oii rèaSU oX'methyl'4-pyrroliiMn-l-yl- qumolin-7-drwith'of3- (trlnubr6iitethyl)-ben (3-trifluotom'et4) 71e1, 6y spectrum, m/le : 3$, 7., 4, (M+ I- i, Ek=, e , ,.. : f L .,.., t,. ...''T v... u., In analogy to example 6 there was prepared : on reaction of 2 methyl-4-pyrroli, din-1-yl- quinolin-7-ol with of 4= (trifluororriethyl)-benzyl chloride, 2-methyl-4-pyrrolidin=1-yl-7- (4-trifluorornethylnzyloxy)'-qumolin&hydrScM spectrum, m/e ; 387. (Mlcalculate,,. i.,. ,.-.- !, tex , ., _...,, ."'"'''/&nb9J. , .'............,,..... In analogy to example 6 thete-was prepared : On reaction of 2-methyl-4-pyrrolidm'-1-yl- quinolin-7-olwith : 2-tMorobenl ; chloride,'7- (chLojo pyrrolidin-1-yl-quiolin. hydrqcMoride &<a ISP mass spectrum, m/e : 353. 3 (M+1 calculated for C21Hi1C1N20 353), ç,, t g eq, ^ ;'et r, 84t, % r JrX s ffiss-2]-s J t if ti} ,,,, r '..,,... _y ;. S^r.. ; .. -. dq, # T1 xn"t : a. ''-,, ...,.. .. t i'1.. ; ^ S r, L-a;, eExamle 20 . In analogy to example hewasprepared :- : pn quinolin-7-ol with'3-cMorobenzycMoride7- (3chloBO-benzyloxy)-2.' pyrrolidin-l-yl-quiholine-hy. io. Gloride solid. ISP mass spectrum, m/e : 353.3 (Mf 1 calculated. fòr C2íH2íClN20 : 353),,

Example 21 Example 2I In analogy to. eca, mp. le 6, lo, ere Was prepared : :. kcn, r ? eaction, 4f 2, methl-. 4-pyr. rQldy, l,. yl- quinolin-7-ol mth 4, chloobenzy'l chloxide, 7,-z chlpro benzyloxy 2, methyl 4, yl- pyrrpltdm-l-yl-MpIm. hydi : pcQyide : a$ 353.3 (M+1 calculated for : 353). E-xamDlt 22- In analogy to example 6 tliere ivas p, repared : on reactiori'of 2 riiethyl-4-pyrrolidin-1-yl- quinolin-7-ol with 3- (cMbromethyl) pyridinenydrochIoride, whereby the product was isolated as freebase, 2-methyl-7- (pyridin-31meth6xy)-4-pyirblidin-l a 4. T red solid. ISP mass spectrum, m/e, 320. 4 (M. +lLed fcr'C22H2l% 0 : 320). -'f T f rf f fS f, S, ; ¢i j i, ,, ^s Gi i L Ft''1 Sl ; si'f f i Å,., i S 3 , t . ; 31 ,..,,'_. !. ., 5n rf y, ? _" r"x. f 4.'t. _T.. I. ,. _., Examle 23. In analogy to example 6 there was prepared : on reaction : : of 2-methyl-. 4-pyrrolidin-l-yl- quinolin-7-ol with 3-bromomethyl benzonitrile, whereby the product was isolated as free base, 3- (2-methyl-4-pyrrolidi-. 1 ;-yl-quinolin-7-y, loxymethyl)-benzonitrile as a. yellow solid. ISP mass sMctrumm/e :. 344. 4 344). , for N . .., ... ..., x .-'1 :.,. .., _,. :. : ,.... : .. ° t.. :. it _. ... : 7 '=t rt.' : j 'ti.. i ... . r_ lc.' :.... r. . r'It.. t,. :,.,. a. '... c7-'."'' t ; a.. , _ . s :.. fi a.'-'> ss <i. :. . id., 7 .. $ta. e,. t'_a ; i-" n. n ; , _. F". i mj..'". a ( ? :, l. :.... _, _,... ., :..,. . ..', . t '. thym, ,....,.. s. ,. n t '. . _./,., ta n A k d.' L' w1e 4,, , , n. .......,..,,,,. hydrochloride, as a light- Im anal.'og to: exainple 6 ther was grp, ared on reaction of 2 nie. thyl 4-pyxralidzn 1-yl- yltqW.-.. so id,. : ISPm ; iss rum, m/e : 271. 4 (M+l calculated for cl C17H22N20 : 271)...,,''',.' 7-7- 'tfr,. 3< ; t., e. y.,. . t us° : Ii.. :"T. i. . p..,. i, i ss. y.. i.,. u r ! t X8I1371P . J'' In analogy to example.. 6, there was prepapedpn'.'reaction 0 (f. 2-methyl-. 4-pyrrolidin-l-yl- quinohn-7- : ol-, 6thoky.),-2-methyl" i : t pyrrolidin-1-yl-quinolin. hydrpchlpridg 287.2 (M+i calculated forC1H22N202 2$7)

Example 26 In analogy to example 6 there was prepared : on reaction of 2-methyl-4-pyrrolidin-1-yl- quinolin-7-ol with 4-(2", chloroethyl)-morplolne : : hydrochlo. ride, whereby the product was t-rn6t-p4ql, silyl) isolated as. free. ,,,.-. :, _, .. ... ..' -., t.' u . ; 5, _, ,, : n : t. , r... ;.. my .. ; k'. a, y, amle 27 :.'.... ,.., _ ,.. ; ; ,.. In analogy to example 6 ; Siere was prepared : on reaction, of 2-methyl-4-pyrrblidm-l-yl-. quinolin-7-ol with 4- (cHlprdmethyi) pyridine hydrochloride, 2-methyl-7- (pyridin-4- ylmethoxy)-4-pyrrolidm-l-yl-quinoline,. ; hydcHpride lignt-yellow solid. ISP mass spectrum, mle : 320. 4 (M=I calculated for CaoH21N30 320) ....... F.. .... ; r'_ :).. , r : Y',,-Vr. . :- t% s ;."-'a < a....-.. °r ;,.,. iFi ? v. u.' :... T : Y," : i... .. ; _. .. :'T,'ir. ixt.,. : >'., :.".. r 7¢ tz. f ; >'i. ; Gi-} ; r. l,. r, ibs t i ; >'i eh t. f"; $ : 7ì.. . ;--1S '''.-'.- - ; ExampIe8- , L ,-j-. ... a) A mixture of 436 mg (1. 5 mmol) bf7-BenzyIoxy-4-chloro-2-methyI-qumoline, product of example Id), and 1. 75 ; g' (15'inmbl) of (S)-3-emoxypyrrblidine, prepared according to Tetrahedron Lett., 1995, 2745, 'was'heat bath temperature) underah argon atmosphere for 18 h an : er ; which time the reaction was completed accordine to HPLG - r.-- ! .'. ? ; c T : . . i : . ''a. a. :. , ta !, . :- ii.... ?. L ; I e"'.,..... . 1 : ...,... _. f s,. , yE_ : a. ;,.... rlt1s e, r ; X rf 1-res ; r î5 1 V ! ; _5Ss partitioned betweenlEtO and water. The layers. were'separated, the orga} ic layer was'''' zu partitioned betwee; EtOA, c and rater. Te_layers wrere: se aated; the or'a ia layer was'' washed with water fihensafiurared NaC solutiori, lried over magnesiumsulphate ana ° corí'eSt'ra'tèd in : v'äcuiö.'T9e'residüe wäs taken"iüpXIn Mé'OS"dStëwitS i'èffiyt' edier (3'0'ml3 and'eMted''dròpwise : ai : R « ind'er'stirringHwithiOf i ; öf-bS ;'H'CL ; í'nw"" concentratedih'vacub. Tlie residue was taken-'up'ih'MeO (iml) duuted'wif diethyl' ether (3'0n)''and'thenreateddropw MeOH. Thesolvent'wasrembvedandliheTem washed off by suGtionndd'Eied l a higuitb giv&. 42S benzyloxy-4- (3-ethoxy pyr, raldip. : l ; l) methy, , qu. moJ, in. e, hdroc, hlomde ; axfaygt,, yellowsolid. ISP mMS spectrum m/e :-3, 63. % ..

Example 29 A solution. of 93 mg (O. ; 2mmpl) pf (S)-7-Benzylpxy-4 ?. (3ethpxy-pyrrolidinr-. L-. methyl-quinoline hydQMpr-4q,.', pr6'du-ct of, exaiftplc M, eQli was treated with 48 mg of Ell, atrnrcojD, ch, a. rcoai, (10%) andt, hyd, ro. genated atW for. 1 5 h until HPLC analysis mdatedecompletion-of the. re The. catalystwas nifered off, washed with water. artdthefSplutipn wascpncejtrated in. yac. u. p : The residue was triturated with n hexane/. diethyl efiher ihe soli, obtayed, wA s filtered off ; b sutionand dried in a Y,... .... :. ,..."..., y... high vacuum to give 67mg (90, %) of (S)-4- (3-ethoxy-pyrrolidin-l-yl)-2-methyl-quinolin- 7-ol hydrochloride as : anoff-whitesplid. ISPmass. spectrum, m/e : 273. 3 (M+l calculated for Cl6H2oN202 : 273). . ,, ../r. c''- rna-' ; . ;. jF. <<... .,,,,, .,-f l F/.... 4 j',. .,......., quino. lin. : 7 : . : : E t.. 1 w.. ; y.. i' : 'C'v1. m.. ''", . Y : ! _.. d'. , f,. u1e2' t.. o, . n, t".. : 4...-,... ... _ . hloride, ther tained : :,. pyrr6lidi"n-l-)' thq zy .....,. :, ^t. ? 'I r ; .'., s_ !..' ; y '-Y, a, Ft, , ; aiGtr-S. ru'ji i , eth. x'ni :, y r r s ;'a' A rj ;, ? :th f ; :l . a' was obtained : (S)-4-(3zethoxy-pyrrolidin-1-yl)-7-(3-mèthoxY benzyloxy)-2-methYl- was obtamed: (S)-4- (3 etliocy, pyrrolictm . yl) 7_ (3, methoxy=benzyloT)-2-meth. l. quinoline drochlomdea's a white solid ISP mass ; spectrum, m7ey 393. 3 (M+1 calcu. lated st, $ 44 i t t s ti, tt ; iS if, t,, \ i ? 5 ?. i : i. 7 > r for C24H28N203 393) r le 31 .. i . ;. t, j,. _"t' n a'., : "_."'. I, 7, y aj. "... _..... -. Examle 31.,. In analogy to example, 6 ; : on zeactiori of (S)-4 (3-ethbxy-pyxrolidiri-1=yl.)-2-iriethyl-' example 31 '': .'''''''''' ''''''S.. ''''''''.-.,.-.;'''. quinoliri1 7-olEydr"ochlòrJideróM : o Q 4% r, omòmethy ënzön-itrile .. -me y q yloxymethylj-benzohitruenydroc therewas, fi tt b+ t + ; i di @hé'tkW-pyrro umòi ; ínt t., ,-uM,. e , x s n- or Io r efih l -berizonitrI h drochloride as'a elo : w'solid P riiass s'efruri- mle :' 388 : 3 Y Y ,,, t y . : r w'u, r : ,, p,-, , , ,,-. = (M+1 calculatecl.. for CZ¢TrIi53a'38$,,: 5'°z; i z .. , a : r t'°'. F., ; :. : Example 32 In analogy to example 6, on reaction of (S)-4- (3-ethoxy-pyrrolidin-l-yl)-2-methyl- quinolin-7-ol hydrochloride, product of example29, with 2-bromomethyl benzonitrile there was obtained : (S) 2-L4- (3-etho.- methyl-quinbliri-7. 7 lo eth 1 =benzonitrile hpdrochloride a a l t-. orar e solid : I$'mass ; s ectruin, m/e : .. i. _. :,, ;'d'^. t- ; c i. _. .-.-t" r ;". q, 4d 1,'VF :-. - i. . j i°i r..,, . y' !... y '-. ».. 388 : 3 (1V+l : elc. ulagdfo. rC24HzsNQ2 : $8), <,.. ; .-,.., :.-

Example 33 a) A solution. of a) A solution. of lg (3 07yrrimol) o. f 7, beyzylocy.. 6 butyl, -chloro-quiiolxne hpdxachloride in 2.5 ml (30.7 mmQ].), pfpyriC (H (iine, a. s heated at. 60°C atmosphere, for, 24 h. aftei wyc, ttimei the, reactio rvas coinpleted ac. corelmg_to HPLC analysis., The exces pyrrolidmeiwas eva orated off, and the residue was artitioned... . :.. x,. f... k'.. ....... . ; p,,. ri. .. between EtOAc and ; water. The layers were separated and the. aqueous laxer once ectracted ..,,. :. . 1^'I, '..,, j :,...,.. ......, ..,.,.,,. . r. i.,' : ;, with AcOEt. The combined. organic layers were washed withwater. then saturated NaGi.. solution,. dried. overmaghesiurn sulphate and cphcentratednyacup. tp give 1. 12, g (97, 4 %) of the 7-benzyloxy 6 butYl, 4-yrrolidm 1-yI-quinoline, as a brovn oil. ; ISP mass spectrum, m/e :-361. 3 (M+rcalculated for 24..,- Preparåtion ; o fiels, tW ia S ;, i fZs fS--rK rS ; Otf ßiS ; J S ft' s l,"', .,.. .... a,... i. ; ,. _.,..... 3-carboxylic acid (prepared. n'onimethylbenzbquate on ester'hydrolysis with KOH in ..,..,... : : . u. l.. ,.,.. ......,. \.,. :,. '°'. .',"F' yY't.., ^ i i'ayFe. fL.... t_r.. w 4>. 9t'.. . , ,, el.- e y, ; s. . 1 .., iT :. i .-_ i.. b) A susension o, f, 1. 757' 5 mznol of^/J=ben,'lo-6 buJ y'l-4 oxo I, 4 (7'h dro 7, a7. ainoline- heated for 1 h at 200 °C. Theblac reaction mixturewascobledtp'RTSpof 3-carboxylic'acid (prepared, rozn,: methyl benzoquate on ester, ydrolysis mth KOH in EtOH-H20) iii 9 il bf quinoine was treated iyth 7 mg, (0 9 mmol) t of Cu pokdei and heated for 1 h at 200 °C °The black reaction mixture was cobled to"RT ;, 80 ml of diethy,, ., 1i : r.. ; sv T.. ; . t,. r. s." ;, ; eli', :. : s. : fz' F ; ;'< <"a., ether were added and the solid whichprecipitated was filt'ered offby suction. It was thën taken up in 100 ml of MeOH, heated to xeflux ; and filtered hot The filtrate was then,, concentrated in.. va, cuo., The residué was triturated vith diethyl ether, filtered off by'suction r o and dried in a high vacuum to give 966 mg (63 %) of the 7-benzyloxy-6-butyl-lH- quinolin-4-one as a light-yelloW solid. ISP, mass, spectrum, m/e : 308. 3 (M+l calculated for C20H2lNo2 : 308)., V....... c) A suspension of siQQt 2 mWtt t6Xz +tmoliq 4 1. 44 ..'^, . 4. si . y. ; c. t. r- :, t £,. : 1,,'.-' 60°C for 3 h with stirring. he' ! reactiun ..,. $ y.. r... , , r,., r. ,,. t s, r, ;., : i ,<. :.. ?'..... - e. c) A suspension of 9QQ, ng= (2 9 mmAl).; o. f 7 benzyloxy 6 l3utyl l.'I quinoly. 4 one; ih 1.44 ml of POCI3 (15.8 irimal, i: vas txeated iVith 0 074'rn, l of Nl.; dmne, thylariilzne and heatd_ at 60°C for 3 h with stirrm The'xeactiozi: rnixture as, then . bureelsizto ice w.. ate and'stirred for 0.5 li. The slid'vvhich'ieciitated:'as. filered ob _u. tionvvasheel: Wr,. at r. aW clried in a hn vh vacu: um ho: '4 ye'. I: flS 99po = f l-: eri.,.. 4=ch1 rra=: u 'e .,.. y, ;;/, o f b.,: ocY 6 bu. tyl o. q lnolin h drochloiide a ii ht ra:: salld: I' mass s ectrun. m4/e°-. IvI+. l calcla. ted for,. . ° L °' _ C2oH2oClNOr325. M)

Example 34 A solution of 1.02 g (2 83. : znmol) of tlie 7 benzyloy 6 butyl 4=pyrrol'idxn. l-yl quinoline, product of. example33>41'., e', 5, 0, õf 2, eO W+, 40. 33 g if, pládißm on charcoal (10%) and'thn"hydrQgehted : atR analysis indicated the completion of the reaction. The'catalyst was futeredoff, the solution was concentrated in vacuo and the residue was dried in a high-vacuum to give 0. 65 g (82 %) bfthe6-butyl-4- pyrrolidin-l-yl-quinblih-7-bl as a light ybtsb. li. ISP mass spectrum, m/e : 271. 3 (M+l calculated for GIHzNd 7. ),. E. :,,, , 3 4't r.. 4. '.'.,. 1.,. calculated for ... .,'..... : ... i',.. ..,.. n,..,.'.', . c''Exarrile 35'-. In analogy to example 6, on reaction of tnj1yP-4pyrrblidin-l-yl-quinolm of exarnple 34,. avith medé'cPRoride therëv ? as obiamed ; 6-buterl Sedi-'óxy ; , a : 285. 3 (M+1 cålciateifåWi O-85 Z.. ; 4 X ç 2Zi2ii'Z7-r s.'ít'l'.,'''/.'4i ; 5';'i.'.'. 't';'Zt tha- Z, t ; iiL X, i, 8,, ; 5e å'^ 2Za Z ~ ; ~ ;''X''' 285 : 3 (M+l calizlatezt ; fcz ; ClBHz¢NO : $S) : ;., . ; ; a, ; k k : : j r .. :.. r i. :. _.. rs ;' c :. :. f.., . ...... . _,. _.. wir"F. <_....,. .. t' 2.,. _ W. .,,. ; .',.... . :, :,...., ... .... r.. f... .., i_tcu. i. .., ; 'v.. i :,. l.. .. eyi,, a n., l,..-M,,.."t. . f) ; l. 1.,.. 47k ET,:, t t9Ht t. In analogy to example 6bnreactibn : of 6-butyl-4-pyrr. olidinl-ylquinblin-7- of example 34, with ethyl iodide chlbridethere was obtained :. 6-butyl-7-ethox''. pyrrolidin-1-yl-quinoline hydrochloride as an amorphous yellow solid, ISP mass spectrum, m/e : 299. 4. (M+1. cålculatêd. iorQ : 299. 3. +., ;', ; t,- ;-.'1 , a o.. D...,, ," ;. : t. t. : ; . y,.. a. :. k_k-, ; ta< . >'', 4v't°"t. ., ;.. 'F iv, v : 1, :" (... ___27 : ., i.--.) ,"$.., a'. :. t :. .. .. r ; v t , r, ; c a t,. a e-6'i ; W,.., N : ;', r., n. -e,., . '.". iY : iv. 4 ... o, a., ^ j..., _, e !' :,., 1-0t : l. _. y. sis.,. $anzri 1, v t_... .. .". _, ... .. - : r.,-.',. ! _,. t vt. y a .. W 1:., , . _. L<. Sr A m. T .. Er.. j d 1, x Jtii.;, s. 3E. ssf. In analogy to example-6n'r'eacNoNof-6bu of example 34, with brbmbmethyl cyclbpropahe'mere'wasbtained :' 6-butyl-7 ''" P Y Y.., p I ?, tY cyclopropylmethoxy-4pyrrolidin'-l-yl-quiRb hydrbchlbride as'an off-white sblid. ISP :.,., , S,. j,..... ". mass spectrurri, mle : 325 3 (M+lv'calculated'ffl'Ci=H2$NZO : 325) :'° '' '' -t. Exam-o e, 38' "-''''""''"'"jac h. vdrcj. :'f."'\- {ExampIe3. 8 ! '/tt-it\s \ : f='l'' ',.' : :, ; d, : ! SP i<,' :'-''''.' In analogy to exaiiiple 6,''oii rection o6 tiutY 4 pyirolr. in 1 yl-quiriolin-7-ol,. produtt of example 34 ; 4'-liiomorriethyl berizonitrle'tMere'vas o'btained 4=6'butyl 4=pyrrolidiiy-1-

yl-quinplin--yloxymethyl) benzQni& light yjellow". solid., ISPrna. ss spectrum m/e : 386., 4 (M+l., XcXated for Ç25H27N3. 0. : 386). :,,,. ..-.".. i..,",...,.. : :..,,'f f ;,..,. ,, y as,. 38. 6. 4 fgtiQ-2. 5H27N3Q : 3, 86)..,. ",. S xarnplef 39 ; S k . ; r,., :.. m.. ; ,. , r' : ...,.., a A s. olution. o£2 : 1. 5. 9 ziirri^1 of 7-. en lo ; 4 chlozo--mth 1 uinoline,. a xo, duct_of , ,, O ,, y G) y : , . ' Y : Y q,.... ;., p _, .. a.. _ example 1. d), m 15. 5 ml,, (0 137 : mo1)."of hecamethyleneimine wa eted a.'t 120 °C-, (.. oil. bath tezin erature. with stirriii'uder an. ar on atizios'here fo. r 100 h after yvhich time : the :" . w, : .. _o _xc, :. p.,., RT'and then part. itioned between. EtOAc, and. water,, The layers were separatedßthe agueous ,", ;,,.. FP,., _ g,,. : _'... . y_.,, :,.. r. ;.,... :. . _ :,. 3.. :,.. toc layer once, extracted. wthAcQEt.. The cp,. then satur-tecl >NaC-l, olution czied". : er.. mar^ e ium sul hate.'a r dF : oncer ted u : V. acuo. , a a a,, ;, T Y, v, , s P :. : tr , diie, d,, y.., acuo. The oUyiresidwastdissDivedms under stirring with 4 ml of 3N HC1 in. MeOH, The,'solvent'wàs remóved'in. vacuo, the. residue. tr. iturated w, ith.. diethyl ether, under'strryg fo : 5 h and the. obtairied solid filtered ofFby, suction. and dried in a high vacuum. (Further materaal as ohtined on evaporation of thfe filtxate and treatment_,. methyl-quinolinehydrQcMqride, J, 46.-g. (55 .,..,.,-t ; t °. tMH f,, ,. s.. C'. m E >. aa., F, ;., : 7 :.,- _nL."la. r : r '. :.'J,- ., ', 5 1 y.,,,. f. .-, r :.,,-r... t. _ : methyl A solution Qf 1. 45 g (3. 78'mmol) of 4'atérfan'"i-yl-7-bèrizy, loxy-j-methyl'äüinoliné ,..... :. i, f ;. :,. ISP mass spectrumx. m/e. 347 4 (M+1 calculated, for C23H6NZ0 3g7), zu . ., , .,",.. . -.-ss : i,...,,.'_' ...., . . ,..-.. . .. ,'. _, o 5 ; r. " r v.., p"f,', W., E R o s : ( t . .. r : r , a'pir : "<y : a x"n r ,. t ! Y,, : $airiite 4a' ; ° ..' . :. ; 3.. ,. ,, y,, , :, " ,. ; 5, _, a t, ', 1 ik'sr. Y, ^C'i s .. ; i,'.'t 1. . H. : . .'1,'-t'r, ' . +... iz§ i '.,., t Y a' a,, y5".., 5. . ;'... A solution of 145 (3 78 mmp, ) o4.-ae azi=1 1 7,-b, e'o 2 meti"1 uinoline u 5, r hydrochloride,, prpductof. example 39, dissolved in20 ml ofMeOH. was treated with 7, 00 . A !. :', ;. i.. ....., ,.. ; , x. 1-,, r i 6 ;... a a *i,,'k rs-, i.. d' r' : c ; , .,, n, . .". t P..., Y ; tt.., t_, jtY,. : ?'....... mff of » alladinm bn °caicoal (, 10°0) ancl then : h droenated'atrRT forv2"h until-HPLC analysis indicated thecompletion of the jeaetioh. The catalyst was t w PS f ; rS ;,. tfÄ : ; f'?., P. w Ae} X,., jf, VE,,-;, f, l i. ëï t fß r 1. water, and the solutipnwas concentrated in ya. cuo diethyl ether, the solid obtained was BIteredoSbysuctiPn'and o'sive 1 g ether, (90. 4 %) 4=azepari-1 1 2-inetkiyl quyolm 7-0l li'drochlorde as a liglit gray solid ISP f mass spectrum, m/e : 257. 2 +1 calculated-% r Ci-'''"" I. ; m , i7 mass : spectrum, m/e : 257. 2 (VI+I calculated for ClsI2oN2° 257) : , w . S., < :,.' i s, :, . i, =,. 1 . .. , ; na'_... _ pg, y quin6 in '.. ,. y.. ,,, _,..,,. .. '. : 'i. : ... ; , oh _ : ; Exariile4T ;, _. . °. _..,... I a s. i ; t""NY. .,'12. f'r. s : FRa..,. 7'. t..". , o,' h^, r t. n.. rdt... . a..". °,. u-.,. ' :. e... In analo7' toexample, 6 ; on, xacion o : 4 _az an = lf'nieth 1='Q uinm oi > > ; : ; ,. : J'. :, tT,......, x, z. r t... ii A'... : 1 t, uh. u , P ' _ ; 4t lY, i, fl4., . ?.'T S". x a"" h drochloride,: rosl. ut:, pfexam le 40 vd, t: =. hloioziieth l , xdneh. dr. QChlaricl: e: tlieire

was obtained: 4-azepan-i-yl-2-methyl-7- (pyridin-4-ylmeth6xy)-quinoline hydrochlpride as a light yellow solid'. ISP mass spectrum, m/e : 348. 4 (M+l calculated for CIO : 'L ; i f 37 t ! etf, ; ! 7-7 j-- 348)..,. ,. s ; _. r,. :. .., :, .. 'In analo to exam le 6 wori., reaction. aof 4 az1 an=1-11=2-rrieth 1='iiinoliri=7-ol -w - In analogy to example 6pnreactiQn hydrochloride, product of example'40, with 4-tromometliylbenzoiiitrile'there was :...,,. w-P,.. s" ;., Y,,. :, : s,. bbtamd : 4- (-azepan-l ;-yl2-m as a Iight yellow solid ISP mass spectrum, rri/ 372 : 3 (M+1 calciilated for Ci4H25N-30 : ,, a : _. ..,, :.. : 373),., ,,. zur 'of 4- , t..-I .. 1'. ,'k ,.,'j e'.... i'.... .. ... p... ;. ! ;,'x r, y.. lI.... , 1..,--5, L. i.. A1 ; :. ;.'e.. ^w. ; x'.'".', y m. ,. (.,... a4 ..... 1. W x t.. ' ...'...' ? i , <... ni :',. _.,.. ;' ''.', .. .. _. i i t 1'.."m' .. ..." ; , y F.',', r. :' yt-... .. yfi. , x 1. 1. i, S 4., rS.... : f.. r. ; ils thé ré vas .'i4 : , , _, r. _d : r.,,, T., fs ? ' t'1... 5 ; °. ls j, ; . . , m.. ,' .. .. In. analo or'eXam I6. oinne c'tion'of4=a e n =. 2=in th- .,.. gY, ... x...., p. s. x, r.., . ; Pa. =Yl. , Y. : qu nolm. ; 7, , ,, . i I, 4 ,hydreGhl6nde,, product df example 40 tl 3ro'm6methyl benzonitrlie tn. er. e was f 4 7me4yj,,, q zu : obtamed : 3-'4. aze an=- .".'-°-r.'.-, < ! :'-t'-'t. K'....'' : u : '., f . ; Y l",, y... '. Y,.., . _ t't __ ; 1'we r. c w ;, In analogy tq example'6, Qnjeac t !. ! i : ; j In analo. t: an ,'Ie 6, von reaGtron. o-aze anv, I- 1=2-meth. l-: mnolm 7 ol, hydrocMoride, product, ofexample 40, ....,, p Y. pYx. t ;, Y. _. '.,... : ; ," {,... : < was obfamed -e'an 1= 1 nieth : 1-7- : : xdm 2=s, lrietho. um-line=h. drochloride ..,.".. P,. Y. y,..,. (1 ? ' y,, xy) :-... .. Q. y.." , °-,, '. as. a li h.. e ' : t. Y. llowsolr, SP. mass, spectruin, m% ; e 48 (1 calctzlateItfortzHzsNO : 'JO) d-'' : '.. ; r.. ; .''0 1 sF. , , k'. c'.'Al.. ; ,. tr' r7, ..'.,.. lt... t. s., i'... 1; i1.7'i t A,,. t , s. ri '. t 1 "Exaniple 45.:;. a) A suspensioji of 1. ; g (3 ; 5 ; rnmol) pfbromo4-chlorQ-7-mehoxy-2-methylcguinpline in 20 ml of EtOH was treated. s. equentiaily at RT and under stirring with 0.49 g (7 mmol) of pyrroliclme, 137 137 g (1. 4. mmol) ofpyridnie'aTtd'cat. alytic amount ofNaI. The mixture wastlicnheatedr. eflux ! &rr2 was fihen hatedbt. r. eflc: for20. h, cooled o:. RT . rid. cocentxat'ed vai; uo: The:, due

was applied to a silica gel column with CH2Cl2/MeOH (7 : 1) as eluent. Combinations of the purified jEractions and concentration in vacuo gave 6. 85 g (68. 2%) of the 6-brpmo-7- , ., , w" y : ° : Hi. v.. x*iMLf... 7A..,. i 7,. iaSi,. Ct... _. eY, : uf : . yI : wl' »'t uN'L, t. v-,.. er 56, e.. ' meth d Preparatión ; of thé stàr. tHig rnàtisrial : - :.--t'''--'-. . Tih. Preparationofthestartingmaterial : - -...-.. ; ;,-...-.'.-...--". Preparafiion of the star. fing material. 1,' ..-,,..'.,. b)-7. 66 g (37. 9 mmol) of 4-bromò-3-methoxyrphenylamine. (preparation. described in Tetrahedron Lett, 1995, 753) were dissolved in 80 ml of cclohexane at 70°Cand subsequently treated under stirring mth 72 mg, (0. 38 mmol) of p-toluenesulfomc acid monohydrate and 4. 93 g (37. 9 mmpi of ethyl acetoacetate. The solution was then heated monohydrate and 4 93 g (37 9 mmol) of ethyl, acetoacetate.. The solution was then heated e ! a : dY. °'" ;'" : t ;. :,, a,,,., a. -, . y. a_. 1. '-, i''_ . . ;, ;.. : c,. gave^8. 2t 688% §ii itirfthe't6Z) 444-WoinS4S'rnetWp, hzeä, mi'n : o-but-2-enoic'acid k 1 otcentrted? inauo... Thersdrewas'a lied td. a'sltca eI olu. mn, ithvexne/dieth 1 ther (3: I), a-elent: Conibinatoms f'ehe urifidv. fracCmns anclvCOnceyratlori: invacuo ae: 8 2=-. (6$: 8°l0 of. tFie. Z 3=. -brnzn =iietho hem. lamiiio-but-2-enoic acid ethylester, as a yellow ; solid. ISP riiass spectrum, m/e : 316. 2M+1 calculated for Ci3Hi6BrN03 : 316).""""'''".'...' . i : ' ; 's''s2v....,... i t..". t ;...', T) ; ..,..'i .,,...'. t. ;' c) A suspension of 5 : 6 g (2 mmol-) of (2 3,- (4 romo 3. inethoscy-penylarW no ; but-- X. ; ;'I¢ re < 4lS ; e/4, irg-'> eS ; 5-. o Z enoic acid etli. yl ester nn 40, im1 ofDowtlierrnAwere. hated= : understirmn' at ; 220 °C, for7 : 5 : tg h after whlch-tlmetLG ahalysls ; mdicated cornWi, etion. o'ge rea. ic, tion, ?. ihe mixture : Mra, $, u "il r r r vei, tz i et s I, : S ; <4 nf cooled to RT under stirring and the solvent was decanted-oft. Theremammg solid residue . g. e i"> rF titrG irt 3 ; i. M'í'i,-,-"e., r. si. ii S ir 0 i ; was triturated with hexanenlteMdionby suctioh and dried in a high vacuum, to give, 4. 7 g ,.. > ;. .. ; w. y.. _. _ s. :.. _r. ;-. ,-= ; , ... f t.... i.-d. j : s...,..- t.... .," ; i. :,... 1 _'m :, z ;,... id,.,., a , s . 3 rv, . ; k :"£. , . ; sh tf 3-. ., , ,.. t.' : °' . :, G.. . y ; s, r ih. ro . s --. % a F '' !' , r,. . t r F....' (84%)'ofme : 6-bromo-7nethoxy-2-methyl- C13Hl6BrNO3. 316). spectrum, nn,/e : a69.-t calgulated for, iRlorNlo2 22699w,, ; ; 1, L,, + :,.. = : s : ; :.. .,-aW,.-, t.,, , c.. z. ck.,..,) .. k_ns.,., . :.. l, i,", . $.,. ;,, .,. : a.. . <. E, ,,. t ;.. i... ;. , : 6.. 3. tA-. >. r6,. 'e-r r : ; y. _ .,. pli. ; °t 1n,. _35 '-,.,. f. v3. : Cd ; Va4. y. ;. : t t .. _r P. 'T. .. Fi : ^7v : a 1,."_ t. :... x : ...,. _,. __r . _. . 5.. . .... a, w.. a. if : : i. 4, ;. ,,. z yy,. r.. n ; r. n a-s6li (a. resiciue t f 4.. n't : , ;'v i ;. _ 5. :, m.. _. a. ,. a :. ;', : af (^ ; °.". k.. k., a s. y ; : f'i'. NLai.. i i<... 7 w. . i7.. . ,. _. . a iS : vas d) A suspension'of 4.6 g (17. 5 mmol) of 6-bromo-7-methoxy-2-methyl-quinolin-4-ol in , ° ;... xY. ; Y (58, m 0 3 was heated at 60'C for 20 h with stirring. It was then cooled to RT. and 50 ml odiethyl. ether were adde,. Th, sol, id that,. prec, ipitt, e, d was. lteed off by ¢, i ; rEej ; ; 14'r ; § tt'; ^ £-*'- ; i,, 1 e, ra, ii ; r . ft,. ii suction. n. ti'ihe 6-bio,-it. orb-7 ; rp6thoty-2- g vac b methyl-, qum, oline. asajdar grownsphd. ; EL massspectEum, m/. e : ;. 287' (A calculated jrpr methyl-,. uy, oine, as : a dazl"br, own, soln : EI mass s. ectru °'m. e : : : 87,, M. caluTatec', for -, qula . Cl°1, H9BrC1N0.287) t

W. T Example 46' A solution of 115'mg' (Q : 32'mmol) ! 6f6-br6nlo-7-idethb : -2-m'ethyl-4-p quinoline hydròchloridie,'cömpounld of ieYL'Spe,'was'dis'soldediim'S nSiiofd'ry''CH2CI2 ; under an'argon : atm6spherend. treated. dj6pwis& ,., : ;,. ^ x CHZCIzvith ice coolmg : ft 0 :, 5 htlie icbath rcvas'r. ezribyed, he sol. ixtibri. ivas sfiired. forw 2hatRtahd'thenheated-tP : reflux'] r -., w se e, aqieous, ...,. Y, :.. 1 ?. ,. 4 : Y, further ertracted yi : th CHC127MeOH-°mixtures (8. lv)., ;. ; ; , w :.,,... _."'', vacup. The residue : was ; appliedl : 0iasilica. gelcpluninwith vacuo. The. residue : wasra lied. toa slica... el colu. mn mth. CIiCl2/IvIeOH : 151 asvluent : _..,. Pl ?, : f),...,. splid. lmassspectrum,/m/. 07 ""-7tl b s 7J Wt>n « t- InL antalöogyt teW ii ; ; ea) tioGbie o'Sa} flXibF r. e as a light brown :. solid:. ISp.. zn: ss s ectru; tm/e;.. . 0 2.' (. I+l., c cl_ated for,, Ii Br O 307=: .,. e t t..' y: I iExa. mvle 47; In anaTo te=°, a:,::; onea'. na'=b 24, th l.. < .. idr. s. _,:'ri gy c nsp. le 6y. tio orria rn y 4-pyxYOl, n 1, 1 qm olin-? =ol hydriodiRoride, iFirSdbEt of hå'&les h =hzönitië tiere wasß obtåined :-'(Sbron nieif seoli : din9il.-yl-qumolin-7-yzl ; oxymet, hyl)-, benzonitrile as a li h ellowvsolid IP, rnass : ectrum, nie. 424 :. 3 (M+ : I° cal ;'eulatezi : for ,, ; 3oBrT30 :.. solid. 424).-w :, ; . :. a. Ez :-. _, r 1_ ; x., r,,-,.. a. _ : -'= . .,,.,. I a i 14 1 6'g--'y,-6, "e x'ia i, n-p i'e56 1 ,, T , aE to i 6-- 6 r i i 6ih p ;-y r, , o'I0 61 titi u... ^°, r k. e.-... i. C S F.. : : G ; x,' i. .,'i y ;-, :'.. ,,.. a... _, s s, :.. ,. _ : v , .' : :, z. _ r".,. _,,. 1....,.., f :. a,.- :',..... _.... = x= .. Y. aY. _.. r,., r. r. yExaz 1e4 ; 8. .. f' ; ; 2 ,- ;,, _.. ra...,.. _..'. f <.... X_t,. h'. r. _. . f u. < :. :..,,,,,..... e_ ;'t', ° ; 9 ; z,... .,'., i. ,-,.. ;.,',., , 1. t, a. r. ,., ,,. °=t _' obt ; ained, 4 (, 6--bioffi6-'2--iith p7T61lidin, , 1,--VI-dtiinolin-7yoxypet4yl)-- enzonitrile of isopropairol-sva'sr tur, etted,, widrßil 30-ìr. 83 r tnt4WyrrOl, ort'e. ànd Iheat t 6 i£ for yrr., 6-h ; -The'.. i,, 6'ac'tion-, rriixtur,,,, "nez J'.. n' n a lieci'to, a: silca: lcluxnCl. hXa. e/AcOEtrl as=eltiett. : li: iznfied,. fractions: r: out. The filter, *, 4-,., i ,'a_ u o,-, mvet, 48#1-2, LO/c (). out. Tlie c ;'stas : vrea filee of arid : ried, na . hi auurn to°_ 've_, iiz '2'. °, lar : ro 7 _ : :,. x'S'..,, ; ... - _. ...), _ n l, g"'ol methpquinolyt) sg'-penyl'u mass spectrurn ; m/e 243 : 2 (M :'calcuraed for CslH, 1N30 : 243), r . 4 _. : s = ; =, ., ., :.., :.. : . ;.'p a...., w. e ! x _-.., t'' , ! ,...,'. °, i.. . , 4 li) Above sec startizig'iiiaterial vas"bbtarne"cl: tirin rhmerciall aaable. 1- (4 chloro=7- metli'ory. 2 cju. nolyl).. -peryI:-rea. (500Ym =. 1d53. m. rn. al) <nn EaCinguri°. a solitmn; o: f...

isopropanol/THE/GHzGlz (30. ml :. 20, ml : 20. ml)-and m the presence pf217mg (3, mmol). of pyrrolidine Jr 1. 2 h, at :. 60PC ;. =UpjOn cpnc product a....., _ :-,... ,. product e, ry, s, tallized out.. t wa , tered off b ; y, sucti'o, n. and dxied y, n a.. hi h vacuurn, xo. give. _ ... Ft ;., : : :...,. t., v,.,. :, ..,., r ; __. r,. ..'-r.,.., 250 m (78°./Q) of, te 4-chlxo, Z,. metha-mnolin 2.. Xamzne as li ht br. own, salid, ISP v..,. ri d,. h mass spectrurx, mle Z0, : 1 {, (M c, alculated, or, CloI9C1Nz0 20).. _, ;.,, ,,-....,. v x.,.'t, , q :.'1'',....,, . w..... e. 1,, n, T,, o lid., ISP . .. . .') . t.. _'.'R, ... t,. t, a _ s ;. Y... tl. l. u''.''... ... e ? ;, , t, , .,. : ,,, .. . ..'.. » ,... :.. neo , ExamIe 49 In analogy to example,, 45. a), fom 4 chloro-7 metfioxyquinoline (synthesis described in : J. .. v,.. ..... Med. Chem., 1998,4918) andpyrrplidine there was obtained : 7-methoxy-4-pyrr () Hdin-l- yl-quinolin hydrdclonde as a yellow solid. ISP mass spectrum, m/e : 22. 2 (M+l Y q.,. ;. .,., Y . : f ,, g,. y,.., : . . :,. ; 1. .,-s . ,,., calculatedfb. rCi4Hi6N20 :'229.).. .'..'-'."''-",... it. t .,,,.,,..".. ', ; _ fi txT 4. ,.. ''"'''"""''""'''''''''' :''''''''" :'' :''''-.''"Example'50"'""""'"",'''"*"''---v"-."."'...-.--.. : ; Examle 50'e, >-,- In analogy to example 46, from 7-methoxy 4 pyrrolidin-1-yl-quinoline hydrochloride and ,, _. on treatment with B. Brin'toluene under reSux there was obtained was'obtained : 4' pyrrolidin-l-yl-quinolin-7-ol as'abrown splid. ISPmassspectrum, m/e :'215. 3 (M-hl !. calculated-for,?-, t F s i,. cul . Iri : a. agy'o example 6tlere as prepard on reactior, o2 methyl. 4 pyrolidm, _-, 1- . :., . : . f..,. :.,.-. ;,,. ,. Y quinolin-2-olwith3, 5-dimethoxybenzylphlori. de, (3, 5-. dimethoxy-benzyloxy)-2-methyl- 4-pur, : : :,, ' , ', yE ;., a r ,, ; n XYa ; :,,.. . : .-, y. 4-, ^ rolidin,-1 1 tumoline h droclil xide as a. li, ht ellov. solid SP. mass s c umA mEe : ' , ,,. . _ 9 s , _.- S : '. ; ; , .. L s ; . z'', ; ; xx. y _a s 37 4. (M+lt, calculated for CH6N20 379a .. ,,,, in 1, 6 e'r'd : 6'ii reiti'o"n'rol din'-f .,., _ ;. _ Mr ,, 1 ;, ,, : ;-,,. _,. .. _ quinvolmiSI7-ol witfi ; 3', 4-d imeSoxXlöride, 4rvlìefeby'die p'Ti"cíSwås Wd åisfree båse, 7-,'4 dim, ethòxy-bétipxy) t 2'il, red} iyiL4-pyrròlidin'4 : qiS''ine ást t-yellow base, ;. solidJSP.'ass. sp. e'ctrum

Example 53 .analogy to. example 6 ! there. ; as prepared ; on reaction of. 2-methy : l-4-pyrrolidm-l-yl- quinolin-7-ol with. ethy. l iodide ; whereby thpoduct was isolated as free base, 7-ethoxy-2- methyl-4-pyrrblidin-l-yl-quinoline as a brown solidL'ISP mass spectrum, m (M+l : Y ; I ? Xr'. _ :-. Y, : 9.. :, : s--. : . : v , ; s. . ; . p : ;. :. w. ;... calculated for C'N20N'0' :, 2'5'7 _... a. :.... -. .. ... i :. : :. i.., s :- :. . . , r, r : ."n..,'..,, ,. ; .. :..'. v. ., t..,. k '_.... '..' : i i. ;. :. C'. a., , ., ! j E''X. :' In analogy to) le', 6. there ion, gf-2. 7m., et] 4. yj4-, p,, yrrolidin7l-, yi-, In analogy to example, 6 there ivas prepared on reactio, of 2-methyl.. 4-. pyrroliclin-. 1-yl-. quinolin-7-olth6-met] ol-2rc yImthpxy)-4-pyrrplidmJyl-qm pwhite solid. JSP, te ' ; : t. ;,. spectrum ; m/e : 334. 3 (M. 1 alculated for C2lHzsN30 :. 334) :,,, ."..,. : :, :.,., »..,..,, ,. I'anåioi-to. epléXthérë ; asiraép+, Xi't, önAtiqn, 4 » 'ere,, was,", p t y spectrum,-m,/e : 334. 3 (M1 ; cåiEulåtedf 34) hiS'--;,'''-X,,,'....... : ... . . t. ' , ;.. m, ,- :..,, r ,... , 7,, r, ; .. a.. ae ; i,.-. ;.. . -. -ji °t^"y, , !-..... ,.... j.. . ,. In vrialo-to, exam Ie 6. tlieie, as-r ared'on °r'eaction o2 m 1 _4= Irdm-I°. I-' gy.... p,..., ,.. P,..,. ......,..,,. Y,.. 1 ? 3'x''., _. X uirinl'in-7-0l witli. meth 1° ; hlor, oinetl 1-id'ire,, 2' : mexh r7. (2=meth, l idin-3- . _ . Y. R'..... _.. y.. y, : 1 ? Yr pyrrol . spectrum,-rii/e 33. 3 IvI, l calcuated-; for CZi-Iz334 33) ..,,,", 1 In analogy to example 6 there'as prepared : on reactibn. pf 2-methyl-4-pyrrolidin-1-yl- quinoiin-7-ol, c oro-3-chloiomet'i e, 7'07pyr 2-meth 1 4-sroldm 1,. 1 uinoline h drochloride as white solid. ISP mass. spectrum, y pYr 'q., Y, 354. 2, (M+ 1 calculated foi'H2Cl M/e : C2 354). a. :... . 5... 9. n 4,. , f-. L 's. : = _'S... n ;,. _ ,,. ,. r, ylP, q'.," t : ;. t. rx 1 ., . ;'£ i..'f ,. w,' . ; t,-.., ', '3. f ..'. - Exaniple 57 , a. In analogy to. examptetliere-was. pr. eparedx. p. p p4 _Ili-P"4"".. . quinolin-7-ol With.'.. 2 clJ, oiQ. , ekilQroirnethyl :, pxciye, (2 chlor4-pyridin 3-ylrizethoxy)- 2-methyl-4-py, rrolidin-lj-iSl-i. quinollne,, hydr :'ocßoNsiiTleXas,'wShit, e. s. iolid. IS, P>m,-åiss/, spectirium, m/e: 354. 3 (M+1, alciulatexitfW C20H. 20i, C, l4

Example s8" In analogy to example 6 there Was prepared : on reaction pf2-methyl-4-pyrrolidin-yl- quinolin-7-orwith3-cblpromethyl-2-nubrQ-pyridine, 7- , ' _-. z..,., 1 =C., i. x r . ; n a, ',.. :, . , q..- 1 ! . Y,. v. w.... '. I. aa. I 1, _....... P n. n... t... .. r : 2-methyl-4-'pyrrolidin-l-yl-quinoline hydrochloride as white solid. ISP mass spectrum, m/e : 338. 2 (M+l calculated'for C2oH2oFN30 : 338) r '"','. .. ;,, ; y,,. t'. i.. v.. ;. ?'.'. r,.. zxarreple-59 In analogy to example 6 : therea$'prepared : In analogy to exazriple 6'there was prepared on reaction o. f 2 inetlipl=4=pyrrolidln'; I-yl- "t,, rc, w y pyrr6ilai-"., i-yl- pyTidin-3-ylmethoxy)-2-methyl-4-pyrrplidm-l-yl-quinolineh solid. ISP mass spectrum ;, m/e 368 2 (IvI+1 calculated foraC2IHz2G1N30 :-368).-, ss spect. rum, V. 1., 2"I n .., ..,--. ' : ;. ? r. i. i,, l f q. t 4 r .. if.. S 9'e'r ;-oi .,'1.. .. yl i r ru <''Y.., A, : . . k r° ( 19 _ ¢ '" t'. Li'. a. : 5'i°.... : 3 : ? X,'. '. t"., j ; C 9 k...... l,. rT ; Jj t : a, -.'yl... M.. iti..., . , t.-... j'-,, a ;. u,...,., r' n _. ^. n,., , .. 1 s.. t. . , 2.',. t In anaogy to ecarigle 6 thxe, : as pxe. gard., onrection, of . m. e_f. yl ;-. prxoidxr, lv-, ., r ., ..'.,',. _ : ; t ;. :.- qumolin-7-6lwith=l3r0jmometnyl- product was isolated as free base, 7 (2-chloro=6 imffuoromethyl-pyridin-3-lmethoxy) =2- methyl-4-pyrrolidin-l-yl-quinoline as aitejsolidi : ISP mass spectrum, m/e : 422 : 2 (M+l calculated for :. CzlHi9ClE3N30 422) . E". ,-T, 2 r r 1y..'tT ; 4 'L}'a',.... 'T". <rs2,. _. ., t,, .". i ; l, t, :. °.. _, -. i , « i$. _3. F, j- :... '... ,..,,.'.,. . 3, °r.- : F. ifTLx 1_. u2 '411. k.... Fawc , , t),. : aWt,"-'. ! ., If7T"IY^r' f's"t'," ?- .., m, m.,.. _ L,., i . ... ^..., Sl'riiale : Si, ". t <x. r,. i d,.., ".. , y. .. .. ; "".'.'E,. In analogy to example 6 there was prepared on reactiori of 2'methyl 4-pyrrolidm 1-yl-, uinolin,-7- ; 0l wi, th ; 5 chloozneth 1 1-idne , caxbomtrile, 5, (, 2. =meth 14 ; : xol, id_in=1= q y pYr Y pYr I'SP'. mass'spectrumm/e : t345t4, M r'''''t"-f--..-''-.'y ; x, ;. uflb .. s.-... i ft n, ; 79 s ! ; Exampië62, ~." 't,. r : i ,,'yJ.. y ., , f... ISP: mass. rspectxuri;; izai/e. r3; 45,4 (ItI+1 cal. cul, ated,'for CiIl4C? a. 35): _.., _.. _,. b,. . : ° : 's : o , ' Examle 62 r. In analogy to example 6 there was prepared on xeaction of 2 methyl 4-, pyznolidm l.-yl- r. z'. t e J r ;"f-f', g r.-: f.'~h ç ~ i'i'5 . t l 1 ii f quinplin-7-ol with 2-cMoro-5-cMoromethyI-thiophene, 7' (5-chlpro-thipphen-2- ,. ! iRtis fi'd,..- {'_,'-D,'5i ì, <. rd tr"'t f, 5, <fi-, j {,. $.', ef, ifí7X,'s. t Zi 0¢i4,,. jt'. ; ; sS ylmethoxy)-2-methyl-4-pyrrolidin-l-ylXnõlSthydróchloriide as white solid. ISP'rnass y)-2-methyl-4-pyrro speetrum ;-m/e 3. 5, 9 : 2. (M : l. calculated f. ox (%. i9nClTz, . a9.),.., i'.

Example 63 ,., In analogy to example, 6there.'was prepared : on reaction of 2. 4-pyrrolidin-1-yl- iop ene,'2-m6tb' : I"4 1 yi-, 7- (thiophen-3- '. F, ^.,. i i,',,... . .. : s r n . o. inl,, ylmethoxy)-qumdline hydrociilonde as wKite soid. ISP mass spectrum,, m/e : 325.. 4 (M+l calculatedfox Cl9HaoNQS 35) .. . °'$ . : £ : N'. N2Q r. s, : ?-w, _ ; = 1".. d, . ei, ';. Examile 64° p...,. In analogy to example 6 seize was prepare (l :, on'reactiQn. o quinolin-7-ol with'4-bromobenzbnitrlle,. whereby i&olated, as n-ee base, 4- (2-methyl-4 pyrrolidin-1-yl ; uiOriolin-7-yloxy3Xb ! enzPii$litri ! easåwhitesölid. Isprnåss spectrum, m/e330., 5, (M : Fl' 3'30)"' In ahaligy,, to !', 4''iih6ky,-p,) irrbl d methyl- ...,...,,-. r_S,,,.,.. s''^,. ', l. r. 0.-1.. 3 . . . : d,. : "t i ta ; : .''., '.. : . . ... . w. a. _. L ; . a..,....... _.... n x ... , n :. i ,-t.. u 'f . r,. t r's u I" y In analogy: toexamle 6a-on ractor of (S) 4 (3 e. thoxy-pyz'rolidm, l,-yl)-2-methyl-' quinolin-7-ol hydrocnloride, pro, duct. of example 29, with. 3-chlorom. ethyl-2-nuoro- idine h drochlorde. there as obtained S 4 3-etlio rolidin-1 1-7-2-ffuoro- PYr y E) O-, xY PYr Y) (. idin=3-lrnetho) 2-rizeth 1-umoline h drohlarid. e-as ; a white solid :' ; ISP-zass- PYr... Y. 'Y,., q, Y . t.,.,, "...''.,'. . . ;'...,.. JExample6,.. i.,,,.....,.. ,..,....... I .. v. Z :) :' : a' : : FS..'°". ... ., x1. 1 :... t"'j. ,',. l'r 4.. , 3 :' : 2G. tr ; 'e 1 i. , fn.. E_. . i, iw. _ ;.." », m., r '. . P ... 1.'i,,.... ., F 1.... »....., t, 1.., !'i.. ... f4.. . ; r, j. i f ; t) : e. :' rk) wj_1.. °. t.... ,. c.... :.,.' ,... . lle.. _.., , .. i,. i.. .. i..., 1 w. . 4 Ix a'V d jv, 7.., _.,".. t , Examle 66 ion- Tn amalogyt, o exaiizple 6, yon rection o (S).-4'' (3 ethoxypyzrolidW '-: yl 2=meyl=,. umolin-7=dl li drochloridei'roiuctbf earii le 29 wuti2-cliloro 3=chloroiTiefii l'v'w 'pyndmehydrochilozide tli'e iv'as obtamed, () 7,, (2-chloio p ? iidm 3 ; : ylmethoj-4- (3= ., =.., , ...... : pyridihe hydrbchloride eie'as btainedr. 3',. Y :, , Y : r.,.. spectrum ;'m/e : 398. 4' (M : cdculated.. for : e22 3 lif., ^, 3yri,. f 3iie"'z, J 43fitr ! _- 33, ^tí^-=ì'3i3Jt^ i r-133 Eiihi e i''H''^ s 1 s j « ; @-t 2 í e t'i X f ; '' !''EXi nple 6 7 Li, i,-M In analogyto example 6,'on reaction of (S)-4-' etloxy : yrrolidin-l-yl)-2-methyl-, ,..." <, : ; , t , ;,.,, p,, quinolin-7-ol hydrochloride,. pioduct of exzrape 29, mth 3 chloromethyl-pyridme . :'. ...,. s...,,,,"

hydrocMQride, therewas, 0 ! btamd : (S 3-ylmethoxy) :-. quinoline, hydTochlo spectrum, m./fe :,. so Mass 364. 3. (M : : ;. r°., a, b : 1, ° ; ... = 3. 'fx'f'_. i,., '°.. _.,... !. t n Exanij .........., :. v.., b : i, ;'',, . :.. 4 : r f... t 1y.',. : T', '. : 'r , .,',.,.. _ i. ;'1 ;' ? .. 3. :.'. : ; F'u,'^ :..,. 's_. ..'. -... i'..... . .,. a.'., ! : r. ^, :.. r. ,. t.."r :'', j. lTt.-St°"- ;.. ..', r. w s, ,, ^, s- .., t", _ po ., r l.,,, e f ,,, Examle 68 In analogy to'example., : onea'- qumolin-7-ol hydrochloride, pfoducfof example 29, with 5-chloromethyl-pyridine-2- i' :. s_r 5.. carbonitrile there vvas obtained. S) 5=4 (3-thoxy-pyr. rolidm l=yl)-2=rriethl-qiiinolin,-7- yloxymethyl]-pyridme-2-carb6nitrile hydrocMpride as an off-white solid. ISP mass yloxyme yr p A-mass, a : ;, : : i. 23. k 2 r a. 2.. l, r e : _.. r t-f x ? f,- .,,, J a. V"t i- , :, Y 4,. t t. °,. 9J s. Yr 1 .".. <.- _. 'Exan''It'le 69" In analog. texampleopreatipp of 4jazepan-yl-2rm. ethyl-q..,., ;. x-ethyl q hydr, ohlride"product, o : eam, le 40 ; , nth 3-rnetl, o bei 1 chlorid therew as. obtain. ed : ... :. :. :... .,... . ;. ?., : r.. , f :., ',. : : '. ; q :. =m....-' :. .,. __. 4-aze an=l= : 1-7 3, =iretho. tieri lo'2. ziye , umalirie l, drochloride. as. a : li ht'E, Y., .. Y,. zY.,. . y.. r. _.. _. ' q. r. , : ;. Y-,... yellowsolid I'Si ?.-máss ; spéctr, ums>m, ke. 3T, 7. 4-MS cålbul, åttei<2S, 202-.. 3. 7r8ì ;., ; ^ In analogy, to ."......, , - , '"''./, -' ;." :.. : . ;.'. .','.''Example7b. ' : °,. "-"'.., . i.-i".. ! .,. , Examile 70.:' In analo to exam le 6 on reacfipn of 4-aze an-1= 1-2-meth l.-uiri 'n- c vas hydrpcMonde product of example 40, with, 2-brom obtained 2 (4 azepan 1 yl-2 niethyl-qizzo yocymethy, I) lienzoriitrIeliydrocliloride as an o sòlld ; L ; iSP<qt'72 3'q+ ; i0+90 : 372)- . as an off white solid : ISP mass s 'ectruin ; m/e : v 372 3 (M+1 calculated ' ( r C H N O : 372. "''"''''''. '"''''-'-''''''. "S4''. --. at- A< ;.'. K ; . ' .. ; 1. ,-s [, y-. :. #. L.' f t ., ,, ' b , r't1 , I. y : i S"A . : . rz.. In analogy to example 6, on reaction of 4-azepa-l-yl-2-m hydrochloride, product of example 4b, with 3-clil6r6benzyl chloride there was obtained : 4- ,... r,. 3'.... f, ,.. i 7'. tt ;.,. i ;, : s........ azepan-l-h't'yell'ow ^, as aug solid. ISP mass s ectru'm". m/e 38"13 ; 1VI+1 calculated, for G' H. C1N20, : 381. . ; .,. p...,... : :.,. . _.,. r,......,..., 2, 3 25 :,../... ;.

Ex'åmple, 72 In analogy to example 6,"on reaction bf'4-azepah-Ii-yl-2-methyl-Quinolin-7-orr ; ;.' .., '.,."7} _ r, ;. ; 4n . . i. , : 4t'i, ; . : a.. . f ?' :., i ! e,.. t . . _., i'.. hydrochloride, product of example 40with 4-chldrobenzylchlbride : there was obtained : 4- qxy solid ISP zilass, sgectrum ; y. m (e . 3. 813., (IuI. l,, calculated. £or,. 3H25C1N (J 381 ? ;'. -........ , , ., I :-.,, :"y,.,, , _, , ;, t _ j j,. f.. A, i .. ,.,.., ,....... ,...."... A suspension, tof 98. 5 mg' (0. 2-5 ; mmol) oii 7- (6-chIpro-pyTidin-3-ylmethoxy)-2-methyl-4- pyrrolidin-1-yl-qumoline hydrochloride, jfo'dSct of example 56, in 0. 44 ml (5 mniol) of morpholinewas. neatedundenitrpgen at-6p, °h (o 72 h at 100°C The. mixture was cooled to RT andpartitionedbet\veenEtOAcan . 5, ., t^il.., a T. :,.',., ; : v'-m .., j, ; ... ,, «. i .., 'The: oT"aiiiclayer nras, sepaxaed,'vashedl; WaCer, °tdryd: over=magnesiu cetate: and corice'ritrated ;'in : vauo Thesicluervasvakeri°upin ether' (20 ml) ; tnsolublematerWfv'vas'=, x ;,,. .,, y,,"r., remXõved'by'futr. ationi kd'*ëit'Xe. treätedRÓ. l-riof3'-SH'Gi li^Mè0H, hëtsólid''. Y . , ,. s a high vacuum and then' : applied'toa. toj5ilicagelT a hgh vacuum acl then : appliecl'to a, to sl, ca gel, coluiiy th CH2C12rMeOH-/. iHOH . '... 75-t^,. : (19 : 1: 0. 05), as'eluent. The punSed fractions were c and concentrated in vacuo to a small volumetheri aciclified : by. adding a few dros of_3. N HCl in IvIeOH.'The sQlverit vas taken off in vacuo to give 23 ; mg (18%) of the desired 2-methyl-7- (6-morpholm-4-yl- d"6i h pyridmi-3'='ylin, etho} =4=pyrolixnt'l'-yl quiiolqne°iy. oehlor-itle asalight yello'slid : p _. , ,., lisp,, ectrum ; l. inle : r4b5 : ' IvT4=1°calclaedforC24agN4i :-405) : '. . r, -,, : c < ,., ,, zu RiT>dilutëdQtSenethylè esXI9ri& (. iiO'ièn^^ërëdThtë ä+4t'eiw : ås-fi^" dx l ! 5 6 f ;-, r,'= Y 9..., J, aMghvacuumo' .. t. t, ',.. Fr. i t."., <',-A,. , e'i y, t -' : l. S.., i. 0.... : Fi (. , t t :., ^.'i i.. 1". hL. h_vSn>. .. , . ° Examle 74 , e, R.,.., 4'. f... n. dtY. i Jr r. 3. : F A,. : X : ! t M j. _ A-N.. h -A i '. f,. .....'. , i $ ; J ^nl, Zi-i'-,. v.,..'°..,. f . tF' ,"1 :."} , '. Tt. i,.,... :".'4. 6Ai. _ia, ; a. : v :,. 0 ion : [' ;...", i.. ; ; i..-"i5.'j .,'a ;. 1s 7 : s". ,.,.', "_ xa..',. A suspensaon of. $5-mg°' (d : 25°mmol) of7-E6=hYoro-pyividin=y'lmerxjmvlil='= ., r. a : v :.. z : : :... : . , ,. _ . T,,,.. r.. a,. n ; ' >x.. .. f. t.. r, '. '., p. ;.. y-, . r u,''. pyrroliclin-1-'yl=qW iioirihgdroch"loricle ; rbduc"of-example56 ; 1-rrig (7 : 3 mmo)-of 'BINAP; 2: 8 iig 0.'-O1 rririlo'1) o': Pd (IF) acetae;;, and. 9' rng' (T-iizrizol)-of scdium tet-butylate intoluene, (4: 5-mly'fas''eatecatTmtht36ring (0: 5iiinl) ofpyuiblicrneridtlln=- heated a'xeff'ti uicler anargorir. anospherfor 4h'Iiie ieacfiion-i"re was-coele'ci to : r RT; iiiiutecl v5ith methylene chlorxde (10 rrtl) '; and=hierflti'd: . The: filtatvasv:. concentratedyln° vctio; thesi'tle trituratecewithet'kier, =filered ofb 's'uctibn ai7: ried in ahi fivacuiiito: i, $rn"v8% ofe-2='me 1=4-, rolrdn. 1- 1=7'-6--'roiidiri=l_ g. g g C. ) Y PY'Y PY' yl-pyridin-3-ylmefliaXy).-quiriolime as a w. hate"solid IPviass; sspectrni; m/:: 389: 3 ('IvI+1' calculated'for CHssNO : 389).''

Example 75 ExarnPlè 75 ^. ,.,.,, ;. § : . ; Jei1 of exarnple 2 ; ; 71 img (A.'5S mh-ol) öt'3''dimetWàrmri-ö2 di4~ProAlii967 mg (0. 75 mmoI) of triWpinei'in THF'^ Vmlf'wå't Wie'åt''wt t39@0. 75'i ; : - ;., ;. ; r, y 4, 3 t,'' ; ° ; : t.. :, .,,. , of exarriple 2 ; 7, 1'rng ('0 53 iizmo° o 3 dimethylammo ; 2-. dime'tyl 1 propanol ; 196. 7 mg r . r (0. 75 mrriol.'of triplienyl=phosphine W °THF ('4 ml'vas treated a RTvvith 2 . il'0 :'5 . E",,., ; '", jazz :">..."'". : ., :. a ;',.' ;-"7.-. r. nr'', r,. 5, r. mmol) of'diethyl g"po umn,, *ith. C- H ..., ( : . ' 1, v : t. ,, iL,,. . formed was removed by filtration, the filtrate was concentrated iri vacuo and°the oily ;. resi, d, ue obtalrxed wås'+ed ;, tö is. ica'gW +. CH2CÌ2/MeÓi Wo as eluent.. The, purified fracion's were combined and concentrated, in, vacuo :. The. esidue" was taken up in ether, the crystalline solid that formed was. filtere. d off by snction and dried in a high. vacuum to give 24 mg, (23%) of the desired [2,2-dimethyl-3- (2-methyl-4- pyrrolidin-l-yl-quinolin-7-yloxy)-propyl] dimethyl-amine as an off-white solid ISP mass spectrum, m/e : : 342.4 (M+1 calculated for CgHlI3O 42). (Further material, 30 mg, 29%, was obtained on concentration of the mo of the product as t.,. j i,.'tL 1 1 7'. 5. : dr. , llyc, 1101llOtel2' Scilt)",' S ;->'_ t ° z.. L . : :. Sr _." _., i t nr i' f i ;"i..".. a :.' In rt eri R , t t,, ^e 571 t is r,. a ? t., < ;} "r ;,. arnp e 76, l s it, I.. I-^o. 1', s.. ^, yt., m #" _,.. ilz.' :' ; ay.., , ia#'. M rr. ,.., if'S ir tf. _-"3. ;'. '.. ?.". : fr _. (4JA C ru : 'Example 76 In analogy'to'exam. ple5n, rectionX) f 2-m'eihyl-4-pyrrolidin 4- h dro' 1 iiieth 1 i'ericlite th'ere'was ; obt. iiued 2'= : intli'1= ( : 1-rnetli.' ='i eridiri=4=''- Y Y. y P p Y Y.. P, p _ _,,.,,. : . : i.. . r, , r -. f :.. ;.. 2, 7,. «'%"t 5$4"; t%/ft j >.. « iala >'s d i''i'^n. ~"t Y Xy pyr y q . :,. p... calclilated for -aoiT3'26) : : , t, n-. ; a"a. , ,. : v w. : , a . « : ;. : f, 1 . fixarnle 77 , , 2; s ° ts In analo'' tn exazri'le 75. on re. ctlon of2 meth 1 4=''roMdxn=1 1-iiuol'iii-7-ol'lrith 3- gy p. t, , , _PYr, Y q., liydroy-tetrahydrofuranc thereyas. bbtamed: 2 znefliyl 4. prroliclin-. 1=yl-7-ttetiah dro- furan-3= lo) quiiioline as a li'ht yellow Qlid ISP, mass s ectrum, iri% e"299.4, (IvI=F1' pyrro, i, , iq cdculated'rti8H22N20299 A 7. imassspectrurri ; in 'F.,.', ^.. e_ca a,. ; :,.. ! _ :, !., : La,. S'b ,.'ta. t, y ; e ti., . 18 22 2, 2- Inanalbgyf6exa : mple"75, : 6nreac in anl"o'&t6 7 4'P'Yrj'qUiriolin-7-61--'iviih, '.'', i %.".'7...,.. sy.,. a, . t.,.. ¢., ; .. Jr,,, E.. :.., q. _ ;. . , = ; r . s. r..,,., t,. . 1 F . :.,. .'. y,, ; x : 'gxarrile 78, ;, _ ,..,,..,. !-"., tel. s. ! y pr : :' t-w :,'e, :.. Jf.'s,.... x.. _r'. 7-.. f..., .., .. f,' : ,,.... In arialogy to example 75, on' ieactio, n of 2 i'ne'thyl 4. =pyriolidm.-1 yl qunolin 7=0l, ^vtli 1-me'ti '1= : eridiri=4 1-ni'e, thzol; arid arx rsolation of tlie rticuc a h ci'rochloiel. e,

there was obtamed : 2-Methyl-7- (lTmediyl-pipendm quinoline hydrocmoride'as'ahite solid. ISP mass spectrum, m/e : 340. 3 (M+l calculated ,-for Cl'H2, N, 6 :'.'3 4 e r n" In analogy to exampl75,''onieacoR6f2-methyf-with 3- morpholin-4-yl-pr6pan-l-ot/and on isolation of t obtained : 2-methyl-7- (3-mbrphblin-4-yl- hydrochloride as an off-white solid, ISP mass"spectrumj m/e : 356. 4 (M+l calculated for r... I '. I., ; p ,.. .'. ......... , Example 80 To a cooled (6°C)'soluti6h of puy, .. . i. a.. Zi >., .'' : . x., ..., _, i,.... 4ai...'.. 7r, 4 °. tdS st.. .', i, . . ?.., 7., . L...,.... : . nun.. ,...,. °u n_.. : f, <, v [.. .. zu Example 80, ,-. To a cooled (0°C) soluion of 2A=metli, l, 4, 'yrrolidin . f 1 quinlin 7-=0l (97 rii';'3.49 mmol) in dimethylformamide (13'mlLade'<io<lium'hyd 60% in o'il, 168 mg, 4. i9'mmoi). After 30 min at 0°C ethyl. bromoåcetate (0. 5 mL, 4. 50 mmoi) was injected. . _". __..,. 4.19 minol): After 30 min af 0°C, ethyl bromoacetate (0,. 5 mL,! : 50 mrnol) was injected. e, d wcw, After 2h30, an aqueo'tis soluioi oNaHG03 vas azl: ed-ane. the aqueots layer was extiaceiVith dihIoromethaii'e. =Theloinb'ined'organnphaseswere'washedttli'biine = v aid water ^atid thed~driedrwscPdiuti siVet'A'-Rer iträ+ibnSolvents-Werereioved in a highvacüum.,'T ; het+-'e W sJ iêveXr-A+ ation-7"the7sb was ...,.,, dried in a'high vacuum to giye 660 g.. ( 60. 2 %) of (2-methyl-4-pyrrolidin-l-yl-qumolin-7- -y-quino : yloxy)-acetic acid'eth, yl ester as a light brown solxd. ISP rizass. spectruiii, mle : 315. . 4 (M+1 cal, ciilatecl.. forCi$HaaNi 315 : 4),... , ; : : ,. :. m..,.". :.' : : , r.. _ ; :-, ..', :,,., F ,'_,.. '.."'.', s '',.'... a' : y,. ....,,..... ethyl ester (613 m94e1ilc « iO@ai öaè (506n t (506'mg,'12-. mrrTReu - hydroExamle g', was washed with. M6 To a cooled (0° solufion of ( nieiyl 4=°yrolidm l'l iiriolm=7 loXy)'cetc acid ethyl ester' (613 riig, 1: 95°rnmtila}'rn. ethyl alc''ho (OF-mLvas >a. decI. sodiurii-borolidru (506'ing; 12: 4vmrizol Tlerttre=rv'as 'firr''ed 71i a'r'ooriirizpr. ture: tqu'eots't;:.. hyrocliloiide was addecl crefii'1M; 1 mL):-'T'-he-=suspenion w'as lefed ad tlesolicl. was washecl. wnliMeH : Thevsoluov-'vs. driedoercdWm :'s, ulfate, =lterc andthe ''= ; solvent'wåsSte'rtòved nR, å,'lE77S"-, ad, ûuiSi, t, o ; givè425~'mXi->, Os °Wr, i,,, 244, 5 tl^, , g, :). Y. : erolidim=Fl 1-uuoliri=7-lo': efharol as a lirovri oil. ISPii3a's's ectiuin in ve: 73. 4 (M+1 cålculate^d £or''G'3') .,... . r,-,,., : :

, Exåmple, +82,. To a cooled (0°C) solution of of 2- (2-methyl-4-pyrrolidm-l-yl (425 mg, 1. 56 mmol) in dichlorqmethane (20 mU) was'added triethylamine (. 0. 9, mL, 6, 49. F,. ;,. .,..,, .'_ 9^ : .,",, c....'. i-h : mmol) and tosyF chloride (lil5 mg, 5.85 mmol). The reaction mixture was stirred 22 h at o. , m, : $.. room tem erature An aqueous soluton of TaHG03 was 'added. After'separation, the zip organic la er was washed with brine. The brown ^ was triturated, mth dieth lether. ,, , was After fíltratior, the solid was dried, d. in. a high vacuum to giv, e 520 mg (78. 1 i%,) of toluene-4- sulfonic acid 2- (2-methyi-4-pyrrpiidin- -yl ester-as a light yellow solid. ISP mass spectrum, m/e : 427. 5 (M. l cculatedfo 427. 5)..' ;' ,...,,. '., F, w,'.. ;",..,,. , ..."y, r..'"W°., ...., . 7 , ',., A , t,.. .., ...., 1 In'ahalogyto exampie're was prepared : on'reaet ; ion'of2methyl-4-pyrr . e, y . s :, _-.-, f,'"y ; i : f. :. s- sp, e,, rumi, tm-t/e3'4. 8., 5, ; MÇ, aiei, 2E,, e''34. S). t-,,',-'s,. t, ; ;,, i, 3,'S Y I ?.,. P r,,.. :.., ;. : Y, ., : .. :-,.. _'a... yridin-2'1=' ropoy'), 4 'yrroeln 1 :-' l iiolme'-'as a-ellnw uiscous ; oil' Rrriass-,... specfruin, m% e'4 5 (M1 talcul; ated for C22-F253:'48. 5'-); ,, ,, Exam ^1e 84 Exam'7tRe 84-; *'.--'^ ^ ^- In analogy to example l, on reaction of 7-benzyloxy-4 chloro 2=methyl-qmnolme with ...-r, _ :, : _ ; , .-. morpholine, there was obtaxned °7 benzyloxy-2 methyl 4-inorpholm 4-yl quinoline as a.. waxyyeUow solid. ISP. mass spectrum, m/ ;..... : e.., . s..,.,...,., n an o6y.'i"o = s..,"=".. cA. _ .. -. >, i t. a-_. _fh, , s, ,it !i'>.-r.,-. ;.,.. n _... i' r. i.-, t dt fi , r, i F-1 rf :. ! 1 ;. 1 . r t'- Ni , t. ;.. 1 'M T. i t x..-t, , . T- . u _ .,. Examle 85 ..'ir e.. y ;. ltr ral.. l.'. .. .. dY+. s.. : r. t. yfr7G ? a. lt-. 1 '_t,. q, .. -..' Yy^ : , r... : ll y., rroilcLitie,' (2-, 5, ... 1. . .,'. t 7S., ,. t. <i,.. nr -, s i n... .. . ,, e --", s j,...- :., : d. ;.'' 1 S ; i : In analogy to'eXample, 1 : ;. owreactoof 7 liizyloy=4=chlpro=2=inethyl-quznoline ; nnth an ... f f Y, : y^....."SZ,..,' : i.. : F,.. i 7 ; ;, s :'. . 4 :",, excess of (S)-3 hydroxypyiiolidime {2-; 5moe-eqW valents). m,, ,-riiefifiyl=2-p. yrroliclone: as. solvent at 100°G, there wasobtauied: ; S 1-7=ben 'lo ='2-nieth I= uxzioliri-4 I:.. .. C ZY Y. Y g Y pyrrolidin=3=ol as a'I'ight b: own, soid,. ISP, rrass spectrum;:-m/e. 335.4: (M-1: calculated for' trum'. C21n22Xo2U2 335J

Example 86 In analogy to. example 1, o, n reaction. of 7-benzyloxy 44 chloro,. 2. methyl ; quinoline, with an . excess of (R)-3-hydroxypyrrplidine (2, 5rnple-equiyalent ; s.).. in l-methyl-2-pyrrolidone as solvent at 10, 0°. C, there was obtained : (R)-l- (7-benzyloxy-2-methyl-quinolin-4-yl)- pyrrolidin-3-bl as a light brown soM/ISP. masyspctrum,'m/e :' 53 (M-l. calculated for pYr., , g P C21H22N2b"2 : 35) pu6 87 _...,. _ .. excess o (S) 72 yin*1) , yrr, olidine (, 2, 5, mole-eqiiival nt In analogy to example 1, op reaction of7-benzylpxy-4-chlorp-2-met an excess of S-2-h dro meth I1 . r, olidine (, 2, 5 mole equivalents) zn,'1, methyl 2 -. . Y xY : Y ? pYr..,. :.. rolidone as solv. ent at 1. b0°C,,-there vyas obained.. S 1-7, ben l0 2-meth 1= qumolin-4-yl)-pyrroIidin-2-yl]'-metnanPlK solid. ISP mass spectrum,. m/e : 349.5 (M+ 1 calculated for C22H24HO2t. 34, 9) , i t, t ,'. . v... u.. ^tl , x ;, f 4, P..-'' _. G il ; . d 5r, 1.' C1. _ Z i"' ;, i 1 n 1". d° 1 5. Y Z 11 . o.. : . ..... n ' u.. 7' . In analogy to. exampleel, o. n reaction of 7 berizyloxx., 4 chloro =2 7methyl. quinolme, : with an excess of (S)-2- (methoxyznethyl), pyrrolid ; ne4 (2, 5umole, equivalerits) in, l methyl 2 ; ;, ; pyrrolidone as solvent at, lpO°C, there Waspbt (S)-7rbenzylpxy-4- (2-' methoxymemyl-pyfrplidinl ;-y-2met'' y ox 6. ethyl- ''-''cdukt''T ; d. : r''C- :'4''.. :'-''.'.''''''" .,. , r..,.,...,.. In analogy to example 2, on hydrogenation of tS)-7-benzyloxy-4- (2-met ....-'---', P''-'-'....,.. .'''.'' ?, ;-. ; ; n. ! ;.'. ;.- .. ;,,-d. : Z'-l, In analo f to exarri le 2;'ori h° dro ematxon'of'S-7-ben : lo-4 2 rriet'io . e'fh 1- pyrrolidih-1-yl)-2-methyl-quiholine, Droduct. of example 88, with Pd On charcoal (10%) in Y Y. : q ?,, P MeOH, ther. ewas obtained : (S).-4- (2,-M MeOH, there. was obta, mecl, (S=4 (2,. MethoXyme, thy. l, pyi ; rolidin'=1 yl)-, 2 methyl=. quinolin- MEOH, th-, qqinolin- 7-ol as'a'yellow''s61idSPas m : 3 : 2M. R :'" r 4 ; t .'^7 r', y', t, iv :, i, y : rt L'., ii fr ;. 273)..,.-, _' ', :,. _.,..., . '1 a i. j.. r,, tc,'. 3,,',.' ,. "t, t !, > , , . , Exame 90 _ f- In analogy. to'examplea6;', on ieactmri:, of,. (S. 4f (2 TVTethixymefihyl. pyrr. olid, in=1 yl)-2,:-:. metfiyl=quinolin 7=0l, product of exa'm le 89; mth 2 chloro 3-chlorormethyl-pyridine hydrochloride there was obtamed (S) 7 (2 chloro-pyridin 3-ylmethocy), 4- (2

methoxymethyl-pyrolidy-1 yl) 2. mettiyl ; quinolW e hydrochloride as a light yellow. solid.. ISP mass spectrum, m/e 398 4 (IVI+1 calculated for C22Ha4C1N302 r 398). . . . ,. : a,,,.,. r.... ; ., :.. _. w. _ :.. .,...... ; a k. ^,..,.'..,..,.. In anal. o, gyto example 6 on reaction of, o (S) - (2 Methoxymethl-pyrrAlidy.-1 yl). -. . methyl-quinolin-7-ol ; product. of exampl 89 ;, with. 2-fluoro-3-chlo, romethyl-pyridine hydrochloride there was obtained : (S)-7- (2-nuojrp-pyridm-3-ylrnethoxy)-4- (2- methoxymethyl-pyrr61idinLl-yl-2-methyl-quinoline : hydr6cM ISP mass spef'"lcgc'82) Zt Äw2taV",-f rExamwvlez'92 _, +,; Examlte 92 C,.', In analogy to example 6 ; on reaction of7 (S)-4- (2-methoxymet] l-pyrroH methyl-quinolih-7-bl,'pr6duct of example 89with cycldpropylmethyl bromide f hydrochioridè there w, as. obtåined : (S)-7-yc, lopro, pylmetho, xy-4-(2-methoxymethyl- . a.- Es : : ;,. :., :. :, pyrrolidin-l-yl)-2-methyl-qumplinehydrpcMoride, as aligh' pyrrolidin-l-n .,-. Example 93.' .,.. : ",..., f__, :, ,, ;, a,,....... _ : . ., yl), rpyrrolidin-2-yl]-jnediahol, product oexaSnpS ?, with Pdon charcoal (10)) m. °,',' : l,- :, f.. r A.'.. i4 ;, , c.....,,, l. 4. !'. d. t..'. z.. . _i'.. t. r Ly :. .,., i, ; ; ; i. rvx°asf. f.."x..-j . ,'v'x.. i.., . t. , t , '. _. ,...,-', . .. n. .. t....'., l. iF. . A t,... Exemple 93 2, n-iiinoliii-' In analo to. exam le 2'oii h dio enation of. S 1-7-ben. lo 2 ineth 1-uyolin-4- ., '.., p a=,-Y. , :. _g y., f,. ) .,,, zy xy.,, y. q a.., :,,, : 1.)-7rolidm 2 1J. rnethanol, , roduct bf exain Ye-$7, witi Pd"on cka-rcoal- (10% iii, Exemple 94 MeOH there was obtame: (S) 4= (2 li. dra etli., l-- rolmln, Sl,., l) 2-rneth. l ui. noliri- 7-o_asa ello solid: ISPrr. ass s exuiil me: 2 9 3: ,"1'calculate vfar C'H N O:: - , a 7 In analogy to example, on reaction of (S)-4- (2-hydr6xymeyl-pyT'rolidin-I-yl)-2- metliyl-qui'nolin=7-ol, prouct of-exaiiiple 9. 3 yt ; h,"2-fluoro 3 chloioiriethyl=pyridine' hydròchlóride Aere'XoSaineM it^s}-tòinß, yAèthoxy)-2-methyl- n., _ g,- uirioliri=4= 1-'i; olidn -. l-rnethnol as; ali ht. ellaw Tsolici.: ISP mass s ectru. rn/e: 3. 68. (Mlcalculated : @

Example95 Example-95 :, l s ; w In analogy to example pn reaction-of (-S)-4 (2-hydoxymethyl-pyrjbli'd 2''- ., a ; : methyl-quinblm71,'pr6dGt of example' ex hydrochloride there. was obtarned (S) -v {1 [7.-'_ (2 chPoro pyr, di-3 lrrietho. y) : 2 mefihyl- , r i ;. "t. ; : :., -, quinolin-4-yljr-pyTrpUdin-2-yn-metlian6l as a light yellow, solid. ISP-. mass. spectrum ;, m/e : 2-, hycIT, y I py r Example Gi5> In anal, ogyto exam : ple 6> on, reacton, of. (S) '= (2 hydroxyinethy, l-pyrrolidm., l yl)-2.-. methyl-quinplin-7-ol, prpductQf, example, p3- obtained : (S),- 2 [4- (. 2 hydroxyiriethyl , pyrroidm =yl) 2. =methyl-qumolin 7 ; yloxyrnethy, l : 1"benibh"; åj+|9+a'ssitrútk, 3XS', > 23,. 25, ; 9 a-. x d . : . ; --t.. ,.. ., : tn Ts ; r., . : r .. _ In analogy to, ex methyl-inoln''-"ol, h ;' I e ,.,.,.. t, j't t 7t . A.... . Z.. a>. SF r".-, j',, L" xU, C.. u Y v tn, <.., a. r'CSS.. ita n,. .,... qu P9. y -, p , .. f. ,,. !) Exàmnlê 98,'] ;--J . ie... , :.. In analogY to. eXample 6,, on reation of (S); 4- (2-, hydxqxyrnethyl,-gyr. ioldini, =1 yl) =. =.. methyl-quinolzn 7-'0l, prodct.'oexaiiiple. 3, th; 3 cilormetliyl, pyividye;'tlieiewas obtained: (S)- {1 [2'=metiyl ' (pyridiri=3' ylrriethoty) quinolW '-, yl]'-pyrroliin 2=yl} =, niethaziolas'an=tht ellodso'lid: ISP: iiisss-: ctrii; stn/e: v50: 5w (M+iclulateclfor ° 'Examle 98 : :,, In analo'to'exam lev,. o r, eaction., o, f (S = (2 h dro, ethyl-yr'rolid'rn-1 lj-,. 2- methyl-quiriolin 7 0l, roduct tif ecariple , ytli5 chlororriethyl-pyiydmi2-cabomtrile ,..,.., ,,. . _.,., : A ,..... ., :., there was obtained : (S)-5-t4- (2-hydr6xymetRyl-pyrrolidin-l-yl)-2-methyl-qui yloxymethyl]-pyridme. 2. arom yloXyrneth : pl] =jiidie 2.-arb, onitrleas an, lrght yellow soliti. ISP'massseetrurri,'. rnle : yloxyni'ftl m-/e !

Exampie :'99 ; a) Amixture. pf3. 1 gpf (lp9'mmpl). of7 ;-bertz .,. , j t.. k d..'p G ; i :, a_y.',. n ; t i. r a",'a ;. quinoline and 1 l, ml (218 mol rolidine was heated at 80°C (ol, bath tem rerature) under an argo ; n åtmosphëre'f&'6'h.,-Th^ê'reaCtiont ixtur-ei wàs.. concentrated in vacuo, the p, y, eiqe, ate .... . ..,...,. residue : : takeri'u'in meth''lene chlorlde, . which vas was'lied witli'wCer. : saturatecivNaCl °. solution and'then dried'overmagnesium sulphate. The solvent was removed. m vacuo, the residue purifiedby nashchrdmatography on silica gel with CHCl/MeOH (100 : 0 to 90 : 10 over 1 h) as eluent. Combination of the purified fractions and concentration. 1.7g (46. 2%) 0fthe7-benzyloxy-6-uuoro-2-methyi-4-pyrrolidm-l-yl-quinbline asa . :,, 337)..-'\Y." ;. : ;'''',.' "'..."--"-'.''''. .. 337)....'r ,..',,,,. .....",, .. y, ,. ;... T . r C' Preparation : af the startng mater. ial _ > r b) A söl : uf-oSof, 50, g tO 3, 4t rko. +y9, ; ~thNlgeiiea , chlEdè ht « et 3 : go 4 efZtt-te, nbu} pin mlòf i^S le'k'de'p'ing^tht,, aAiEorí^sòlutib ê^>eenr ars :- md d, dfid"- ./// , g ./,,. ;.. w i////z.. _ : 3 1) and discarded. Th, coriabin-ed aqueops, layers- were malde as'ic with solid,, NaHC03, saturate'd-vii NaC eitrated.'5--, t*lmes'.'With, '. 5'1 o. 'eter' an ce : y, . n . A I..., ; y... L.. .'_,., T.,... A a-rrio. nm. aodide cooled. . SC : an thetreaed : nve. a' eW ods'b25m. u-e. w : 'm, ,. d p s th 60 .. . r w : : ,,, e,. -,.. : : ,. a ;.. . i,... ,,. ; i.. '-,,. .. ; le :, . , c , 9 y :. ari me l) -, w6ie, treate*duner"''a'r"gon .. ",. ...... y ..-^ qT _., : t : i,,, _', (..,. water (6l) ; WYthstirringthe'layers-wejeseparS mehylenecMerideeaehS ',. yvater (61) ;'with stirring, tlie ayers wereseparated, the waCer ayer tmce. : extrace.. with .,,.... , eoncentted , :.. (each 21) and discarded The combmed aqueouslayers were made basic with solid : c) 79 g (0.62 ni6l) \of4-fIubT6-3hydrbxy'anuinein argon NaHCO3, saturated with NåCi, extracted'-Stirnès'wih, 2^. 5"1 of ethèr ánd. t^wi^cè with I. 5 1 oft ...."''..'-'. fj'gf} '.. lcOEt : The : c, Qrrtbned or, gamc'ayers ere tred over ma nesmm ; sul ate and ;..... ,",.- :" g... cone t ated<'-. u xo,. ive43,..., '. 87. .. : o : uT {'.''..'r','''tur' !'-'' !''/% ci.'t'Kf''*. <''-. ?'. *-. 'M' ; h dropwise while keeping the temperature of the reaction solution between RT and 30°G. _...,...... ;, 5, w', ea 'c) 79' (0 62 inol) of uaro 3. li dro =ariiline m rD. IVIF"CI 3; 1) were. treated under ar on portionwxse over arper'iod. of 15 imnutes with°, 76 7 g (0 68 mo1) ofpotassmm t-butylate p s 5 j s j ; j"t {i} 0 i r over. magn-e"siu'r"n's"'-faie an t e-so ventremyei in 'washed -a66-. Tlf" sidue i. fi" db a vi. i : t,"- ! ;'."i c-°"_' :. y -^e"E y-. : _. r." :"i 1, : . r : ; ? i lo. T. _', w ft, y : I,. , ^" . W ta, dropvise while keepng ; tie temperature of te reaction'solutionbetween RT'and 30°C : r, {5,-Xi,-ir ; a « *ì e^g ; pef5^ ; @ l vi5 !. 5< , s3,., d. t, hrl, ^g, e,. t, l., S,,, l-.), >a*dO'ri, ed, over magr, lesiurni sulfa, te an< : t the solye, nt^remoyied in' "t h t ì > t S W 4 w t i i A rP ? 5 i * "* v Xg ^ 3 ; ; 2 v A ; i ; $ ì < i w then eXtracted 3-fol., mth ether, . about. 31 each) Th corbine. orgariic layers were.: wash. edythbrye; (, 1.51; and crid, over mainesiu'? v'sulfateanctliesorventremoVeclin vacuo. The residue was purified by chromatography over ; a short silica gel column with

methylehecMorideas'eluent. Combination of mepurin vacuo gave 92 : 7 g (68. 6%) of the-desired 3-benzyloxy-4-nuoro-phenylamihe as light yellow crystalline solid. ISP mass spectrum, m/e ;, 218 ; 2 (M+lcal : ; _ :.....,.,,.. : c) 92. 7' g (0. 43 mol) of 3-Behzyloxy-4=flnorophenylamine/5 (0. 45 ! m6iy of ethyl acetoacefate'and 0. 81 g (4minol) of'p-t acid mbhbHyd'ratein 370'inl of 7, ; t. <, : y. 'cyclohexarievVre lieateclaLf refftu for 3'h intlievpreserice-of aviiaferseparator furinel. The reaction'mixture Wis,"66 t 6, A-T-'I e'aqire6i ! §'NA CO's i : on (0, 51) were added, the layers were separated and' with ., ; ;-. AcOEt (0. 3 1). The combined organic layers were dried over magnesium sulfate and ....-,.. ; _., , ,,., e, :... concentrated in vacuo to iye I40 I00% of the desired 3 3-ben 0 4-fluoro-. s g ) . ZY xY.. phenylamino)-but-2-enpic acid ethyi. ester as yellow-orange crystalline solid, Melting pzylo7,, 4-fluoro- p0lrit : 79°C 80°C, e S. ç.., 1'L I H 8 j i. t ^ ;/ ; t I 1 A f. point: ester in Dowtherm A (220 in) weie added=drowise under argon to 400 ml ofDowtherm i .,'.. , W.. ; .", a, s w. t°' t'.". e, : I.."-f il ; 1, ... A,-.. i- (,.. ; ; f; y. 3..'-,.--. . t_,'Yi, (bih i kt-aiia n-hexdne was a de wiil iy a . u .,, f, ,,. u 7'.'i ; . , _w tA q y... y , ,., % . v ' : w :-.. 7 _.,. . a. ; .. : , ' =. l. d,'. tf ! f , ? , m° :. c x :.. i i, 3, :. . .". ;' ; ? 1T ;'i , aa., 250°C liath tempeiattre,, cooled to RT and n hexanewas addecl. with strryg wlere'by a li ht brown solid. forme that was cQllected. b filtraton a, nd washec yyith 4 xiines yth n-. hexane : The. solid was then tmturated with ether, collectecl ; by suction, washecl 3-fimes with "-y tration and washe.., ether and then dried in : athigh vacuum, to giye'33. 9g, e 6r,-coll6cte-, by, s,,,.. 6 m Is with Ruoro-2-methyl-lH-qumvlinA-one as alightbrow., solid. ISPmass. spectru'm, mSe 284. 1 (M+l''calGulated'i7FN (M+l. calcuated. for. lHi; FN02:. 284). 0...." e) 67-. 8"g, (0i33'9'rnol) of. 7-benzyXox-6-fluoro-2-meiyl-lH-quinolin-4-one. in 220ml (2. 39 ..-.. ', _. v,.,.. . y.. m _e "..''1......, v. IL .,. n.. .,.. 1.. . i.... c !. : ... mol) of POCI7 ? were heated at refliux for 90,. minutes. The reaction mixture was cooled to "'-w"as'ea'b i E, ,. ,. ."", a-', . ; a i, :., Iu. a_,,- (.', c, j C., RT and thersolvent was removed'in vacuo The residue was partitionedbetween. ice vater (15; 1) : and methy,. erechloride (1,; 1), nd25, Q. ml ocncenGratd; amnionxa, yyereadded RT and the solvent was removed in vacuo. The residue was partitioned between ice water .. Y. :. g. J.. . q 'P Y r,, P. w aqueous layerstme°ecxedmtlmefhylene, chlorue : (each 500 ; m1,,, e cqinbined : flUÓ, OF er or anic'la eis wereyashecl mt'h ; fixlne ; driedove-r-riZa nesiurn ; sujfae : a.' d tlieri, !-,. ; .. Y,.,. g , : j,,. , !'... " t. r,"yf s_i. ; w y.., y_, t : v ,.,, -"'ti-. 4 : y !.. :-i, .. I , . i aqueous layer., twit,-extrac ! p I I, T organic, l ffuoro'-2-meth rl-uinoline as axi : off wte solid IeIy, ; oyt 1 ; 10°C ; 111°C"., ; . Y q : ..-.. P . , . '. -..,. ... . _. ., ... _.... ..." o... ..., :.,..,. ,'. e.. v>.. ^".,...... n..... ;...... . _.. _.... :.,, ., :' :',. _-n..,

Example JOO ,.-y : t- : ! A solution of 1. 5,. g, (4 5mxnol) , of 7 benz'y. loxy, 6-fluoro-.'2 methyl. 4-py, rrolidml,-yl,, : ,. :, ... quinoline, prpduct; of xample9; 9,, lissolved; in 40, m1 o, fMeO. H: wastreated; watl. 0: 3Z5: g of palladitirri'on, chaicaal (1 : 0%). a ; rid then liydrogeriated at. : RT for'I : S° : h until-HPLG- : analysis indicated the compledon dft&reactioh. Th Sitered oH and the solution was concentrated m yacuo. The residue was tritu : rated with AcOEt, coRected by filtration, and cori6entrate m y'T-hO'regia7 driecl a g, o, g. . '. .. )... Y, =PYr' y. utirft to yr C4H5FNQ : 247). .. ...., .. u, ..'t.,, ... f^,...,..... N .,..'. aYtl J [j : .,..., ;. E le : 101, . c j : L- y : .. 7F M. s '. 'iGi t ! J .. i : C'', ir v i7 r 7. . y . ; a. , r-Cf, a t 1 gpii p f. j :,) Ie,, Q., with44-br. omomet4yl,-benzonitrile "''"""'""'Example'lb2""""""""'' ' ,. _ ;,.. ..., , :,. t_^I', ; ,,., : _ zY, , z : ;. jsA,. , ..' r Ss. v. : Mc x, pEy : , u ; : o,, , t j, !. mf.. t ?.,. ; r,.., : ;,.. 7. , . L. : ;, : a.-... hreb _t e. ro ,, uct, w s. isolate as ree,; base, 4, (f Yflwor. Q, -meth.,',-4-rezlid-. 1. v1., (7uinolin-, 7,- loy^ (eth, 1).. rbenz, oytrle as a: r. o£f white_solid, IS, P, mass,, sj', ectrum m/e: 362.2 (M+1 ca. lculated for. CiHoFN30r362).: . ta . In analogy to example 6 theie yvsprepareci: on reaction of 6-ffuoro'-2-methyl 4=y. , pyrrolidin-l-yl-quin61in-7rol, product ; oxajnplQQ, th : 3- hydrbcMoridewh. erebyth : prdut : ,.,.. ., : _ , : a'. ,.'.. :.-.,. ;- {. ' ;.. :' . . . ;'" In analogy tq example 6 there was prepared : on reaction bf6-nuoro-2-methyl-4- pyrrolidim-1-yl=quinolm=7 ol ; : prod'uct of examle ; 100, vith 3=chloromethyl 2-ffuoro- pyridine hydrochloride Whereby the product as isolated as free base, 6-uuoro-7- (2- nuoro-pyridin-lmethox)-2-met mass'spectrum ; m36 : . F ; :. i.',, _ ; ;,, ;. , e - _.'l :.' r,. 3 :. C e"t r ;, massspectrum ; iii/. 35 : 4 (M+T'alcultedfo ao-Ii'9FZN30 : 356) : ... _,., Y... .,...

Example 104 in analogy . : :.'.... 1n anatogy.. to ;. exampie, 6 : _thr was prepard. , a : tz ieactip, ri"of 6-uoxo=2 ; rriethpl=4= . ; : , : = pyrrolidm-l-yl-quinplin-7-ol, product of example 10, 0, with 2-chlprp-3-chlorpmethyl-, ., : : _ ;.. : . ;,.,,, p,. _ 's, pyridine hydrochlomde. whereby, the product° was isolated as free base, , 7 (2-chloro-...,. pyridin-3-ylmethoxy)-6-nuoro-2-methyl-4-pyrrolidin-i-yl-quin oline as. a light brown solid. yr4in-3-y, r p 0'lid. I ''.)'... :'... .'-...''.-f °".'.-""---77*'... '..''.'--'''' In analoj ; to e, am, pie, 6 therejw, as prepared ò, n rea, ction. o, f, i6-, f'öro-, 2,','me-4'. ;", pyrrolidin-l-yl-quinolih-7-ol, prbduct of example ,, v-Exaniple : 105 ;,.-, °. <..,,,., ;, ;, _.. :, _ In analogy. to exairiple 6 there, wa's, pxepared :. on xeaction. of 6 ffuoro 2=methyl 4'' _ par pyrrolidin-1-yl-quinolin=7 ol ; : proauct of exainpl 100, v. th 3', chlorornetiyl-2 rnetliyl- . :.. : pyridine hydrochloride whereby the product was isolated as free base, 6-iluoro-2'-methyl- 7 (2=methyl-'pyridin y r4 pyrxo i go p . '.. . .. e ; fo C21H22F3, 35. )...,' ; . , ...,. t, :,.. .,.,. ;. c, u.....,.... _...- ,.'1 c., _ ; r , . ,. 55, ; v. , i.. , Exainle106 _.. _'.. . u.... _... ,' ; ; i r t r,. ., a r.. s ;, S' In analogyto example 6,. there was prepared : on i. eactM pyrrolidin-1-yl-quinolin-7-ol,. produet of example 100, mth 3-chloromethyl benzonitrile whereby the product was isolated as free base, 3- fluoro-2-methyl-4-pyrrolidin-1-yl-,. qu i ii o I i ii-7--yl 6x y-m-h-'I e : ff h P-1h. is's--sp M/ In ,,, F j _, pyrrolidin wAt iyl-qu, i.. n, oli ;. D7, iC ipr. o,-. du ; +00. 0, 9, 2-bromö, nieffiiyi : benzXni. trile zu pyrrolidin-l.-yl-quinpli ; n- -. t, r'. w _W. _., a. _...... : ;''. _ z ; td n, '= !'t4, ., ;' z. ..,. a. l, : .. Y ;, : v 'i t. : _.. tk. , % Ylllr,'' ! y. _ ;, u... rn : y 1 i ; ks t Y : ,..,. ed x :.,.. &r r.. j (. y... . ' ! °" S. Y.... °r : y' 1 :.. .. r. f ..' ; -y... !-. v,-=...- ,,.,. r, Examle I07 ..,.,,. In analogy to'exairip2e 6'there wa5 prepared., on reactioriv, of' fluort 2-metHyl 4,. _ rolidm-X, - 1 u, xnoliri='7 0,,, rodtc, t of exa. zix Te 00, ivith 2 . bromoineth 1'benzoni. trile whereby the product was. isolated as. &ee base, 2- (6-fluprp2-methyl<-4-pyrrplidin-l-yl- quinolin-7-yloxyneyl). b ISP. Tnas's sp'ectrum,- :'m/e : ;, : 36Z2 (Ml-calcul ! ateddrIoFQ :. S62

Éxarn^plë-108' In analogy to example 6 ther. e was prepared : On reaction of 6-fluoro-2-methyl-4-, pyrrolidin-l-yl-qumolin-7-olproductofexam 0 7-clo 1io lme ; tho-, 6-fluoro-2 meh l-4-- roiclin- : 1-, 1 uinoline.. h, drochlomde : as a yenow. soRd. ISPmassspectrum, : m/e :. 30. 3' (Mlcculatedibr. Ci8H2i ellow. solid : ISP m'ss s n'ectrum m/e, 3413'-1'vlculated for C H. FN O : 301. ,.. : zs Zi a) In. analogy to.. examplc 6 tb. ere was prepared :'on ; r'' pyrrolidin"l-yl-quin6lin-7-ol,. p]'6duct of example 100, with ; 5-chloromethyl-pyridme-2-.. carbonitrile, whereby the prpduct was isolate as, free base, 5- (6-flu, oro-2-methyl-4-. ; pyrrolidin-l-yI-quiriolin-7-yloxymethyl)-pyiidime-2=carboiii frile as light grey soid. ISP as_',.-.., mass 5peirn ; rn/e :'36g : 2 {lvf1'culatd or C2iH9FN40. 33v) : P--.'.' ,... 9, 5, ,-, rf.. t , ^, I t . ,- :. -. . y' : : ., a. . . ;, s... ,. :".. FIO) 4, 0 , l ? .'n. _, ¢, a t. 1 ;, . ;. 4 . : r. ,'1'C.. L_e Y'' !, x.. : : r'_. A suspension or'3. 2. g, (9. 5 mmoI) 6f (R-l- (7-benzyloxy-2-me ) (.) (,. Y XY Y,. q.. Y - . 'e ;. .,.. ct was treated at RT under nitrogen with 1 : 42 g (12. 4. mmol) of potassium tert-butpxide. The suspension was stirred for 20. minutes afiRTtheri0, 72 iriIin : vmQ1) ofinethyl. ibIidiier°added : ter25=miriutes of irilt6s.-wer e OJl'44ml2. 28'm61bf'melodide .,. a.. 'L,. ; , ; !'. !-r.. -4/-, 0.1: 44' inl : 2'8 rn"bl) of rliethl nocl. ide {l: t? znlnrztes TCer) ftr criinpletioii-offlireaction. g6i'd's"s"I'U-f,.-'te-fi-lbutb er--e) d-dd,"f6116wedb the aqueous layer. once extracted witit AcO the combined organic layers washed with .,..,,., . , F.,.. .,,.'ti.. . n.., ; :, , ^. i. k ,.. t,. ar. _ :,. tJ Yro."...', , ,, , t,. t . vacuo and tieresclue artitioned bet-tven ; water and AcCEt-Te layei=s were searated .. : b ; s. _ k.. ;.. 1.. m A.. :, :, _. i r ! _ .. .. . . : r.. .., :.,. sos.,... _ filie a ueous la er orice eXtraced with. tlcOt tlze cornbiried or amc la=ers. vashed'vith x . : y . ;. . : d a v A t r , _.'-° g,. 3. ., s : , : 3 vacu o an"e''r^ e's', f if&' ; iftiti o n e Et-'T I'yers d a. g _ ,, Y , s r, f. -, : t . t.,. \, y. t f (.,". : t b .. _ d'. . (R)'-7-benzyloxy-4- (3-methoxy-pyrrolidiH. l as ah orahge viscous e,, '., va 3, 33 : g., (94w :. :. A. ., ....., k. , t., (,',./'.,.... v. y°. 4n, .. ,," i,,. : t : ^,, ..... ,,,., Inanalogy-toexa. Bpl'MO&eEe. aspEep ,'. ;.'',,. -, ; : _ vl_. ....,, ;. peu ....,...,..., o,........,. -. : ty : ,, r. n-v^, , :.. . a. STNgE f t, , ,'. ..... 7. i. : sE. :, x., ijtYo : °f -.. y.. : x<', i,.' _ 'e-r''-_. z ; n, , ...-, . =.. y. ; . °°-.. 3-xariyle i'II'r.-r... :.. *.. =, __.., :. . .. . r,., : , a,.. c __rY : t.. a , 1....., r. =., ;.. ;,. F., a. n In arillo. Atoex. rripe. OLfihre.. , vasa. ze ard'on: ractyn; ofp (S).-, _ (7fi, be aa. ; ; r. meth', 1*. uino., ln ;:. 1.) y: rrolidiri. 3 0l: xoduct of. exam' le 85r m; th. 2 br m et;', 1: ieth 1

ether, (S)-7-benzyloxy-4-3- (2ethoxyetho orange viscbusQu.'ISBmass ; spectmm)-m/. e : 393 ; n S. 1" tr v nr . .-: EXain: ple 112 In analogy tb'example 110 there was prepared : on reaction of (S)-l- (7-t) enzyldxy-2- metliyl-quinolin y j pyr xdin o, pro uct f. e ample 8,'viithwme hyl iodide ; () 7- ben2yloxy-4- (3-metho ; -pyrrolidml-yl)-2-met oil. ISP , ma'ss'spectrum ; iri/e. 3. 49 : 3 (IYI+T alculated. for Cz2H2¢N202. 349),.'. :'.. _... _ Examle 113 - ns='S 3> . r r 1 0.- d v'. o xr Iii analogy to, exafnpl'l, 1"6,-, it',-w. as,,. prepare In analogy to exsmple'T'l methyluih6lin-4-yl)-pyrrblidin-3-pl, product 01 example 85, with cycldpropyi bromide, (S) =7=benzyloxy-4- (3 cyc'I'opropylriiethoyi ; yr, ralidinr. 1=yl). 2-niethyl=. quirioline as an 2 oliii as an . i.., !.. : 3 i, _ ;, t I t..... .........,. t ; '...,..... ..,,."_ u =. 13. . . ., _ ; _. " ; p w.-7". .,.,'t .., _. . , i :. t. . ,'o'Y, lt _'... . ..... . t3,"..,..., . 7. " isi2b2 : o , t, . y.... . : ;. Ss,'t ;, fi,, i.... S :. l.,.,"t,.. F _. 5 : .'wi__. sl.. ' :-'t, ty. r, ...,.. 5.., k : s'i> . siam In analogy to example 110 there was prepared : on reaction of (S)-l- (7-benzyloxy-2- memyl-quinolm-4-yl)-pyrrolidin-3-ol, product of example 85, åc'idB ; 4 LA"e methó-propoxi)-pAlgi^ -meffioxy-. prop-ox) r-pyrro 1 in- ,- e. v f. 'v7.. J., M : . , r... 7., _i. .. .-,. u.. : j'.. .., i. . ", p. . ni. »-. ..... ín anâlogy'to example ^li'Ö Wérewås piråred òn'r'èà-cdõr'of (S)-i'-(74r 2- . t : t_, 1 ; j, y.,-. :.. J t ...'t. . J. s TJ r, ; i . ii ,'9'6.'4,, u... '.-, calculated'foi C25IgON203 40',, ...... .. _ _.. z .. _.. _.,.,.., . _ w.... _., _ ... : « _, G : rc,, _'a7 ! .. _aj : :,.. : :.. _ r, : .,.,.... _" ? (. 1 :.. _ wr_... .. t.,. sy" ; i'...,. ; 3.. ; r '',, :.,. L-".. , t. ; ft ; ?'Q_., _'_S. _°8 . t f'"'_ _ ;.. z : t ; f. I , . .,.. tF" ! _...,. .., > >r -,,... ,.. _., : ;.. . i..., a . E' ;...,. .. 11 ; _ '"_- !. ; : ;.. Example 1 T 5 In analo'toexarn. Te 110°t'ierevvas °re arecl on reactiori of (S)-1= (7=ben'o '=2=' gY p P p ZY Y methyl-uinolm-'4-y)-.'rolidn-3=oI, roduct o£ exam le 85,, 2, = (2 broino=etlio')-' tetrahydro-pyran, 7 ;-bezyloxy-2=riehyl 4 : = {. (3S),. =, [2= (tefraliydro-pyuan-2ryloy)-. tet h'-rii xy) pyi'rol, y}'-. q llow ms s. il.. IS,, p m, mle :, 3, 63. 4 ...., i .., . ;. r,.., ;'..". , .. 4 : t.. ait lys

Example. 116 -: : In analogy to ample2) ; on, hydrogenatipn of. (S)-7 a- pyrrolidm-l-yl]-2-me&ylrquin : oline, produce in, MeOH, there was obtained : ; (S)-4- [3- (2-methoxy-ethoxy) qumolin-7-ol as a yeUpwoIid. ISPmasspeGtrumrm 303. 4 (M+l calculated for-, pec ru C171 ; 3 :'303). In analo to exani Ie 2, om h ; clro enayon o"f (S)., 7=ben lo,-4 3-metho r_olidin- l-yl)-2-methyl-quinolinprQduct ; pfexanpl, e ; l . 1- 1 .-. 2-irieth 1-. uinoline roduct o£ exam l. e ll;, yva. thPd on c, arc. oal 0°/. 0) W IvI, eO, H, there i'vas, olitained. : : (S). 4= (3 mehopy-pyrrblidin-l-yl)-2=rizethyl-quinolW 7-0l as : aP ,, : ; : - ;- ;, . ellovsoTrcl: ISFrriass s: eruii3-m/e: 59: , IVI-. 1 clc: ilated foi=C Hr: N O: r25:- "n"" !,. ;"". ; 3,";".,, e Ini.,..,. ty .. 'T,. 1't..., r. _.... r.,...'1 s 1. x.... :.' ; u. l.. ed,"t 4 , u :., ; . is.. aftt-. i. t.', G :,',, ts. y ;-. yi , z :. w I '"'', _. r q'-. p u, _" .. (vi r. ; e' f. :. s.., v6 ,, : _. Exame 21 .. In arialo. to exarzn le 2. pn h dzo enaton of (S)-7,:, enzylocy-4 (3<., cyclopzo. pylmethoxy- rolidm 1-yl), =2-inethyl- uinoline ; 4p'r, oduct of eX : mple, 113, tli Pd on :, charcoal. ( 10%) PYr :,, q . ..,,. :-. , :-. -'let QS H2 02-^ 299B, ^.',... ~ À _., % ~se,, ; 2o ;. ! > --. w. , quinolin-7o1 as: ayellow; solid ISP mass pectrum,: m/e: 299.3. 1VI+1 calculated for;,.;. Ciaiz'Ni: 299) . . _..: S Tr-} r 4, 9ij"~. T,'V a 2 thVI- oli d'f P4,, o4"ch rcoal. (109/o) Inanalogyexampl'e prbp6xy)-pyTr6lidin-iy []-2-mfhyl-qm ; 'yF. s-... §, a.. :. _ ... s, yh., s_ ai'a, t> » Lt, C, . :. .. z.. ; : E'i . _3 .. iF.... s,. ...'L_- -' !. - :,'r. . r . , ydt.., Exanile 119 299,,, y ., ;, w :...... 8-22 2. In arialogy : to'exampl"e 2 ; an . yelrogeiiatron of (S-t berzploXy=4- [3'= (3'-metlioxy- °Y ; e,, _,, on', yd t i'opoxy) pyrrolidin 1-yl] 2 metliyl=gu naline product. f eXanpTe=114 ; mth Pdon charcoal, 1t% in IvIeOH, there » was obairied. S =. 4 3= ;-3=meth-. ro , o.'-'. rolidin- ... ,)...,,.. w.. (.).,. [. ( :.... ' : p, p. XY) _. ? 'x : ° . =r'x r l.-l =2=iefli 1 uinolW-7=al'. as.. e :'o sold : ISP rnass s''ctfurn rrri-e :-3F7 v TT+1 ' : ? ;,, wu a ". _y . z. ; : (.,. i. l'.. -_, i.. W, t.'....... ., y. p -... ; t, ., ! ; ^,.. , :, _, ,. ° . _ Examle 120'. In ainalogy to example 2;: on fiydrogemation of 7=tiemzyloXy 2=methyl=4 { (3S) =3 [2= (teahy<egpyran2ß@'-êthoppróii-iyl}->qb+bAuctFofî4l ell5 . Ir.... v.,.., n,... a.. t^ra m.. u...,... . v...,-.,. n...., ". 4In...

a with Pd on charcoal ('10% iBLMeOH, & was obtained : 2-'methyl-4- { (3S)-3- [2- (tetrahydjo-pyTan-2-yloxy)-ethpxy] Yp as a yellow solid. ISP mass spectrum, mie : 373. 4. 3 (M+1. calc. ulated for C21. H2$N204 373)..,. .-,- Examgle. 121 'e'xa" . ^........ ; ". t. i . i 1 _, iff . _ ......... ,.,. f ; .-,,,, , :" a Examle 121 Ima'nalogy'vo eXaiiZple 6'on. reactibnif (S') °= 4- [3v= (: =metlioXy=ethoxy) . pyrrolidiri=1 yl]''=2- methyl-quyolin=7-. ol, productof eXample 116, vnth 4-bromoxiethyl, benzonitxle there' was obtained (S). 4 {4- [3 (Z-inethory etliory) pyrrolidin 1 yl] 2 methyl-qumolin-7-, ., k.,..., s. ; : ;. A.,,.. :. ; y.,., a : :.., ydAoride as, a. light, yeRow'solid. ISP, ri5', -. pOIum, m/e : . !-. , 1., . .. .,. y 9"9.. 7. 7, ,.. v, A., 4, 18. 4 (M+lcalculated for C25H27N3O3 4, 1. 4), ;. ;. ; : ' (. . tY." ; uYc"n d... :., d. aif, ! _.. , i'r,...... 4 3a 14.... ;'r'. u t. ) 'tw.... :. f, iTi . t t .,. i. " iTIh. 17YI,-. 2 ih6ihyl'- .. k _ S t .. y . s t a: i Example, 1; 22,' n j ,;; r In analogy to. example 6, on reaction of- (S 4-3-metHoxy-p ,,,,,, :.,, ; quinolm 7-0l, prouctof example 117, m. th k bromomethylbenzoriitxle there was T c : ; ; a t'. r ; c al c ü l áted fió r C 2 3 H 2 3 N 3 0 e 3 7 4}] A ; A ;,, À, !. t s J I A.. X, I *. e... 2 ... t J Ä v L 1 S T ;.,'> i * ?,.} ; S i J ;. r X A. . Y.., g.,. Y , ?... . eq'ûInolih'ii'-'ol, pio''dùct^dé, xa+wwm+be zonitri i^ ere :. , t.,. ', °i,'. r ," : a n',' : t3.. y, b '. _. ,.. E. n,.. ;,. ;,.'', u u...,...,,' P. y 0 1 I t ! - I, . '.,.,. _..-i t.. .,.",, 15 1. , i :. ,'.: ExamIe 123 Inriialog. y,'oyexample 6; on reactioriof (. S) Y 4 (3; =cycopropjlrriethoxy pyrrolidiii, =Al=yl)'=2- ine'tli 1 iiiiioln="7'-01;:. oduct'o, eXain e l, r& vith 4 tl'ioriioznetli'l, benzonitrile, there was obtained : (S)-4- [4- (3-cyclQpropylmethoxy-pyrrplidinl-yl)-2-methyl-quinoli in a... fr . 5, :" i f°.''i-l ,. yloxymefhyt']-b'enzojliile'hydro'cMbriue P : whitc"solid."IS'p'mass spectrum m/e : ..-, (. I.... _.,.. p 2 -I 'L 1... f........ 414 : 4 (M+lcal'culated fo ZI IT302t 41 aF'',, 3xt. : a f a. x. r.... r,. , z) "Y. ! 7. ft 1. a . J 1 s 1 ; q a..-. .,. .., T.. i . p. 4$, r v... u,.. . 4r t -y"1., . _r'°', k i t < f , Exam, le I24;. w .'..... J, ! _."E- ;.. 1. _.' i ; i', In anaiõgyto ekti. pi-e : ;, 6,, ç, onirëõn^^of ; :'(Sg, 4t, (3 kprópòW)-IVl'9 ; i]- 2-methyl-quinolih7-'61,; pro 2-iiiethyl= ; qurribliii' ol ; ; product of eXaxnpl'e ; 119, wth. 4-bromomethyl benzonitrile there wasobtamed :', (. S)-- {4r [3- (3-methoxy-pr6po yl6xym'eyl}-b'enzom lo T -etli 1} li'eizorrile hydochloride asan off=whit, esolid :-. SPYiiasses ectum ;, rrile : -- YYm Y.,,.... :... 1' 432" (MMated. for

Example 125 In°' ° i gy gY,,, p ,..., Y,., {, (,, ,. [.., Y. e.. i ? yr.. : >>. .-y in m16 12c with 4- bromomethyl benzonitrile, and subsequent. cleavage of the THP ether protecting group vhereby the product'was isolatecl as-free base,, there was otamed: (S-4 4 [3= (2=' le p, was s 'white;,. ,", ; ;"",", ^ ;., am e1,,,,. b, ; j ; ;-; ? ; ; < vhite yellovsolid.'TSPmass spectrurii ; m/e : 405 3v' (M+1 CICLlI3teC°fOr'Cz4H25N33 :. 3. , .. ^ "s4 u,. , y, r ,.. r .. li.'' , ;'. . ,. u.... 1 .., _°-y s ..., . ty'a,... t. : . '.,, , -, t.,. ml.. .. F 4 j .'r., s.., t,, r.', t. i. :, 1 .. :... r t. ''Examile 126, ,. In analogy fo exaiTiple 99;'onzzeactiori o-f 7 henzploXy-=cl, oro-5=luoro-2-riiethyl-. ;. _:. ^ quinoline; vifhan eXCes Qf, (S)-- (: hydzoxyriietliyl) pyrrolidrne" (2; 5niole-eqmvalents°un 1-riieth -, 2- oltctcixsolen-a. ; 100 :, Cfilzer'vas obtarred...,. . _ ; y,. ben Ici. 6'°. in I o ors quin6lin'e*'Afth- Wfif 9. 1,00.0, C, In a'rialo& to 6xaM''pl'"'1"00'*","ldi6g6iiati6n-, bf, (S)- e., n, z, '. j", iT , i. 1'. ' _ -c I : . m'âsi s'pêctrumjNrtnjteii'2> ; ated ftir C2H23a.. 3 (f ; __... .. d :.. 'ti. r... ! t ...,. r :.. i. . . . Examle 127 Tn arialogy to exariiple 100; on hydrogenation. of (S)- [1 (7=benzyloxy 6'-fluoio 2 nriethyl- quinolin-4-yl)-pyrrplidin-2-yl]-methahplp t,.., ; P, _ a o' (10% in MeOH, tliere vas obtained' (S)-6=ffuoro-4 (2=hydroymetliyl pyivrolmliri-'1-yl) = 2m'ethyquinbEn' ;, s.. ,- ;. .. ;"'Y'''-.... h-i--b S'6'i", '' -c r -, d .. : ''. r.' sy. Sv ; , t. t. -r : ;. iT ; j's. 7_> : : 0.-. : . ri, :. :. caltt'afedfor=1HTFa2 : i9y.. . rs... f. ;... : w_, ; ..., aw.. _... _,.,. , _. . : 6 fil 'in"an'logy fe 6 eactfon '6io y'roxyme Y 7PYrrO-idi In analogy to'exarriple 6, on reactiori of (S) =6-luoro 4=, (2-hyclroxyriiet. hyl-pyrrolrdm-1- Iyl) 2-rriethyl=qumolin 7 ol, rodict of : exmle 127, with 4. broinomethyl'6enomtrile ; ' _,-. : b--, - ; 7 a : whereby the product was isolate<i as fre base, there w pro'u' (S)-"47 [6-flij-6i gféy ; solid ; Í'S,'^P, i9'riZåirssÄsjp't +WW CA3H22 A Y . Y I. ;. : x Y I., Y : .'s :..,,. , s , 'cl. IP. rnas'ssect'' : _ :.. : for. H : : ;. li lit re-soli, rum n/e 39. M. 1 c ciza. a3 az N"O-'9Z :. . g, g Y. : P a 3 2 )

Example 129 In analogy to example, pnjEeaction. Qf (S) 6-fluo yl)-2-methyl-qumolinr, 7 :,-pj., ! prpduct ; ofexam c, axbonxtril. e, whereb the-, r, odu, ct wa-isolaed a. s. fre : b. ase, tlier. e was. obxained S°,-. 5-. 6- .,,, Y,, I ?.,.. L _. r, r5..,,.. :... :. n z . : :., N _.,.,. ). [ luo, r-4-, (2-hydr : oxymethl p, yrrolidir, 1 yl) -2. ; methyl-qmnolin 7 yaxyethylJ :-. gyridine- Ç22H. 21F sN., 92 s3, 9 >-'"'", a'""-",, ;", &-""","'", ts,'4..'sr ^^'ì''''S3 ; E' .. :, : :.,...-,,. _. C22H21N4, p2 393.) .,.. x.. °'', <. : '.. , ; .,. '''" ;. ;,..,., a. p..,.,. :.,, ,, .,',,,,. , ., , c,.,. ° ..'.',.,'' ; i.. L 7 °..... k'. J : j. _ '.,.., y.....,.,,. -t t"s t,, =, _.. _',. -,. ,..,,... : Exarnle'fi30.,, ...,.," . _..,,-., Ef a) A solution of 1.42 g of, (4. 6 mmol) of 4 (4-chloro-2-methyl-quinolin-7-yloxymethyl)- ., :.'Yt'. iftE, : : benzonitrile-and 1. 11 g, (. 1 ; 2 5 rnmol), of S),. 3=hydroxypyrrolidine m. l- : methyl 2 . ; ... wThe reacdon-rpiir'ra, assç, i, rlgRrt ; a, ted i"nia : high'vááw, r, nX é resid, ue.-,, t, up. i'm-y OR P : yr., r t- MeC) H, ? filtëred ws4, gàsoh : ëd >seqùen7it : Xta^h :-MeC) H ^ân^doêier.'á'rs. d % hen'dried . r.. , : :....,. ,.. ;.. ;- in, th,, y. len fi, d'ied .,.. .....,. Y_, y.....,. ,,..,.. e,...., . _,...... . _ r.",, wu ,. : a,', 1'tl. was e su dried 't,. : r >,., : ;.,., ;-..... ,.,.,. i.. y,. MeOH, fiered oyf°'b. y. siction ; yashedsutseq. tently t MeOIT, amd°et'heiantlfheii dried in a high ive ! . 9 r n _. , o in ahigli vatcurn ; to. give. 1. 45 g- (83 : 86./0) b. f Ch (S') °=4.' : C4- (3-lijciroXy=p. yrroliclin=l=yl)-2_ meth l: uiriolm=7= Io etl 1-benzonitrileias abroyn solid: ISP.'mass: s ectruin m/e: 360. 2. (IvI1Y calculatedfor CZI21N3Q 360. ),,, 3 2. : 36Q. Preparåtionthe star, .. y, 2 t t u : 0. 1 r b A : sol on c is for ! l, h , ; q,.. s.. ... y^,.., ;. , : 70.. 15 " : ^ 7 ' : r. 31. ; t. F... r.. o . t. _.. ,., M i. ; . :... bt." ru.. p> ; ja r, r^,. 6 :. re ^, , 1.... 4r ?. "eH. '°S r. e". r r. t : y e _ d,, s. __. _ t : b-A sol. fiaon _o. f 3 7, 0 5'zno, f7-be o 2 rneth 1 uinoli 4.-0l. roduct of., ex le : c, dissolveci. ir. i 270:,'. of lVIeOI. -as treat d. wath . of] adi7'p n: c ar. aal, , 10% and then. h: dro'renatd. at Tfo: l. h until. IH. pTL., Canal7rsis dicated he-co petio: n of the. reaction The catal. st za; filter. ed off +washed mtla: e0..; and the. soluti. on was, concentated in vacuo The resiue. was txxate ith, ether collected b. filtrati'on aT. 1 d dried in a. h, i¢h; vacuum to gxye 2: 05,, 98: 6% l 2 nieth, lo-. uinoline4 7-diol. as an off vvhite solid. ISP mass spectrum, m/e 176 ., (M+1 calculated for Cloi9N02 : 176)., c) A mixture of 2. 05 g (10 :. 4 mrnol) of, 2-+quinoline-4, 7-diol, 1.72 g (12.5 mmol) of potassium^cårbonatè an : d LI g (rboi) of 4~. (b : romóméthyl)-t'erizoiiitr^ ; lë'in^ ! lOOml of DMFwerstirreat ndeT ! an' until : GpmpTetloh-of the. "... g. p... 1. v.. lt. y"... z i , r, : : reactidnaccrdiri : to... IPT, C ; : anal us :.. , The : rea'nineture s co. oTed to RT ancl'''ouied

into. EtpAc/water. (. 30p ml,/QO ml)., ; The product thatpreci tu suction, washed'withater, cOEt and ether (73%) 6fuzz (4-hydroxy-2--rnethyl-quinLolin-7-yloxymethyl)-benzomtrile as avvhite solid. .'t", fy.'.... TSP mass spectrum, m/e:; 291 4 IvI+l. calcixlafed fo: Ci$H. y4N20.2.. 29°1): v., d) 2.22 g (7.6 mmol) of4-(-4-hydroW-2Ameiiiyl-quinolini-7-yloxy, methyl),-benzonitrile in 14. 2, ml, (151. 7mm. pl)-f'Ppl3. were heated at, urltil. corn'p, letioru, qf,. t, h'e, reacX, ójn.. áccoér, ding ito TLC anaiyjsis, The :, xeaction mixture wa ; s, f unfiil : coriipletion of, the. reacrio, n,. aec, ordu to. TLC analysis'he : reaction mixturewas.. _ cooled to RT arid the solvent was, removed in: vacuo: Tlie residue, was, takeri; u. p: in ice water and stirred\&) p-. 15, niin. uts ;. ThpHas adjusted tp values between pH 910 i _,. p.. u.... p... wl.... concentrated NHQH'anstirTijig was Gpntinuedipr 2h. The brown-solid ; which-'' Vent.,. as, em, precipitated was filtered ofPby suction ;'washed with'water and subsequently dried n a . Cs... _ o.., j t9 r,"k- f=.. . jl. S Ty.'r.. s'.. c. : y : e : i. ,,' .-." '. r'% '.. E ;', ?-t MU. . J.'drie % .'v s' «' . high vacuum. Thi's gave2. 8 g (Y2fl0%) °' oh-'' (4-=chlo'ro 2-miethy=quinoiri=7=yoxyineyl)- benzonitrile asayellow solid. ISP mass spectrum, m/e 209 (Jyt+1 calculated fbr 4 ... t. _t u : : 4'. : f 1.,, tsz. :. t. i. : jzi z.' s ''u r aGbf. T'x b.,', at A. .'. C7iitisiC .. a". iF ? T ;. ;, t7 : ;.,.. Cl.gH13C1N20 309) ter an _, :' ? w.', _.., : 2...., >. : sy..., t ! _... _ _i. _,. ,,, s t' ;. ...,. a. ,.. .,,-. ; : a. , ;. y. , '- ... if : x '"Ef, . v7,.., ..... . T. j : =,.,..,... benzbnitrHe a&a brown} 'phd.. ISP inass sp. eetruni, e : 3. 6p. .,. clpulated r', C, sHl3ClN20 : 309)... amp e- si s 9. : ; a i ; ; S, _, r. Z O ; S Ä i A _ f i, _ Z : : S r, v í _ L ; i 7 v \ ; v ".,..., _ .. ,,. In :'analo ;, ti arri. le_ : 13 (2. on, : eactori, of, 4. ; (4 c'o. ro-, 2L. met, 1-. uznl. 7_. l0 ; -4. . _et, h,. ) _ 3'P.. ., _ s Y. (23 :'358) np' ., P.... y... P-a....) . : a)... Y ;. ;. x3'PYx'..-.,,. :. r :.. :.... s btained. R ;.-. .. 3 h, cr rolidin. 1_ ; I 2 riieth. 1- n. i 7-. . o eth-1 . _ 23KE2 i i'3#5 « 7 ga r +-7 ; * 7* i j7 ; q 7i-4t'. ;'k. t ; Zt r r" e ~* 7 ; i 9 f ec 3 4 7 t . t, s : :.. _....,.,,.,. s, J .. x e _, _. _ ; z<.. oel,. F,.. : .. : ... r : : W !'.. zc. _, tc'°.... .'_La :... .. ."., a' l' "r.. 6 t ^ r r , t CzuIziN i 365, 'i y', r. : : _ . x ; :..... aC. , , i i., .. t ; .'' : t. 'uL. '. ... 2. :-.. l....,, s. iu- . ('.. : 1v S.. ^ 6/ fi. S , l. : yy 5r., i. :--s 7a : : a, ? . i> , a z. :, ' : rg s. _,.. _.. rri nalogy to examle 130; on ieaction of 4'- (4=ch'oro Y2=inethyl-'quW olm=7=yloymetliyl)- b: enaoiiitrie v'roa. uct o e ax le. 30. c1:-:: mth.. R Sa 2 -irieth l i-olicliie there w'sv obtamed. (RSy-4- [2: rneEly1-4=2-rnethyl pyi'rolidin 1. yl) -quiriolin=7: =yloXymethyl] =. benzonitzileaabeigevsolid TS? inass-: specruiri,-=m/. es3S8: (M.-calelated"fo:, _, - .:.'° 'd y pyrrp,, i (. i ere, kvq 2-'iii th 1- 7"' 4i e, y-, pyr.-yox. y ion P. 5 p :) ) Y Y. PYr ... f. .. xv4'''p. yx, I.-.).."1c.'', . .." ,.'<.. .... .,.,.. S"'. _.., t. t. v. , . ., !......

was obtained : (S)-4- [4- (2-hydr6xymthyl-pyrroIidin-I-yl.' yloxymethyl]-behzonitrile as. a light yeNbw solid. ISP mass spectrum, m/e : 374. 4 (M+1 cålculåted ir « 23 723973S3 2", 3 ; r ffi ;--"77 >7^ La Lfll7ii > 7i'4 , . .', 'Example 134. In'analogy to example 1=30 ; o, ii reaction of 4- (4-c behzonitrile, product : of example'130 d), with (R)-2- (hydroxymethyl) pyrrolidm'e, here was6btained : \ (R)-4- [4- (2-hydr6x) eth) -pyrroli yloxymethyl]-benzonitrileas, a light yeUpw calcuTated for C23T=I23N3O'2 : 374) :., ,. ;,.' xamv e 35 °"s.. 3.., xy. f.... . :. i. '''1 r , 2. f'--t E ,-t y, , rPg 4'r. . ; , r.. ., wy- :. inde ' (9 _ 3 h')-q". ..... , . t, Y. °, . xe', :.,. m :. ; 'r _ _.' ;. s'. . . } ','Example I35'°' In arialogy to-eazriple 130 ; arn, reactiori of 4 (4 criloio =. =inefihyl=cuiiiolm-7=yloXyiinetliyl)- Exam-Dle I berizomtrile rocltact of exa3n le 130: W tti. =3 <tllrneth. Iaiiirn:.. p P) ..,: x _ ).. v Y ) p'ro idln ere wasobtaiiied : (R) =4= [4 ( ; 3.'-diinethylamino. : pyrrolxdin-l-y1)-2-iriefihyl=quirioliri'== A.. :. s-., 1.'. i ; .,, : £.", :- , i,. .,. ,. ., ;', :,.', ;.".''"./'"''j./. ../ ;'Example 13, 6-'-'..,,,'.' ;'.,"....,..,,,..- ino in--7-- calciilateclfbrCz4H'isN4 : 8's) : =' e.-. ''.. : : _ _". : : r ;. , > : : rr, : . ,, : r-. : . ,... .. ,,,, 8, f p, 6,..,, ! ,. :. _.... 4 , _,..,,., :' : _. .,.. r : e a '. . In analo to exani"le 130 ; ori reactioii of 4="4-chilori'o 2riieth 1= uinoTm=7-. lo 'eth 1- gY p Y q Y Y) e p a ;, _t, t.-," . c'. benzonitrile, product oeXample 130'. d, nh, (S) 3' (dimethylairimo) pyirolidirie ; tliere vas obtaiiied: (S 4- [4 (3=dxrrieth lairiino= r, dlidim 1'='l-2=metli I='uiriolin 7.. °' Y.-PXx Y-) Y q was obtained : (S)-4- [4-' (3-dimethylamin6-pyrr6lidin-1-'' pro a : Y. rt,, __. ,. _yme y y tram s was;..,..... : z_,. s k j.' ; r, <. c iåtèdtör4n+ ;-. ? 03 a. 2 i,-tr iA ! ior E M"iL< ;''''' ; S'' r J. _,:. Examle 137 In anatogy to example'1.3'O, on'reaction'of 4= (4, chloro 2=imeth l= uindlu 7 10 ° eth 1- benzbiiitrle; roduc ofeam Te 130t d wi. th..-metho/eth 1'rolidine there was obtamed: (R) -4- [4 (-metho eth l M' rolidin-1-'1 =2-meth'l-uinolin=7- , xym y pYr Y) Y q lo eth 1'-'-lerizomtrie as a Ii lit flirown s, olid I-SP mass's ectrurn; m/e: 3$; ;". 3°.; iCT. +'r. ''

Example 138 In analogy to example 130, on reaction of 4= (4-chloro-2-methyl-quinolin-7-yloxyrimethyl)- ..,'°' :. >.., _. r. '.. benzonitrile, product of example 130 d), W th (S) 2- (metlioxymethyl) pyrrolidrne ;'there. was obtained : (S) 4- [4- (2-memoxymethyl-pyrrolidin-l-yl)-2-. methyl-quinolin ,.. e. .,., _ : ylpxymethyl]-benzQnitrile asalightbrdnblidISP mass spectrum, m/e : 388. 3, (M+l calculated or C24H2sN302 : 0t,,"j/} .,., n In analogy to example 130, on reaction of 4- (4-chlo. ro-2-methyl-quinolin-7-yloxymethyl)- benzonitrile, product of example1130 d) ;, yth (R, S)-, 2 isopropyl=pyrrolidine,, tleie was obtained : (R, S)-4, 54, ;. (ti, sopro ; yi. pdin-i-yi)-2-rneiyl-quinolm-7-yioeiyli- benzbnie'-hydrocNorid GalSMatefbr7N38 ', "- . . ? T-. ! ine, th"r _. _,,. ; y :., , y. ; . :",. p-. .. I. : CM . : i.. F., ,,. ,. 1. :.,". . ;.. . : ^. 3 v ; -v.. S= : ^_. c. lefilated fir : a5'N3a= : 386 ,.. r_t. Y, _. ; G ; : i : F ; . ,,,.. _..... ,.. :..... t :,,, y :...,... x .', 3,. f I. :..., Exarnle 140 In analo to example 130 on reaction of 4. --. cliloro-.,ethyi)- , gy.,, p,. > (4 2, ne Yl, lqrumolin, 7 yloxymethyl) _ benzonitrile,. product of eXample 130 d), wyli. (, S) _ proline nmethyl ester ; vther yvas « obtained : (S)-l- [7- (4-. cyano-benzyloxy)-2-mcthyl-quinolin-4-yl]-pyrrplid . _.. W, T. _. k acicl'rinethyl°est'as ; ahitE solid : f ISFvinass sp-ectriri, m/. e :-0 5, (1I+1-, calculated 01 3"0, in-7-., i'oi-n" 4H23N03 :'402) ''"-'- q erz . :-. s. r'', , '., . . f,, ; t . : .' ; Y ; ; a :. x : M L, . ; T, . , y,., :. . jt. ..'es : a. M, ri,,. d ; : v i ,'t,, 'x' 1i -e.'xti. , t . n c : a. iIl-n, .. '. :'G :". <. ..:,. t Exaxnle 141 :... Iri arialo to earri'le 13U on ieactiori'of 4=; 4c.'chloro 2=ineth 1=' u'nol'in'Z'. 110' '' eth 1- Y P .. y q. ,. y xym y) obtained roducfiof exam 'le 130 d. m. th R : 3=. meth lamino. rolidine there Was. .. I ?,,. _.. ' ;.. ., ),., s.. y .. PYr'...,. obtained : _ (R)- 4- [2,-methyl 4. (3.-methylamyo pyrr, olidm= ; 1 yl)-. quinolin-7-yloxymethyl] ; benzoiiitrile as'a'ellowf, oarn: ISR rnss's ectrum frl/ 373. . IVI+F calculated-dr- y1-1 I-I I. 1. e G23H24N3 ; 73)''

Example 142, In analogy to example 130, on reaction of 4-' (4-chl. oro-2-methyl-quinolin-7-yloxymethyl)- oui benzonitrile, product of example 130 d), with (S)-3- (methylammo) pyrrplidine there was obtained : (S)-4- [2-methyl-4- (3-methylami. n0xpyrolidm-l-yl)-quinolin-7-y benzonitrile as a brown foam. ISP mass spectrum, m/e : 373. 4. (M+I calculated'for C23H24N40 : 373)., ^ ;', [^,,,,-,-,.'< {,, S,,,-. < ;,., Example. 143...,,,, ^,.,".,,,.,., ; b", ;,, < ;, X,. Ã. v i > b t i , t'fi !'^ e, e ?, I benzonitrue, product of example 130d),-with, piperidme&erewasqbtained :. 4- (2-met ,,, ya,, f. : i C S, t ;.,'. ;',,,, _,., ;, I,,, ,, !'c.....,.,. In analogy to example 130, on reacton of 4 hloro 2 methyl-qmnolm 7 y, loxymethyl)- benzonitrile, product of example 130 d), , nth piperidme there was obtamed: 4 (2-methyl- 4-piperidm-1-yl quinoln-7-ylocymetli'yl)-benzonitrile hydrochloride as a yellow solid. on r io of 4-- (. y ... p :,,,.. :.., ., .. .. a ' . ; t, i. :) :, . , r, t, c, r. ,, n-.., In analogy to exariiple 130, on reactiomo4- (4 chloro-2-xnethyl quinolin 7 yloxymethyl)- benzonitrile, product of example 130 d), with mprpholinether. e was pbtaihed :. 4- (2-, .,.,., .,. _.-. methyl-4-morpholin-4-yl-quinolin-7-ylpxymey hydrpchlpride as a light yellow solid. ISP mass spectrum, m/e : 360. 3 (M-t-T calculated, for 22213. 02 : 360). -,. anälogy (,. e ;,, -E ) tua obtamdR. S) --. .. 1 -f : : .... f me4yl-4-iijorpholin-4-, yi-q inolin''-7-vl-o,' . i, 'tl, ,: i't FW4-1 tv ° 1 In analogyto'example, 130; or; reacton vof 4_ (4 chloxo 2=inethy'=ur. riolu=-yloxyiiiethyl)- beriz"onitrile" roduct: of eami Ie 1: 30 ii'w w: tlir R S =-3'dieth larni o iololzne there ras otitairied'R, S 4 =4,3-dith iimnb= roIi. zn'-. 1 2=meth '1-uinolin 7v-' gmeifi enzonitrile hvdrochloride as a liaht r'i ^a. 1 4l5. 4 (M+l^ cai'culåfed br'C2'2H>'iN@2 : *4 7i} 74, ~ì. si-l''-.'t-I'í r ; i- .. .,,.", , c t i t 1 W ° f r lE : u u4.,.. . u'"-y CG } : ; ! F tt. . ., i i ^', ° ; i.,' f. ,,.,.... i. S., 1 ,. _ l, r."i E'n , _.. a y h i1 r I_ r. y r a', 4'_" (, ; i t,, 3.. r. "dithyld-="iid) pyrro i ifte'th-6re, Was ..'..'.-, t. x c. ° x l ; t.,, 3t !, :', f., obit 't.. : I s rt,, v-, In arialogpto exmple 13, O ; : ori ; reaction ;'o4., (clil. oio 2=inethyl : quiriolm=7=ylo :"'etliyl) = . ;,, E ! iLal obtame : 4 [2tr . : t. .. ; . r : t'. li, >ae. Fr-., i. ?'. l a. ' t,. u. i.. ;.... . , _. #, _.,, S-. t-r ;. n, z,..,.,. .,. . ;., s,. :'.,, 9'eux

benzonitrile hydrqchlonde as a brown solid. ISP'mass spectrum, m/e : 421. 4 (M+1'^ . ! l A calculated for C27H24N40 :'421). Example 147 In analogy to example 10 on reactibnof4 (4-cMoro-2-methyl-qu. inolin-7-yloxy benzonitrile, product of example 130 d) ywith (R, S)-4- (pyrrolidin-3-yl)-pyridme there was obtained : (R, S)-4- [2-methyl-4- (3-pyridin-4-yl-pyrrolidin-1-yl)-. quinolin-7-yloxymethyl- .. _...., :, a,.,.. _ _ :.. .- _. : : '-.. > >. : : e,. ; :... : ,. benzonitrile as a white solid. ISP mass spectrum, m/e: 421.4 (M+1 calculated for C27H24N4 ( ? : 4. 2 1) ..'-t ., ;.",.' :,.,. In analogy to example 130, on reaction of 49 (4.-, chioro-2-methyl-quinolin-7-yloxymethyl)- benzonitrile, product of example 130 d) ;. with .. (S)-sl-- (2-pyrrolidinylmethyl) pyrrolidine there was obtairiecl (S)-4 [2=mefihyl-4 (2-pyiroliclm-l'=ylmethyl-pyrrolid. iri'1-yl- - ; y-bidwn in 0 ta p irile : i42 : 6 (M-F lrcalcLiTated-foCaTI-I'3oN4'C : 27). = . e.. ...,., ; ; : .. s, r, =. _ j. i : _ _", ; -... t ;.",. u : _. ; _'' ? : : _. r_.,, , :,.,...,, <3., tIEI : > ; _ _-> : :.',.- .,.. ; :, _. "...'.....,,.. n 7.'.'. _,,. , ... f _ a'..,. b.... , 7.. ; f.. ix) : _, _... f.. t. t'. _4 :... _"- ! ,,..,,.. _...,. _. :.,..... _-.',-,,'. _,.,.,. . ; _'., _'i,'.. ; ., _.,,.,-, r.., ^ ; :.-,..'Y", my ...,... Iri aiialo' to eXain le r1 0 onvreaction of'4'= 4-c'dro=2=meti '1- iiriolin-7 lo-e gy P,.... >, :. ,, ,,, Y q _.,.. Y. . yl) _ lienzomtrile, produt of-exarriple 130 d, With (R ; S).-3- (methylsulfonyl)-pyrrolidine there was obtained : (R, S)-4- [4- (3-m, ethanesulfony. pyrrolidin-, 1-yl)-2-methyl-quinolin-7-.. F.-. a :., : 422. 4' (M'+Tc'alculated-Tdr23H2 422.4 (1VI+'T calcizlatedfor 23Hz3NstO3S 42 ' A... ., x. ,. a,. -; s q°;:., . ,' :' ariyle 150.. a r :."-..,..... ...,..,. ... a. <.... .,.,.., T ° In analogy to'-example iO.'bn reaction of-4cMorp-2-methyl-qumol- benzonitrile, product of example 130, d), wi, th', (R, S). ;-3-methyl-piperidine there. was obtained: (R, S)-4- [2-methyl-4- (3-methyl-piperidin-l-yl)-quinolin-7-yloxymethyl]- z ^. ;. _, 9. t.,'. berizoW tiile hy'drochlor. e asa lght : yel : Iiwsolid ; TSPvrriassspectrxii ; r7e. 372 : 4'. 1+a'v. :..,.. calc-ulate for CZHz5N30 3=) :

Example 1, 51 In analogy to example 130, on reaction of4- (4-chloro-2-methyl-quinolin-7-yloxymethyl)- benzonitrile, product of example 130 d), with i, 4-dioxa-8-azasplro {4. 5}. decane there was obtained: 4- [4- (1, 4-dioxa-8-aza-spiro [4.5] dec-8-yl)-2-methyl-quinolin-7-yloxymethyl]- benzonitrile as a light yellow solid. ISP mass'spectrum, m/e : 416. 4 (M+1 calculated for C25H25N303 : 416i. .....,. : .... In analogy to example 130, on reaction. o, f 4 (4-chloro-2-methyl-quinolin-7-yloxymethyl)- benzonitrile, product of'example. l30 d), S), 3-(hydroxymethyl) piperidine there was obtained: (R, S)-, 4- [4- (3-, hydroxymethyl-piperidin-l, yl)-2-methyl-quinolin-7- -in cal'cultätè'di foí'C24H2s 3'D2 38"- ! i' ;-8"; {''^ . Example A A compound of formula I can be used in a manner known per se as the active ingredient for the production of tablets of the following composition : ....,-,', .., ', , r eoy.. 'y.,'... ..',..." :..-Per tablet ex tablez A Ac, tive. ingzediet4 ;,, y. r l. > ; :'., ;. = 2O mgs, _ y : v : i,. e _ :., Hydrbiyrii'o'pylm6thy1c, u ose 4 r. '"'"-''---L-- YS ! ! ; """""'"'"'"

Example A compbundof £ornula, I.. can be, used in a manner, knoy per se as. the atye ingredient for th ; eprqJE Xgf c'apsu,', es °, of ; eeoi i, ti, o i t". t pw ; T , k ., y L _,, t, ... . _t. ....' Pei caysule...., , Active ingr6dint- : 100io, fii' .. 220. 0 mg' mu, Lactose Talc mg a_, Magnesiuxi stearate P Ov-> . .