FIELD OF THE INVENTION The present invention provides tetracyclic 1,2,3,4,5,6- hexahydroazepino- [4,5-b] indole derivatives having a ring connecting position 6 (N-6) and position 7 (C-7), and more specifically, provides compounds of formula (I) described hereinbelow. These compounds are 5-HT ligands, and are useful for treating diseases wherein modulation of 5-HT activity is desired.

BACKGROUND OF THE INVENTION Serotonin has been implicated in a number of diseases and conditions which originate in the central nervous system. These include diseases and conditions related to sleeping, eating, perceiving pain, controlling body temperature, controlling blood pressure, depression, anxiety, schizophrenia, and other bodily states. R. W. Fuller, Biology of Serotonergic Transmission, 221 (1982); D. J. Boullin, Serotonin in Mental Abnormalities 1: 316 (1978); J.

Barchas, et al., Serotonin and Behavior, (1973). Serotonin also plays an important role in peripheral systems, such as the gastrointestinal system, where it has been found to mediate a variety of contractile, secretory, and electrophysiologic effects.

As a result of the broad distribution of serotonin within the body, there is a tremendous interest in drugs that affect serotonergic systems. In particular, receptor-specific agonists and antagonists are of interest for the treatment of a wide range of disorders, including anxiety, depression, hypertension, migraine, obesity, compulsive disorders, schizophrenia, autism, neurodegenerative disorders (e. g. Alzheimer's disease, Parkinsonism, and

Huntington's chorea), and chemotherapy-induced vomiting. M. D. Gershon, et al., The Peripheral Actions of 5-Hydroxytryptamine, 246 (1989); P. R. Saxena, et al., Journal of Cardiovascular Pharmacology, 15: Supplement 7 (1990).

The major classes of serotonin receptors (5-HT, 7) contain fourteen to eighteen separate receptors that have been formally classified. See Glennon, et al., Neuroscience and Behavioral Reviews, and D.

Hoyer, et al. Pharmacol. Rev. Recently discovered information regarding subtype identity, distribution, structure, and function suggests that it is possible to identify novel, subtype specific agents, having improved therapeutic profiles (e. g. fewer side effects).

For example, the 5-HT2family of receptors is comprised of 5- HT2A, 5-HT2B, and 5-HT2C subtypes, which have been grouped together on the basis of primary structure, secondary messenger system, and operational profile.

All three subtypes are G-protein coupled, activate phospholipase C as a principal transduction mechanism, and contain a seven-transmembrane domain structure. There are distinct differences in the distribution of the three 5-HT2 subtypes. The 5-HT2B and 5-HT2A receptors are widely distributed in the periphery, while the 5-HT2c receptor has been found only in the central nervous system, being highly expressed in many regions of the human brain. See G.

Baxter, et al. Trends in Pharmacol. Sci. 1995, 16,105-110.

Subtype 5-HT2Ahas been associated with effects including vasoconstriction, platelet aggregation, and bronchoconstriction, while subtype 5- HT2c has been associated with diseases that include depression, anxiety, obsessive compulsive disorder, panic disorders, phobias, psychiatric syndromes, and obesity. Very little is known about the pharmacologic role of the 5-HT2B receptor. See F. Jenck, et al., Exp. Opin. Invest. Drugs, 1998,7,1587-1599; M.

Bos, et al., J. Med. Chem., J. R. Martin, et al., The Journal of Pharmacology and Experimental Therapeutics, 1998, 286,913-924; S. M.

Bromidge, et al., J. Med. Chem., G. A. Kennett, Drugs,

456-470; and A. Dekeyne, et al., Neuropharmacology, 1999,38,415- 423.

United States Patent Number 3,676,558, issued July 11,1972, discloses compositions comprising specific 6-alkyl-1,2,3,4,5,6- hexahydroazepino [4,5-b] indole compounds. The compositions are reported to be useful to suppress hunger in mammals. This patent also discloses a method for inducing anorexia in obese subjects to produce weight loss. The azepino [4,5- b] indole compounds disclosed in this patent lack the ring connecting the 6- position and the 7-position that is present in the compounds of the instant invention.

United States Patent Number 3,839,357, issued October 1,1974, discloses specific 1,2,3,4,5,6-hexahydroazepino [4,5-b] indole compounds, which are reported to have sedative or tranquilizing action. The azepino [4,5-b] indole compounds disclosed in this patent also lack the ring connecting the 6-position and the 7-position that is present in the compounds of the instant invention.

There is currently a need for pharmaceutical agents that are useful to treat diseases and conditions that are associated with 5-HT receptors.

SUMMARY OF THE INVENTION In accordance with the present invention, novel compounds which demonstrate useful biological activity, and particularly activity as 5-HT receptor ligands, are provided. Thus, the present invention provides a compound of formula I: (I) wherein,

each R, is independently hydroxy, nitro, halo, cyano, trifluoromethyl, trifluoromethoxy, C1-7alkanoyl,C1-C1-7alkoxy, 7alkoxycarbonyl, Cl 7alkanoyloxy, aryl, heteroaryl,-S (O) mNRaRb, NRCRd, -S (O) mRe, or-C (=O) NRaRb, wherein any C1-7alkyl, C1-7alkoxy, C1-7alkanoyl, C1-7alkoxycarbonyl ro C1-7alknaoyloxy of R1 is optionally partially unsaturated and is optionally substituted with aryl, aryloxy, heteroaryl, heteroaryloxy, hydroxy, nitro, halo, cyano, C1-7alkoxy, C1-7alkanoyl, C1-7alkoxycarbonyl, C1- 7alkanoyloxy,-S (O) mRe,-S (O) mNRaRb, NRRd, or-C (=O) NR, R,; R2 is hydrogen, C1-7alkyl, C1-7alkanoyl, arylcarbonyl, aryl, (aryl) C1-7alkyl, C1-7alkoxycarbonyl, aryloxycarbonyl, arylsulfonyl, or (aryl) C 7alkoxycarbonyl; X and Y together are a 2,3, or 4 membered saturated or partially unsaturated chain comprising one or more carbon atoms and optionally comprising one oxy (-O-), thio (-S-), sulfinyl (-SO-), sulfonyl (S (O) 2-), or NRf in the chain; wherein the chain is optionally substituted on each carbon with oxo (=0), thioxo (=S),-NRR-S (O) pros, or-ORt, or with one or two substituents independently selected from the group consisting of C1-7alkyl, (C1-7alkoxy) C1- (aryl)C1-7alkyl,heteroaryl,(heteroaryl)C1-7alkyl,and7alkyl,a ryl, (aryl) oxyC1-7alkyl ; or wherein the chain is optionally substituted on a carbon with a 4,5, or 6 membered spirocyclic carbon ring; or wherein the chain is optionally substituted on two adjacent atoms with a 2,3, or 4 membered alkylene chain (e. g.-CH2CH2-,-CH2CH2CHZ, or-CH2CH2CH2CH2-) forming a ring that is fused to the ring comprising X and Y; each m is independently 0,1, or 2; nisO, 1,2, or3; 0,1,or2;pis each Ra and Rb is independently hydrogen, Cl 7alkyl, aryl, (aryl) C1-7alkyl, heteroaryl, or (heteroaryl) Cl 7alkyl; or Ra and Rbtogether with the nitrogen to which they are attached form a pyrrolidino, piperidino, morpholino, or thiomorpholino ring;

each Re and Rd is independently hydrogen, C1-7alkyl, C1-7alkanoyl, C1-7alkoxycarbonyl, aryl, (heteroaryl)C1-7alkyl,heteroaryl, arylcarbonyl, heteroarylcarbonyl, aryloxycarbonyl, or heteroaryloxycarbonyl; or Rc and Rd together with the nitrogen to which they are attached form a pyrrolidino, piperidino, morpholino, or thiomorpholino ring; each independentlyhydrogen,C1-7alkyl,aryl,(aryl)C1-7alkyl,is heteroaryl, or (heteroaryl) C1-7alkyl ; Rf is hydrogen, C1-7alkyl, aryl, (aryl)C1-7alkyl, heteroaryl, (heteroaryl) C, 7alkyl, or is a bond to a 2,3, or 4 membered alkylene chain that forms a ring that is fused to the ring comprising X and Y; each Rq and Rr is independently hydrogen, C1-7alkyl, aryl, (aryl) C, 7alkyl, heteroaryl, or (heteroaryl) C, 7alkyl; or Rq and Rrtogether with the nitrogen to which they are attached form a pyrrolidino, piperidino, morpholino, or thiomorpholino ring; R. is C1-7alkyl, aryl, (aryl)C1-7alkyl, heteroaryl, or (heteroaryl) C 7alkyl; and R, is hydrogen, C,-7aUql, aryl, (aryl) C, 7alkyl, heteroaryl, or (heteroary)C1-7alkyl; wherein any aryl or heteroaryl ring of RI, R2, X, Y, Ra-Rf, or Rq-Rt is optionally substituted with one or more (e. g. 1,2,3, or 4) substituents independently selected from halo, hydroxy, cyano, nitro, trifluoromethyl, trfluiormethoxy, phenyl,sulfonyl,NRjRk,or-C1-7alkoxy, C (=O) NR&; wherein each R, and Rk is independently hydrogen, Cl, alkyl, C1-7alkanoyl, C1-7alkoxycarbonyl, aryl, (aryl) C"alkyl, arylcarbonyl, or aryloxycarbonyl; or Rj and Rk together with the nitrogen to which they are attached form a pyrrolidino, piperidino, morpholino, or thiomorpholino ring; or a pharmaceutically acceptable salt thereof; provided Y is not oxy, thio, sulfinyl, or NRf; and provided X and Y together are not a 2-membered unsaturated chain; and

provided no carbon of X and Y is bonded to more than one oxy, thio, sulfinyl, or NRf.

In another aspect, the present invention also provides: a pharmaceutical composition comprising a compound of formula I, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient (the composition preferably comprises a therapeutically effective amount of the compound or salt), a method for treating a disease or condition in a mammal (e. g. a human) wherein a 5-HT receptor is implicated and modulation of a 5-HT function is desired comprising administering a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt thereof to the mammal, a method for treating or preventing a disease or disorder of the central nervous system in a mammal comprising administering a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt thereof to the mammal, a compound of formula (I) or a pharmaceutically acceptable salt thereof for use in medical diagnosis or therapy (e. g. the treatment or prevention of 5-HT related disease such as anxiety, obesity, depression, or a stress related disease), the use of a compound of formula I, or a pharmaceutically acceptable salt thereof to prepare a medicament useful for treating or preventing a disease or disorder of the central nervous system in a mammal, and a method for modulating 5-HT receptor function, comprising administering an effective modulatory amount of a compound of formula I, or a pharmaceutically acceptable salt thereof.

The invention also provides novel intermediates and processes disclosed herein that are useful for preparing compounds of formula I.

DESCRIPTION OF THE FIGURES Figures 1-6 illustrate synthetic processes and intermediates useful for preparing compounds of the invention.

DETAILED DESCRIPTION OF THE INVENTION The compounds of the invention are useful for treating or preventing diseases or disorders of the central nervous system. Specific diseases or disorders of the central nervous system for which a compound of formula I may have activity include, but are not limited to: obesity, depression, schizophrenia, schizophreniform disorder, schizoaffective disorder, delusional disorder, a stress related disease (e. g. general anxiety disorder), panic disorder, a phobia, obsessive compulsive disorder, post-traumatic-stress syndrome, immune system depression, a stress induced problem with the urinary, gastrointestinal or cardiovascular system (e. g., stress incontinence), neurodegenerative disorders, autism, chemotherapy-induced vomiting, hypertension, migraine, headaches, cluster headaches, sexual dysfunction in a mammal (e. g. a human), addictive disorder and withdrawal syndrome, an adjustment disorder, an age-associated learning and mental disorder, anorexia nervosa, apathy, an attention-deficit disorder due to general medical conditions, attention-deficit hyperactivity disorder, behavioral disturbance (including agitation in conditions associated with diminished cognition (e. g., dementia, mental retardation or delirium)), bipolar disorder, bulimia nervosa, chronic fatigue syndrome, conduct disorder, cyclothymic disorder, dysthymic disorder, fibromyalgia and other somatoform disorders, generalized anxiety disorder, an inhalation disorder, an intoxication disorder, movement disorder (e. g., Huntington's disease or Tardive Dyskinesia), oppositional defiant disorder, peripheral neuropathy, post-traumatic stress disorder, premenstrual dysphoric disorder, a psychotic disorder (brief and long duration disorders, psychotic disorder due to medical condition, psychotic disorder NOS), mood disorder (major depressive or bipolar disorder with psychotic features) seasonal affective disorder, a sleep disorder, a specific

development disorder, agitation disorder, selective serotonin reuptake inhibition (SSRI)"poop out"syndrome or a Tic disorder (e. g., Tourette's syndrome).

The following definitions are used, unless otherwise described: halo is fluoro, chloro, bromo, or iodo. Alkyl, alkoxy, etc. denote both straight and branched groups; but reference to an individual radical such as"propyl" embraces only the straight chain radical, a branched chain isomer such as "isopropyl"being specifically referred to. When alkyl can be partially unsaturated, the alkyl chain may comprise one or more (e. g. 1,2,3, or 4) double or triple bonds in the chain.

Aryl denotes a phenyl radical or an ortho-fused bicyclic carbocyclic radical having about nine to ten ring atoms in which at least one ring is aromatic. Heteroaryl denotes a radical of a monocyclic aromatic ring containing five or six ring atoms consisting of carbon and 1,2,3, or 4 heteroatoms each selected from the group consisting of non-peroxide oxygen, sulfur, and N (X) wherein X is absent or is H, O, C, 4alkyl, phenyl or benzyl, as well as a radical of an ortho-fused bicyclic heterocycle of about eight to ten ring atoms derived therefrom, particularly a benz-derivative or one derived by fusing a propylene, trimethylene, or tetramethylene diradical thereto.

It will be appreciated by those skilled in the art that compounds of the invention having a chiral center may exist in and be isolated in optically active and racemic forms. Some compounds may exhibit polymorphism. It is to be understood that the present invention encompasses any racemic, optically- active, polymorphic, tautomeric, or stereoisomeric form, or mixture thereof, of a compound of the invention, which possesses the useful properties described herein, it being well known in the art how to prepare optically active forms (for example, by resolution of the racemic form by recrystallization techniques, by synthesis from optically-active starting materials, by chiral synthesis, or by chromatographic separation using a chiral stationary phase) and how to determine 5-HT activity using the standard tests which are well known in the art.

The carbon atom content of various hydrocarbon-containing moieties is indicated by a prefix designating the minimum and maximum number of carbon atoms in the moiety, i. e., the prefix C j indicates a moiety of the integer"i"to the integer"j"carbon atoms, inclusive. Thus, for example, C, 7alkyl refers to alkyl of one to seven carbon atoms, inclusive.

The compounds of the present invention are generally named according to the IUPAC or CAS nomenclature system. Abbreviations which are well known to one of ordinary skill in the art may be used (e. g."Ph"for phenyl, "Me"for methyl,"Et"for ethyl,"h"for hour or hours and"rt"for room temperature).

Specific and preferred values listed below for radicals, substituents, and ranges, are for illustration only; they do not exclude other defined values or other values within defined ranges for the radicals and substituents Specifically, Cl, alkyl can be methyl, ethyl, propyl, isopropyl, butyl, iso-butyl, sec-butyl, pentyl, 3-pentyl, hexyl, or heptyl; C, 7aLkoxy can be methoxy, ethoxy, propoxy, isopropoxy, butoxy, iso-butoxy, sec-butoxy, pentoxy, 3-pentoxy, hexyloxy, 1-methylhexyloxy, or heptyloxy; Ct, aLkanoyl can be acetyl, propanoyl, butanoyl, pentanoyl, 4-methylpentanoyl, hexanoyl, or heptanoyl; Cl, aLkoxycarbonyl can be methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, pentoxycarbonyl, hexyloxycarbonyl, or heptyloxycarbonyl; C"aLkanoyloxy can be acetoxy, propanoyloxy, butanoyloxy, isobutanoyloxy, pentanoyloxy, hexanoyloxy, or heptanoyloxy; aryl can be phenyl, indenyl, or naphthyl; and heteroaryl can be furyl, imidazolyl, triazolyl, triazinyl, oxazoyl, isoxazoyl, thiazolyl, isothiazoyl, pyrazolyl, pyrrolyl, pyrazinyl, tetrazolyl, pyridyl, (or its N-oxide), thienyl, pyrimidinyl (or its N-oxide), indolyl, isoquinolyl (or its N-oxide) or quinolyl (or its N-oxide).

A specific value for R, is hydroxy, nitro, halo, cyano, trifluoromethyl, trifluoromethoxy, Cl 7alkyl, Cl 7alkoxy, C,, aLkanoyl, C,

aryl,heteroaryl,-S(O)mNRaRb,NRcRd,7alkoxycarbonyl,C1-7alkano yloxy, -S (O) mRe, or-C (=O) NRaRb, wherein any C1-7alkyl, C1-7alkoxy, C1-7alkanoyl, C1-7alkoxycarbonyl, or C, 7aLkanoyloxy of R, is optionally substituted with aryl, aryloxy, heteroaryl, heteroaryloxy, hydroxy, nitro, halo, cyano, C1-7alkoxy, C1-7alkanoyloxy,-S(O)mRe,-S(O)mNRaRb,C1-7alkanoyl,C1-7alkoxy carbonyl, NRcRd,or-C(=O)NRaRb.

A specific value for R, is hydroxy, nitro, halo, cyano, trifluoromethyl, trifluoromethoxy, C1-7alkanoyl,C1-C1-7alkoxy, aryl,heteroaryl,-S(O)mNRaRb,NRcRd,7alkyoxycarbonyl,C1-7alkan oyloxy, -S (O) R3, or-C (=O) NRaRb, wherein any C1-7alkyl or C1-7alkoxy of R1 is optionally substituted with aryl, aryloxy, heteroaryl, heteroaryloxy, hydroxy, nitro, halo, cyano, C1-7alkoxy, C1-7alkanoyl, C1-7alkoxycarbonyl, C1-7alkanoyloxy, NRcRd,or-C(=O)NRaRb.-S(O)mRc,-S(O)mNRaRb, A specific value for R, is hydroxy, nitro, halo, cyano, trifuoromethyl, trifluoromethoxy, C1-7alkanoyl,C1-C1-7alkoxy, aryl,heteoaryl,-S(O)mNRaRb,NRcRd,7alkoxycarbonyl,C1-7alkanoy loxy, -S (O) mure, or-C (=O) NR, Rb, wherein any Cl, alkyl is optionally substituted with aryl, aryloxy, heteroaryl, heteroaryloxy, hydroxy, nitro, halo, cyano, C1-7alkoxy, C1-7alkanoyloxy,-S(O)mRe,-S(O)mNRaRb,C1-7alkanoyl,C1-7alkoxy carbonyl, NRcRd, or -C(=O)NRaRb.

A specific value for R, is hydroxy, nitro, halo, cyano, rrifluoromethyl, trifluormethoxy, C1-7alkanoyl,C1-C1-7alkoxy, 7alkoxycarbonyl, C1-7alkanoyloxy, aryl, heteroaryl,-S (O) mNRaRb, NR¢Rd, -S (O) mRes or-C (=O) NRaRb.

A specific value for R, is independently C,, aLkyl, C,, aLkoxy, trifluoromethyl, or halo.

A specific value for R2 is hydrogen.

A specific value for R is C, 4alkyl, C,alkanoyl, arylcarbonyl, (aryl) C, 2alkyl, C, 4aLkoxycarbonyl, aryloxycarbonyl, arylsulfonyl, or

(aryl) methoxycarbonyl, wherein any aryl is optionally substituted with 1,2, or 3 substituents independently selected from C, 4alkyl and trifluoromethyl.

A specific value for R2 is methyl, ethyl, propyl, isopropyl, acetyl, tert-butoxycarbonyl, benzyloxycarbonyl, benzyl, orp-toluenesulfonyl.

A specific value for n is 1,2, or 3.

A specific value for n is 0.

A specific group of compounds are compounds of formula (I) wherein n is 0. It will be clear to one skilled in the art that when n is 0, the benz ring of the indole in formula (I) is substituted with hydrogens.

A specific group of compounds are compounds of formula I wherein X and Y together are a 2,3, or 4 membered saturated or partially unsaturated chain comprising one or more carbon atoms and optionally comprising one oxy (-O-), thio (-S-), sulfinyl (-SO-), sulfonyl (S (0) 2-), or NRf in the chain; wherein the chain is optionally substituted on each carbon with oxo (=0), thioxo (=S),-NRqRr,-S (O) pRs, or-ORt, or with one or two substituents independently selected from the group consisting of C1-7alkyl, (C1-7alkoxy)C1- , alkyl, aryl, (aryl) CI 7alkyl, heteroaryl, (heteroaryl) CI 7alkyl, and (aryl) oxyCI 7alkyl.

A specific group of compounds are compounds of formula I wherein X and Y together are a 2,3, or 4 membered saturated or partially unsaturated chain comprising one or more carbon atoms and optionally comprising one oxy (-O-), thio (-S-), sulfinyl (-SO-), sulfonyl (S (0) 2-), or NRf in the chain; wherein the chain is optionally substituted on each carbon with oxo (=0), thioxo (=S),-NRqR,-S (O) PR,, or-ORt.

A specific group of compounds are compounds of formula I wherein X and Y together are a 2,3, or 4 membered saturated or partially unsaturated chain comprising one or more carbon atoms and optionally comprising one oxy (-O-), thio (-S-), sulfinyl (-SO-), sulfonyl (S (0) 2-), or NRf in the chain; wherein the chain is optionally substituted on each carbon with one or two substituents independently selected from the group consisting of Cl 7alkyl,

(aryl)C1-7alkyl,heteroaryl,(heteroaryl)C1-7alkyl,and(C1-7alk oxy)C1-7alkyl,aryl, (aryl) oxyC, 7alkyl.

A specific group of compounds are compounds of formula I wherein X and Y together are a 2,3, or 4 membered chain comprising one or more carbon atoms and optionally comprising one oxy (-O-), thio (-S-), sulfinyl (-SO-), sulfonyl (S (0) 2-), or NRf in the chain; wherein the chain is optionally substituted on each carbon with oxo (=O), hydroxy, or C, 7aLkoxy, or with one or two substituents independently selected from the group consisting of C, 7alkyl, (C, 7alkoxy) C, 7alkyl, aryl, (aryl) CI, alkyl, heteroaryl, (heteroaryl) C1-7alkyl and (aryl) oxyCI 7alkyl; and wherein the chain is optionally substituted on two adjacent atoms with a 2,3, or 4 membered alkylene chain forming a ring that is fused to the ring comprising X and Y.

A specific group of compounds are compounds of formula I wherein X and Y together are a 2,3, or 4 membered chain comprising one or more carbon atoms and optionally comprising one oxy (-O-), thio (-S-), sulfinyl (-SO-), sulfonyl (S (0) 2-), or NRf in the chain; wherein the chain is optionally substituted on each carbon with oxo (=O), hydroxy, (aryl) oxy, heteroaryl (oxy), or Cl 7alkoxy, or with one or two substituents independently selected from the group consisting of Cl 7alkyl, (Cl, alkoxy) CI, alkyl, aryl, (aryl)C1-7alkyl, heteroaryl, (heteroaryl) C1-7alkyl, and (aryl) oxyC1-7alkyl ; and wherein the chain is optionally substituted on two adjacent atoms with a 2,3, or 4 membered alkylene chain forming a ring that is fused to the ring comprising X and Y.

A specific group of compounds are compounds of formula I wherein X and Y together are a 2,3, or 4 membered carbon chain wherein the chain is optionally substituted on each carbon with oxo (=O), hydroxy, or C, 7alkoxy, or with one or two substituents independently selected from the group consisting of Cl 7alkyl, (C, 7aLkoxy) C, 7alkyl, aryl, (aryl) C, 7alkyl, heteroaryl, (heteroaryl) CI 7alkyl and (aryl) oxyCI, alkyl.

A specific group of compounds are compounds of formula I wherein X and Y together are a 2,3, or 4 membered carbon chain wherein the

chain is optionally substituted on each carbon with oxo (=O), hydroxy, (aryl) oxy, heteroaryl (oxy) or C, 7alkoxy, or with one or two substituents independently selected from the group consisting of C1-7alkyl, (C1-7alkoxy)C1-7alkyl, aryl, (aryl) C1-7alkyl, heteroaryl, (heteroaryl) C, 7alkyl, and (aryl) oxyC, 7alkyl.

A specific group of compounds are compounds of formula I wherein X and Y together are a 2 or 3 membered carbon chain optionally substituted on each carbon with oxo or hydroxy, or with one or two C, 7alkyl.

A specific group of compounds are compounds of formula I wherein X is-O-,-S-, or-C (Rg) (Rh)-, wherein Rg and Ré are each independently hydrogen aryl,(aryl)C1-7alkyl,heteroaryl,(C1-7alkody)C1-7alkyl, (heteroaryl) C1-7alkyl or (aryl) oxyCI 7alkyl, or Rg and Rh together are oxo.

A specific group of compounds are compounds of formula I wherein Y is-C (Rg) (Rh)-, -C(Rg)(Rh)C(Rg)(Rh)-, -C(Rg)(Rh)C(Rg)(Rh)C(Rg)(Rh)-, -C (Rg) (Rh)C(=O)-, -C(Rg)Rh)C(Rg)(Rh)C(=O)-, -C(=O) C (Rg) (Ri)-, or -C (=O) C (Rg)(Rh)C(Rg)(Rh)-, and each Rg and Rb is independently hydrogen or C1-7alkyl.

A specific group of compounds are compounds wherein X is -O-, -S-, or -C(Rg)(Rh)-; and Y is -C(Rg)(Rh)C(Rg)(Rh)-,whereinor each Rg and Rh is independently hydrogen or Cl, alkyl.

A specific group of compounds are compounds wherein X is -O- or-S- ; and Y is-C (Rg) (Rh) C (=O)-,-C (=O) C (Rg) (Rh)-, or-C (Rg) (Rh)C C (Rg) (Rh)-, wherein each Rg and Ru ils independently hydrogen or C1-7alkyl.

A specific group of compounds are compounds wherein X and Y together are-CH (Rg) CH (Rg)-,-CH (Rg) CH (Rg) CH (Rg)-,- -CH(Rg)CH(Rg)CH(Rg)CH(Rg)-,-C(Rg)=C(Rg)CH(Rg)-, -C (Rg) =C (Rg) CH (Rg) CH (Rg)-,-CH (Rg) C (Rg) =C (Rg) CH (Rg)-, -O-CH (Rg) CH (Rg)-,-O-CH (Rg) CH (Rg) CH(Rg)-, -S-CH(Rg) CH (Rg)-, -S-CH (Rg) CH (Rg) CH (Rg)-,-S (O)-CH(Rg) CH (Rg)-, -S (O)-CH (Rg)CH CH (Rg) CH (Rg)-,-S (O) 2-CH (Rg) CH (Rg)-, -S (O) 2-CH (Rg) CH (Rg) CH (Rg)-, -NRf-CH(Rg) CH (Rg)-,

-NRf-CH (Rg) CH (Rg) CH (Rg)-,-CH (Rg) C (=O)-,-CH (Rg) CH(Rg)C(=O)-, -CH (Rg) CH (Rg) CH (Rg) C (=O)-,-CH (Rg) OC (=O)-,-CH (Rg) CH (Rg) OC (=O)-, -OCH (Rg) C (=O)-, or-OCH (Rg) CH (Rg) C (=O)- ; wherein each Rg is independently hydrogen, (aryl)C1-7alkylor(aryl)oxyC1-7alkyl.aryl, A specific group of compounds are compounds wherein X and Y together are-CH (Rg) CH2-,-CH (Rg) CH (Rg) CH2-,-CH (Rg) CH (Rg) CH (Rg) CH2-, -CH=CHCH,-,-CH=CHCH (Rg) CH2-,-CH (Rg) CH=CHCH~2^-, -O-CH2CH2-, -S-CH2CH(Rg)CH2-,-S(O)-CH2CH2-,-O-CH2CH(Rg)CH2-,-S-CH2CH2-, -S(O)2-CH2CH(Rg)CH2-,-S(O)-CH2CH(Rg)CH2-,-S(O)2-CH2CH2-, -CH2C)=O)-,-CH(Rg)CH2C(=O)-,-NRf-CH2CH2-,-NRf-CH2CH(Rg)CH2-, -CH(Rg)CH2OC(=O)-,-CH(Rg)CH(Rg)CH2C(=O)-,-CH2OC(=O)-, -OCH2C (=O)-, or-OCH2CH2C (=O)- ; wherein each Rg is independently -NRqRr, -S (O) pRs, or-OR,.

A specific group of compounds are compounds wherein X and Y together are-CH (Rg) CH (Rg)-,-CH (Rg) CH (Rg) CH (Rg)-,-C (Rg) =C (Rg)CH(Rg)-, -S(O)-CH(Rg)CH(Rg)-,-O-CH(Rg)CH(Rg)-,-S-CH(Rg)CH(Rg)-, -CH(Rg)C(=O)-,-S(O)2-CH(Rg)CH(Rg)-,-NRf-CH(Rg)CH(Rg)-, -CH(Rg)CH(Rg)C(=O)-, -CH(Rg)OC(=O)-, -OCH(Rg)C(=O)-; wherein each Rgis independently hydrogen or Cl, alkyl.

A specific group of compounds are compounds wherein X and Y together are-CH (Rg) CH (Rg)-,-CH (Rg)CH (Rg) CH (Rg)-,-C (Rg) =C (Rg) CH (Rg)-, -S(O)-CH(Rg)CH(Rg)-,-O-CH(Rg)CH(Rg)-,-S-CH(Rg)CH(Rg)-, -S (O) 2-CH (RJCH (Rg)-,-NRrCH (Rg) CH (Rg)-, or-CH (Rg) CH (Rg) C (-0)- ; wherein each Rugis independently hydrogen, C, 7aLkyl, or together with an Rg on an adjacent carbon atom forms a fused 4,5, or 6, membered carbocyclic ring.

A specific group of compounds are compounds wherein X and Y together are-CH (Rg) CH (Rg)-,-CH (Rg) CH (Rg) CH (Rg)-,-O-CH (Rg) CH (Rg)-, -S-CH (Rg) CH(Rg)-; wherein each Rg is independently hydrogen, C1-7alkyl, aryl, or (aryl)C1-7alkyl.

A specific group of compounds are compounds wherein X and Y together are-CH2CH2CH2-,-CH2CH2C (CH3) H-,-CH2C (CH3) HCH2-, -C (CH3) HCH2CH2-,-CH2CH2-,-CH2C (CH3) H-,-C (CH3) HC (CH3) H-,- -CH (Rg) CH (Rg)-,-O-CH2CH2-,-O-C (CH3) HCH2-, or-S-CH2CH2-.

A specific group of compounds are compounds wherein X and Y together are-CH2CH2-,-CH2CH2CH2-,-CH=CHCH2-,-O-CH2CH2-, -S(O)2-CH2CH2-,-NRf-CH2CH2-,-CH2C(=O)-,-S-CH2CH2-,-S(O)-CH2C H2-, -CH2CH2C (=O)-,-CH20C (=O)-, or-OCH2C (=O)-.

A specific group of compounds are compounds of formula (I) wherein X and Y together are-CH (Rg) CH2-,-CH (Rg) CH (Rg) CH2-, or -O-CH2CH2-, wherein each Rg is independently -NRqRf, -S(O)pRs, -ORt, C1-7alkyl, (C, 7aLkoxy) C, 7alkyl, aryl, (aryl) C, 7aLkyl, heteroaryl, (heteroaryl)C1-7alkyl, or (aryl)oxyC1-7alkyl.

A specific group of compounds are compounds of formula (I) wherein X and Y together are-C (=O) CH2-,-CH2C (=O)-,-C (=S) CH2-, -CH2C (=S)-,-C (=O) CH2CH2,-CH2C (=0) CH2-,-CH2CH2C (=)-, -C (=S) CH2CH2-,-CH2C (=S) CH2-, or -CH2CH2C(=S)-.

A specific group of compounds are compounds wherein n is 1 and C1-7alkyl,C1-7alkoxy,orhalo.R1is A specific group of compounds are compounds wherein n is 1 and Ri is methyl, methoxy, chloro, or fluoro.

A specific group of compounds are compounds wherein X and Y together are a 2,3, or 4 membered saturated or partially unsaturated chain comprising one or more carbon atoms and optionally comprising one oxy (-O-), thio (-S-), sulfinyl (-SO-), sulfonyl (S (0) 2-), or NRf in the chain; wherein the chain is optionally substituted on each carbon with oxo (=O), hydroxy, or Cl 7alkoxy, or with one or two substituents independently selected from the group C1-7alkyl,(C1-7alkoxy)C1-7alkyl,aryl,(aryl)C1-7alkyl,of heteroaryl, (heteroaryl) C, 7aLkyl, and (aryl) oxyC,. 7alkyl; or wherein the chain is optionally substituted on a carbon with a 4,5, or 6 membered spirocyclic carbon

ring; or wherein the chain is optionally substituted on two adjacent atoms with a 2,3, or 4 membered alkylene chain (e. g.-CHzCH2-,-CH2CH2CH2, or -CH2CH2CH2CH2-) forming a ring that is fused to the ring comprising X and Y; When X and Y together, or R,, is a"partially unsaturated"group, such group may comprise one or more (e. g. 1 or 2) carbon-carbon double or triple bonds. For example, when R, is a partially unsaturated C, 7aLkyl, it can be vinyl, allyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1,3- butadienyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-hexenyl, 2- hexenyl, 3-hexenyl, 4-hexenyl, 2,4-hexadienyl, 5-hexenyl, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 5-hexene-1-ynyl, 2-hexynyl, 3-hexynyl, 3-hexen-5-ynyl, 4-hexynyl, or 5-hexynyl.

Specifically, the invention also provides a method for treating or preventing anxiety, obesity, depression, schizophrenia, a stress related disease (e. g. general anxiety disorder), panic disorder, a phobia, obsessive compulsive disorder, post-traumatic-stress syndrome, immune system depression, a stress induced problem with the gastrointestinal or cardiovascular system, or sexual dysfunction in a mammal (e. g. a human) comprising administering a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt thereof to the mammal.

Specifically, the invention also provides a method of treating or preventing anxiety, obesity, depression, or a stress related disease, comprising administering to a mammal (e. g. a human) in need of such treatment, a therapeutically effective amount of a compound of formula a) or a pharmaceutically acceptable salt thereof.

Specifically, the invention also provides the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof to prepare a medicament for treating or preventing anxiety, obesity, depression, schizophrenia, a stress related disease (e. g. general anxiety disorder), panic disorder, a phobia, obsessive compulsive disorder, post-traumatic-stress

syndrome, immune system depression, a stress induced problem with the gastrointestinal or cardiovascular system, or sexual dysfunction in a mammal (e. g. a human),.

Specifically, the invention also provides the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof to prepare a medicament for treating or preventing anxiety, obesity, depression, or a stress related disease in a mammal (e. g. a human).

The invention also provides processes and intermediates useful for preparing compounds of formula (I). For example, an intermediate useful for preparing a compound of formula (I) wherein R2 is hydrogen, is a corresponding compound of formula (I) wherein R2 is a suitable protecting group. Thus the invention provides a compound of formula (I) wherein R2 is a suitable protecting group, and wherein RI, X, Y, and n have any of the values, specific values or prefered values defined herein. Suitable amine protecting groups, as well as methods for their preparation and removal are well known in the art, for example, see Greene, T. W.; Wutz, P. G. M."Protecting Groups In Organic Synthesis"third edition, 1999, New York, John Wiley & sons, Inc.

Prefered protecting groups include benzyloxycarbonyl (CBZ) and benzoyl.

The invention also provides intermediate compounds of formula 3,9,10,11,13,15, and 17-20 as shown in Figures 1-6, wherein R2 is a protecting group.

The invention also provides intermediate salts that are useful for preparing or purifying compounds of formula (I). Suitable methods for preparing salts are known in the art and are disclosed herein. For example, the preparation of an oxylate salt is shown in Example 41. As will be apparent to one skilled in the art, such salts can be converted to the corresponding free-base or to another salt using known methods.

For example, compounds of formula I wherein R2is Cl, alkyl, Cl 4alkanoyl, arylcarbonyl, (aryl) CI 2alkyl, Cl 4alkoxyvarbonyl, aryloxycarbonyl, arylsulfonyl, or (aryl) methoxycarbonyl, wherein any aryl is optionaly substituted

with 1,2, or 3 substituents independently selected from 4alkyl and trifluoromethyl, are particularly useful as intermediates for preparing corresponding compounds of formula I wherein R2 is hydrogen. Preferred compounds of formula I that are useful for preparing compounds of formula I wherein R2 is hydrogen are compounds wherein R2 is methyl, ethyl, propyl, isopropyl, acetyl, tert-butoxycarbonyl, benzyloxycarbonyl, benzyl, orp- toluenesulfonyl.

The invention also provides a method for preparing a compound of formula (I) wherein R2 is hydrogen comprising deprotecting a corresponding compound of formula (I) wherein R2 is a suitable nitrogen protecting group.

Compounds of the invention can generally be prepared using the synthetic schemes illustrated in Figures 1-6. Starting materials can be prepared by procedures described in these schemes or by procedures that would be well known to one of ordinary skill in organic chemistry. The variables used in the Schemes are as defined below or as in the claims.

Compounds of formula I can be prepared by reactions outlined in Figure 1. Step 1 involves formation of intermediate N-nitroso compounds by treatment with isoamylnitrite or other standard acid catalyzed N-nitrosation conditions. The resulting N-nitroso compounds are directly reduced to their corresponding hydrazines (2) by treatment with lithium aluminum hydride in a suitable solvent such as tetrahydrofuran. In step 2, hydrazines (2) are condensed by acid catalysis with 1-benzoylhexahydroazepine, which is available by the process described in J. Org. Chem., Vol. 33, pp 3187-95 (1968), or with benzyl 4-oxo-1-azepanecarboxylate, the synthesis of which is described in the experimental section. Fischer/Indole cyclization of the crude hydrazines provides the desired azepinoindoles (3). The Fischer/Indole cyclization can be effected with a variety of acids such as formic acid, acetic acid, trifluoroacetic acid, aqueous hydrochloric acid, aqueous sulfuric acid, or polyphosphoric acid.

Step 3 is effected by either catalytic hydrogenolysis when R2 is benzyl or benzyloxycarbonyl, or by base catalyzed hydrolysis in a suitable solvent such as

ethylene glycol when R2 is benzoyl. Azepinoindoles 4 (wherein when R2 is hydrogen) can conveniently be isolated as their hydrochloride salts.

It will be apparent to those skilled in the art that many of the requisite amines (1) are commercially available or known in the literature. The necessary 3,4-dihydro-1 (2H)-quinolinylamines required for Examples 1-13 are known compounds. Indolines required for the synthesis of Examples 14-18 are either commercially available or readily prepared from known indoles following the procedure described in Synthesis pp. 859-60 (1977). For the benzmorpholines and benzthiomorpholines required for Examples 19-25, the synthetic route shown in Figure 2 was followed. Nitrophenols 5 were alkylated with ethyl bromoacetate derivatives to afford 6. The nitro moiety is then reduced with Pd/C in the presence of hydrogen in a suitable solvent such as ethanol. In situ cyclization gives amide 7, which is then reduced with borane to provide the required amines 8.

Compounds of formula I can also be prepared by the reactions outlined in Figure 3. Azapinoindoles 9 are known in the literature (JMed Chem., 1968, I1,101-106) and can participate in a Michael conjugate addition into ethyl acrylate, or a derivative thereof, in the presence of a suitable base such as cesium carbonate. Base-catalyzed hydrolysis of esters 10 gives crude acids which then undergo intramolecular Friedel-Crafts acylation in an acidic media (e. g. polyphosphoric acid or Eaton's reagent). When R2 is benzoyl, azepinoindoles 12 can be obtained from base-catalyzed hydrolysis in tetrahydrofuran/methanol.

Aryl ketones 11 can be used as intermediates in the synthesis of additional compounds of formula I as shown in Figure 4. The ketone moiety is reduced with sodium borohydride to give alcohols 13. When R2 is benzoyl, base- catalyzed hydrolysis of alcohols 13 gives azepinoindoles 14. Alternatively, alcohols 13 can also be used as intermediates in the synthesis of additional compounds of formula I as shown in Figure 5. Alcohols 13 can be alkylated with an alkyl halide in the presence of sodium hydride or with phenols via Mitsunobu reaction

conditions. The use of thiols or amines in the Mitsunobu reaction can give additional derivatives. Removal of R2 gives azepinoindoles 16.

Azepinoindoles 9 can also be used to make compounds of formula I as shown in Figure 6. Alkylation of 9 with 2-bromomethyl-1,3-dioxolane, or a derivative thereof, gives compounds 17. Acid-catalyzed removal of the acetal group leads to an aldehyde that can be reacted with trimethylsulfoxonium iodide and sodium hydride to give epoxides 18. Use of a Lewis acid, such as boron trifluoride diethyl etherate, would lead to alcohols 19. These alcohols could be treated as above to give azepinoindoles 20 and 21.

In cases where compounds are sufficiently basic or acidic to form stable nontoxic acid or base salts, administration of the compounds as salts may be appropriate. Examples of pharmaceutically acceptable salts are organic acid addition salts formed with acids which form a physiological acceptable anion, for example, tosylate, methanesulfonate, acetate, citrate, malonate, tartarate, succinate, benzoate, ascorbate, a-ketoglutarate, and a-glycerophosphate. Suitable inorganic salts may also be formed, including hydrochloride, sulfate, nitrate, bicarbonate, and carbonate salts.

Pharmaceutically acceptable salts may be obtained using standard procedures well known in the art, for example by reacting a sufficiently basic compound such as an amine with a suitable acid affording a physiologically acceptable anion. Alkali metal (for example, sodium, potassium or lithium) or alkaline earth metal (for example calcium) salts of carboxylic acids can also be made.

Compounds of the present invention can conveniently be administered in a pharmaceutical composition containing the compound in combination with a suitable excipient. Such pharmaceutical compositions can be prepared by methods and contain excipients which are well known in the art. A generally recognized compendium of such methods and ingredients is

Remington's Pharmaceutical Sciences by E. W. Martin (Mark Publ. Co., 15th Ed., 1975). The compounds and compositions of the present invention can be administered parenterally (for example, by intravenous, intraperitoneal or intramuscular injection), topically, orally, or rectally.

For oral therapeutic administration, the active compound may be combined with one or more excipients and used in the form of ingestible tablets, buccal tablets, troches, capsules, elixirs, suspensions, syrups, wafers, and the like. Such compositions and preparations should contain at least 0.1% of active compound. The percentage of the compositions and preparations may, of course, be varied and may conveniently be between about 2 to about 60% of the weight of a given unit dosage form. The amount of active compound in such therapeutically useful compositions is such that an effective dosage level will be obtained.

The tablets, troches, pills, capsules, and the like may also contain the following: binders such as gum tragacanth, acacia, corn starch or gelatin; excipients such as dicalcium phosphate; a disintegrating agent such as corn starch, potato starch, alginic acid and the like; a lubricant such as magnesium stearate; and a sweetening agent such as sucrose, fructose, lactose or aspartame or a flavoring agent such as peppermint, oil of wintergreen, or cherry flavoring may be added. When the unit dosage form is a capsule, it may contain, in addition to materials of the above type, a liquid carrier, such as a vegetable oil or a polyethylene glycol. Various other materials may be present as coatings or to otherwise modify the physical form of the solid unit dosage form. For instance, tablets, pills, or capsules may be coated with gelatin, wax, shellac or sugar and the like. A syrup or elixir may contain the active compound, sucrose or fructose as a sweetening agent, methyl and propylparabens as preservatives, a dye and flavoring such as cherry or orange flavor. Of course, any material used in preparing any unit dosage form should be pharmaceutically acceptable and substantially non-toxic in the amounts employed. In addition, the active compound may be incorporated into sustained-release preparations and devices.

The compounds or compositions can also be administered intravenously or intraperitoneally by infusion or injection. Solutions of the active compound or its salts can be prepared in water, optionally mixed with a nontoxic surfactant. Dispersions can also be prepared in glycerol, liquid polyethylene glycols, triacetin, and mixtures thereof and in oils. Under ordinary conditions of storage and use, these preparations contain a preservative to prevent the growth of microorganisms.

Pharmaceutical dosage forms suitable for injection or infusion can include sterile aqueous solutions or dispersions or sterile powders comprising the active ingredient which are adapted for the extemporaneous preparation of sterile injectable or infusible solutions or dispersions, optionally encapsulated in liposomes. In all cases, the ultimate dosage form should be sterile, fluid and stable under the conditions of manufacture and storage. The liquid carrier or vehicle can be a solvent or liquid dispersion medium comprising, for example, water, ethanol, a polyol (for example, glycerol, propylene glycol, liquid polyethylene glycols, and the like), vegetable oils, nontoxic glyceryl esters, and suitable mixtures thereof. The proper fluidity can be maintained, for example, by the formation of liposomes, by the maintenance of the required particle size in the case of dispersions or by the use of surfactants. The prevention of the action of microorganisms can be brought about by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, thimerosal, and the like. In many cases, it will be preferable to include isotonic agents, for example, sugars, buffers or sodium chloride. Prolonged absorption of the injectable compositions can be brought about by the use in the compositions of agents delaying absorption, for example, aluminum monostearate and gelatin.

Sterile injectable solutions can be prepared by incorporating the active compound in the required amount in the appropriate solvent with various of the other ingredients enumerated above, as required, followed by filter sterilization. In the case of sterile powders for the preparation of sterile injectable solutions, the preferred methods of preparation are vacuum drying and

the freeze drying techniques, which yield a powder of the active ingredient plus any additional desired ingredient present in the previously sterile-filtered solutions.

For topical administration, the present compounds may be applied in pure form, i. e., when they are liquids. However, it will generally be desirable to administer them to the skin as compositions or formulations, in combination with a dermatologically acceptable carrier, which may be a solid or a liquid.

Useful solid carriers include finely divided solids such as talc, clay, microcrystalline cellulose, silica, alumina and the like. Useful liquid carriers include water, alcohols or glycols or water-alcohol/glycol blends, in which the present compounds can be dissolved or dispersed at effective levels, optionally with the aid of non-toxic surfactants. Adjuvants such as fragrances and additional antimicrobial agents can be added to optimize the properties for a given use. The resultant liquid compositions can be applied from absorbent pads, used to impregnate bandages and other dressings, or sprayed onto the affected area using pump-type or aerosol sprayers. Thickeners such as synthetic polymers, fatty acids, fatty acid salts and esters, fatty alcohols, modified celluloses or modified mineral materials can also be employed with liquid carriers to form spreadable pastes, gels, ointments, soaps, and the like, for application directly to the skin of the user.

Useful dosages of the compounds of formula I can be determined by comparing their in vitro activity, and in vivo activity in animal models.

Methods for the extrapolation of effective dosages in mice, and other animals, to humans are known to the art; for example, see U. S. Pat. No. 4,938,949.

The compound is conveniently administered in unit dosage form; for example, containing about 0.05 mg to about 500 mg, conveniently about 0.1 mg to about 250 mg, most conveniently, about 1 mg to about 150 mg of active ingredient per unit dosage form. The desired dose may conveniently be presented in a single dose or as divided doses administered at appropriate intervals, for example, as two, three, four or more sub-doses per day. The sub-

dose itself may be further divided, e. g., into a number of discrete loosely spaced administrations.

The compositions can conveniently be administered orally, sublingually, transdermally, or parenterally at dose levels of about 0.01 to about 150 mg/kg, preferably about 0.1 to about 50 mg/kg, and more preferably about 0.1 to about 10 mg/kg of mammal body weight.

For parenteral administration the compounds are presented in aqueous solution in a concentration of from about 0.1 to about 10%, more preferably about 0.1 to about 7%. The solution may contain other ingredients, such as emulsifiers, antioxidants or buffers.

The exact regimen for administration of the compounds and compositions disclosed herein will necessarily be dependent upon the needs of the individual subject being treated, the type of treatment and, of course, the judgment of the attending practitioner.

The ability of a compound of the invention to act as a 5-HT receptor agonist or antagonist can also be determined using in vitro and in vivo assays that are known in the art. The invention provides compounds of formula I that act as either agonists or as antagonists of one or more 5-HT receptor subtypes. The compounds Exemplified herein are 5-HT ligands, which typically displace >50% of a radiolabeled test ligand from one or more 5-HT receptor subtype at a concentration of 1 M. The procedures used for testing such displacement are well known and would be readily available to one skilled in the art.

DESCRIPTION OF PREFERRED EMBODIMENTS PREPARATION 1.

Preparation of 1-benzyl 4-ethyl 5-oxo-1,4-azepanedicarboxylate A dry 500 ml 3-neck flask was charged with benzyl 4-oxo-1-

piperidinecarboxylate (35.08 g, 150 mmol). It was dissolved in 130 ml Et2O and cooled to-45°C. Ethyldiazoacetate (20.5 ml, 195 mmol) and boron trifluoride ethyl ether (19.4 ml, 158 mmol) were added simultaneously by syringe pump over 45 minutes. The temperature was kept below-25°C. The reaction was stirred for 30 minutes longer, and then quenched with sat. NaHCO3. The ice bath was removed.

The reaction was diluted with EtOAc (250 ml) and H20 (150 ml). The layers were separated, and the organic phase was dried over MgSO4. It was concentrated under reduced pressure to an orange oil. The product was purified by flash chromatography (silica gel, 40% EtOAc/hexane), yielding product as pale yellow oil (42.1 g, 88%).'H NMR (CDC13) 8 3.96-3.83, 3.75-3.70,3.65,3.54-3.37,2.08-2.03,1.29-1.24; IR (liq.) 1743,1702,1476,1455, 1443,1425,1371,1318,1295,1238,1213,1178,1098,1068,1028 cm-'.

Preparation of benzyl 4-oxo-1-azepanecarboxylate A solution of potassium hydroxide (24.6 g, 375 mmol) in H2O (400 ml) was added to a solution of 1-benzyl 4-ethyl 5-oxo-1,4-azepanedicarboxylate (40.0 g, 125 mmol) in ethanol (400 ml). The resulting mixture was heated at reflux for 2.5 hours. Reaction was then cooled to rt., the ethanol was removed under reduced pressure, and was diluted with 200 ml brine and 300 ml ethyl acetate. The layers were separated, and the aqueous phase was extracted with ethyl acetate (2x 100 ml). The combined organic layers were washed with brine, dried over MgSO4, and concentrated to an orange oil in vacuo. The product was isolated by flash chromatography (silica gel, 40% EtOAc/hexane) yielding a clear, colorless oil (22.6 g, 73%).'H NMR (CDC13) 8 7.31-7.30,5.12,3.65-3.63,2.68-2.60,1.81-1.78; IR (liq.) 1698,1475,1454,1442,1423,1331,1320,1295,1270,1241,1191,1165, 1091,900,699 cm-'.

EXAMPLE 1 Preparation of 5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline hydrochloride

Step 1. Preparation of 3,4-dihydro-1 (2H)-quinolinylamine hydrochloride.

A neat reaction between 1,2,3,4-tetrahydroquinoline (3.71g, 27.9 mmol) and isoamylnitrite (8.72 g, 74.4 mmol) was allowed to stir for 1 hour.

The residual isoamylnitrite was removed under reduced pressure and the N- nitroso intermediate was taken up in tetrahydrofuran (20 ml). This solution was added dropwise to a refluxing solution of lithium aluminum hydride in tetrahydrofuran (55 ml, 1M, 55.0 mmol). One hour after the addition was complete, the reaction was cooled to 0 °C and quenched. The reaction was filtered, concentrated under reduced pressure, and extracted into ether. The ethereal solution was washed with water, brine and dried over anhydrous potassium carbonate. The resulting brown oil (4.11 g) was trapped as the hydrochloride salt and recrystallized from methanol\ethyl acetate\hexanes to provide the title compound (mp 186-189 °C).'H NMR (CDC13) 8 10.55,7.31, 7.10,6.98,6.87,3.59,2.74,2.05; IR (drift) 3053,2956,2940,2868,2841,2835,2724,2667,1603,1586,1580, 1567,1545,1499,747 cm~'.

Step 2. Preparation of benzyl l OH azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline-10-carboxylate.

A solution of 3, 4-dihydro-1 (2H)-quinolinylamine (2.97 g, 20.1 mmol), benzyl 4-oxo-1-azepanecarboxylate (4.96 g, 20.1 mmol), and glacial acetic acid (0.2 ml) in ethanol (200 ml) was allowed to reflux for 2.5 hours.

The reaction was then cooled and evaporated in vacuo. The hydrazone product was purified by flash chromatography (90g SiO2, 1 % MeOH/CH2Cl2) providing benzyl 4- [3, 4-dihydro-1 (2H)-quinolinylimino]-l-azepanecarboxylate (7.55 g) as an oil. To a solution of benzyl 4- [3, 4-dihydro-1 (2H)-quinolinylimino]-l- azepanecarboxylate (6. 79g, 17.99 mmol) in ethanol (200 ml) was added trifluoroacetic acid (6.22 g, 53.96 mmol). The reaction was heated and allowed to stir at reflux for 2.5 hours, at which time it was cooled to rt., evaporated, and extracted into dichloromethane. This extract was washed with water, brine, dried with anhydrous sodium sulfate, and evaporated under reduced pressure.

Crystallization from ethyl acetate/hexanes provided 2.93 g of the title compound (mp 131-133 °C).'H NMR (CDC13) 8 7.38,7.29,7.00,6.86,5.19,3.98,3.78, 2.97,2.24; IR (drift) 2947,1699,1473,1420,1358,1260,1250,1235,1216,1101,997, 764,757,746,703 cri'.

Step 3. Preparation of 5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline hydrochloride.

A mixture of benzyl l OH- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline-10-carboxylate (2.42 g, 6.71 mmol) and 10 % Pd/C (0.15 g) in ethanol (110 ml) was hydrogenated under 40 psi for 1.5 hours. The mixture was filtered through celite, rinsed with methanol, dichloromethane and evaporated. Methanolic hydrochloric acid is added and evaporated. The resulting product is recrystallized from methanol/ethyl acetate to give 1.40 g (80%) of the title compound (mp 261-263 °C).'H NMR (CD30D) 8 7.25,6.95,6.84,4.08,3.48,3.32,3.28,3.20,2.95,2.22; IR (drift) 2939,2894,

2880,2863,2832,2806,2759,2743,2687,2669,2645,2445,1332,1253, 743 cm~'.

EXAMPLE 2 Preparation of 2-methyl-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline hydrochloride Following the general procedure of Example 1, making non-critical variations but starting with 6-methyl-1,2,3,4-tetrahydroquinoline, the title compound was obtained (mp 268-270 °C).'H NMR (DMSO-d6) 8 9.6,6.99,6.61, 3.98,3.30,3.16,3.03,2.81,2.32,2.08; IR (drift) 2965,2949,2934,2902,2880, 2850,2823,2791,2769,2695,2659,2438,1458,1251,839 cm-'.

EXAMPLE 3 Preparation of 1-methoxy-5,6,9,10,11,12-hexahydro- 4H, 8H-azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline hydrochloride Following the general procedure of Example 1, making non-critical variations but starting with 7-methoxy-1,2,3,4-tetrahydroquinoline, the title

compound was obtained (mp 277-279 °C).'H NMR (DMSO-d6) 8 9.27,6.65,6. 32, 3.96,3.77,3.29,3.15,2.78,2.05; IR (drift) 2968,2953,2935,2889,2832,2803, 2780,2765,2744,2713,1594,1509,1247,1152,781 cari'.

EXAMPLE 4 Preparation of 2-fluoro-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline hydrochloride Following the general procedure of Example 1, making non-critical variations but starting with 6-fluoro-1,2,3,4-tetrahydroquinoline, the title compound was obtained (mp 273-276 °C).'H NMR (CD30D) 8 6.94,6.64,4.07,3.50,3.44, 3.32,3.28,3.15,2.94,2.22; IR (drift) 2957,2926,2894,2843,2814,2799,2742, 2708,2665,2561,2545,2440,1496,1419,1129 caf'.

EXAMPLE 5 Preparation of 6-methyl-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline hydrochloride Following the general procedure of Example 1, making non-critical variations but starting with 2-methyl-1,2,3,4-tetrahydroquinoline, the title compound is obtained (mp 214-217 °C).'H NMR (CDC13) 8 9.61,7.25,6.93,6.84,

4.62,3.32,3.11,2.87,2.12,2.01,1.20; IR (drift) 2968,2933,2893,2814,2742, 2711,2669,2560,2437,1463,1415,1377,1335,1324,742 cm-'.

EXAMPLE 6 Preparation of 5-methyl-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline hydrochloride Following the general procedure of Example 1, making non-critical variations but starting with 3-methyl-1,2,3,4-tetrahydroquinoline, the title compound was obtained (mp 273-274 °C).'H NMR (CDC13) 8 10.10,7.27,7.02, 6.88,4.07,3.51,3.37,3.31,3.00,2.65,2.37,1.20; IR (drift) 2956,2923,2899, 2867,2831,2800,2766,2686,2670,2562,2448,1454,1428,1257,740 cm-'.

EXAMPLE 7 Preparation of 4-methyl-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline hydrochloride Following the general procedure of Example 1, making non-critical variations but starting with 4-methyl-1,2,3,4-tetrahydroquinoline, the title compound was obtained (mp 260-263 °C).'H NMR (DMSO-d6) 8 9.79,7.22,6.92,

6.85,4.10,4.00,3.28,3.20,3.08,2.15,1.80,1.30; IR (drift) 2959,2939,2891, 2739,2709,2662,2647,2553,2542,2437,734 cm-'.

EXAMPLE 8 Preparation of (+)-6-methyl-5,6,9,10,11,12-hexahydro- 4H, 8H-azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline hydrochloride Following the general procedure of Example 5 making non-critical variations, preparative chiral HPLC was performed after step two on an EM ST 140R closed loop recycling prep HPLC system (EM Separations Technology). The column used was a 5x50 cm Chiralpak AD column at 30 °C. The mobile phase was 5% isopropanol/95% heptane at a flow rate of 75 ml/min. Peak collection was monitored by LTV detection at 285 nm. Following step three, the title compound was obtained (mp 196-199 °C).

EXAMPLE 9 Preparation of 4H, 8H-azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline hydrochloride

Following the general procedure of Example 5 making non-critical variations, preparative chiral HPLC was performed after step two on an EM ST 140R closed loop recycling prep HPLC system (EM Separations Technology). The column used was a 5x50 cm Chiralpak AD column at 30 °C. The mobile phase was 5% isopropanol/95% heptane at a flow rate of 75 ml/min. Peak collection was monitored by UV detection at 285 nm. Following step three, the title compound was obtained (mp 196-199 °C); [a] 25D =-27 (c 0.88, DMSO).

EXAMPLE 10 Preparation of (+)-5-methyl-5,6,9,10,11,12-hexahydro- 4H, 8H-azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline hydrochloride Following the general procedure of Example 6 making non-critical variations, preparative chiral HPLC was performed after step two on an EM ST 140R closed loop recycling prep HPLC system (EM Separations Technology). The

column used was a 5x50 cm Chiralpak AD column at 30 °C. The mobile phase was 5% isopropanol/95% heptane at a flow rate of 75 ml/min. Peak collection was monitored by UV detection at 285 nm. Following step three, the title compound was obtained (mp 259-262 °C); [a] 25D = + 20 (c 0.28, DMSO).

EXAMPLE 11 Preparation of (-)-5-methyl-5,6,9,10,11,12-hexahydro- 4H, 8H-azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline hydrochloride Following the general procedure of Example 6 making non-critical variations, preparative chiral HPLC was performed after step two on an EM ST 140R closed loop recycling prep HPLC system (EM Separations Technology). The column used was a 5x50 cm Chiralpak AD column at 30 °C. The mobile phase is 5% isopropanol/95% heptane at a flow rate of 75 ml/min. Peak collection was monitored by W detection at 285 nm. Following step three, the title compound was obtained (mp 259-262 °C); [afo =-21° (c 0.43, DMSO).

EXAMPLE 12 Preparation of (+)-4-methyl-5,6,9,10,11,12-hexahydro- 4H, 8H-azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline hydrochloride

Following the general procedure of Example 7 making non-critical variations, preparative chiral HPLC was performed after step two on an EM ST 140R closed loop recycling prep HPLC system (EM Separations Technology). The column used was a 5x50 cm Chiralpak AD column at 30 °C. The mobile phase was 5% isopropanol/95% heptane at a flow rate of 75 ml/min. Peak collection was monitored by UV detection at 285 nm. Following step three, the title compound was obtained (mp 261-263 °C); [a] 25D = +39 (c 0.41, chloroform).

EXAMPLE 13 Preparation of (-)-4-methyl-5,6,9,10,11,12-hexahydro- 4H, 8H-azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline hydrochloride

Following the general procedure of Example 7 making non-critical variations, preparative chiral HPLC was performed after step two on an EM ST 140R closed loop recycling prep HPLC system (EM Separations Technology). The column used was a 5x50 cm Chiralpak AD column at 30 °C. The mobile phase was

5% isopropanol/95% heptane at a flow rate of 75 ml/min. Peak collection was monitored by UV detection at 285 nm. Following step three, the title compound is obtained (mp 261-263 °C); [a] 25D =-39 (c 0.51, chloroform).

EXAMPLE 14 Preparation of 4,5,8,9,10,11-hexahydro-7H-azepino [4,5- b] pyrrolo [3,2,1-hi] indole hydrochloride Following the general procedure outlined in EXAMPLE 1, starting with indoline, and utilizing 1-benzoylhexahydoazepine as the ketone in step 4,5,7,8,10,11-hexahydro-9H-azepino [4,5-b] pyrrolo [3,2,1-hi] indol-9- yl (phenyl) methanone was obtained (mp 130-133 °C).'H NMR (CDC13) 87.42, 7.08,6.94,6.85,4.28,4.00,3.76,3.63,3.15,2.88; MS (ESI+) for C2lH20N2O H m/z 240.1 (M+H) +.

Step 4 A mixture of 4,5,7,8,10,11-hexahydro-9H-azepino [4,5- b] pyrrolo [3,2,1-hi] indol-9-yl (phenyl) methanone (1.0 g, 3.2 mmol) and potassium hydroxide (0.89 g, 15.8 mmol) in ethylene glycol (10 ml) was heated under N2at 170 °C for 3 h. The reaction was cooled to rt, poured into water (50 ml) and extracted with methylene chloride (4 x 50 ml). The combine organics were washed with brine, dried over anhydrous potassium carbonate, and concentrated in vacuo.

The residue was trapped as its HC1 salt by treatment of a solution of the product in methanol with ethereal HCI. The resulting precipitate is recrystallized from methanol and ethyl acetate to give the desired product (0.4 g) (mp 249-250 °C). 1H NMR (CDC13) 8 7.16,6.93,6.82,4.38,3.74,3.08,2.94; IR (drift) 2925,2916,2885, 2847,2805,1510,1462,1409,1350,1336,1306,1279,767,758,746 cm-'. EXAMPLE 15 Preparation of 2-fluoro-4,5,8,9,10,11-hexahydro-7H- azepino [4,5-b] pyrrolo [3,2,1-hi] indole hydrochloride

Following the general procedure outlined in EXAMPLE 14, and making non-critical variations but starting with 5-fluoro indoline, the title compound was obtained (mp 250-252 °C).'H NMR (CD30D) 8 6.68,6.43, 4.15,3.47,2.88,2.76; IR (drift) 2930,2911,1661,1507,1412,1354,1261, 1171,1112,938,857,848,839,708,688 cm-'.

EXAMPLE 16 Preparation of 2-methoxy-4,5,8,9,10, 11-hexahydro-7H- azepino [4,5-b] pyrrolo [3,2,1-hi] indole hydrochloride Following the general procedure outlined in EXAMPLE 14, and making non-critical variations but starting with 5-methoxy indoline, the title compound was obtained (mp 269-271 °C).'H NMR (CD30D) 8 6.70,6.57, 4.44,3.80,3.72,3.45,3.23,3.16; IR (drift) 2974,2948,2908,2891,2841,2817, 2805,2769,2718,1509,1421,1255,1244,1233,1142 cm-'.

EXAMPLE 17 Preparation of 5-methyl-4,5,8,9,10,11-hexahydro-7H- azepino [4,5-b] pyrrolo [3,2,1-hi] indole hydrochloride

Following the general procedure outlined in EXAMPLE 1, and making non-critical variations but starting with 2-methyl indoline, the title compound was obtained (mp 243-246 °C).'H NMR (CDC13) 8 7.13,6.91,7.80, 4.99-4.87,3.93,3.51-3.23,3.17,1.47; IR (drift) 2973,2960,2941,2927,2901, 2883,2848,2826,2794,2737,2650,2549,2438,1292,751 cm-'.

EXAMPLE 18 Preparation of 4,5-dimethyl-4,5,8,9,10,11-hexahydro-7H- azepino [4,5-b] pyrrolo [3,2,1-hi] indole hydrochloride Following the general procedure outlined in EXAMPLE 1, and making non-critical variations but starting with 2,3-dimethyl indole, the title compound was obtained (mp 195-197 °C).'H NMR (CD30D) 8 7.16,6.92, 6.81,4.40,3.64,3.53-3.35,3.16,1.54,1.43; IR (drift) 2866, 2847,2821,2727,2657,2635,2533,2427,1465,1372,1287,746 cm-'.

EXAMPLE 19 Preparation of 2,3,4,5,8b, 12a-decahydro-lH- azepino [4', 5' : 4,5] pyrrolo [3,2,1-jk] carbazole hydrochloride

Following the general procedure outlined in EXAMPLE 1, and making non-critical variations but starting with 1,2,3,4 tetramethyl carbazole, the title compound was obtained (mp 210-212 °C).'H NMR (CD30D) 8 7.16,6.94, 6.82,4.75,4.14,3.42,3.25,3.16,2.12-1.96,1.54,1.41,1.26,1.08; IR (drift) 3046,2936,2929,2846,2810,2744,2633,2541,2519,2429,1460,1328, 1290, 754,744 cm-'; EXAMPLE 20 Preparation of 6-methyl-1,2,8,9,10,11-hexahydro-7H- azepino [4,5-b] [1,4] oxazino [2,3,4-hi] indole hydrochloride Step 5. Preparation of 6-methyl-2H-1,4-benzoxazin-3 (4H)-one To a solution of 4-methyl-2-nitrophenol (9.95 g, 65.0 mmol) in acetone (170 ml) was added, in one portion, potassium carbonate (10.8 g, 78.0 mmol) and ethyl bromoacetate (7.9 ml, 71.5 mmol). The resulting mixture was heated at reflux for 3.5 hours. The acetone was removed in vacuo, and the resulting material was partitioned between ethyl acetate and water. The layers were separated, and the aqueous phase was extracted twice with ethyl acetate. The ethyl acetate layer was washed with saturated sodium bicarbonate, brine, dried over magnesium sulfate, filtered, and evaporated to afford an orange oil. The intermediate nitro compound was taken up in ethanol (150 ml) and hydrogenated with Pd/C (0.33 g) at 51 psi for 90 minutes. The mixture was filtered through celite, and the filtrate evaporated. The product was recrystallized from methanol to yield

7.29 g of the title compound as an off-white solid (mp 204-205 °C).'H NMR (DMSO-d6) 8 6.81-6.78,6.70-6.67,4.48,2.18; MS [MH-] 162.1.

Step 6. Preparation of 6-methyl-3,4-dihydro-2H-1,4-benzoxazine To a solution of 6-methyl-2H-1,4-benzoxazin-3 (4H)-one (7.02 g, 43.0 mmol) in tetrahydrofuran (130 ml) was added borane dimethylsulfide complex (43 ml, 10M). This solution was stirred at rt for 2.5 hours, then quenched with 1 M hydrochloric acid. The solvent was evaporated, and the residue was partitioned between saturated sodium bicarbonate and dichloromethane. The layers were separated, and the aqueous phase was extracted twice with dichloromethane. The dichloromethane layer was washed with brine, dried over magnesium sulfate, and evaporated to yield 5.1 g of the title compound as a pale yellow oil.'H NMR <BR> <BR> <BR> <BR> (CDC13) S 6.70-6.68,6.49-6.46,6.42,4.24-4.21,3.41-3.38,2.22; MS [w] 150.2.

Following the remainder of the general procedure of Example 1 (steps 1-3) and making non-critical variations but starting with 6-methyl-3,4- dihydro-2H-1,4-benzoxazine, the title compound was obtained (mp 271-273 °C).

'H NMR (CD30D) 8 6.59,6.40,4.44,4.17,3.52,3.49,3.27,3.24,2.57; IR (drift) 2979,2957,2934,2872,2855,2828,2792,2760,2746,2683,2652,1511, 1265,1243,1223 cm-'.

EXAMPLE 21 Preparation of 1,2,8,9,10,11-hexahydro-7H-azepino [4,5- b] [1,4] oxazino [2,3,4-hi] indole hydrochloride Following the general procedure of Example 20 but starting with 2

H-1,4-Benzoxazine-3 (4 H)-one, utilizing 1-benzoylhexahydoazepine as the ketone in the hydrazone formation of step two, and thus the deprotection sequence described in step 4 of example 14, the title compound was obtained (mp 217-219 °C).'H NMR (DMSO-d6) 8 9.6,7.01,6.85,6.50,4.46,4.18,3.28-3.08,2.50; IR (drift) 2949,2925,2878,2843,2812,2758,2689,2673,1499,1328,1247,1036, 872,771,729 cm-'.

EXAMPLE 22 Preparation of 6-chloro-1,2,8,9,10,11-hexahydro-7H- azepino [4,5-b] [1,4] oxazino [2,3,4-hi] indole hydrochloride Following the general procedure of Example 20 and making non- critical variations but starting with 2-amino-4-chlorophenol, the title compound was obtained (mp decompose >275°C).'H NMR (CD30D) b 6.84,6.50,4.49-4.48, 4.22-4.20,3.65-3.63,3.53-3.48,3.30-3.27; IR (free amine) (drift) 2932,2897,2882, 2823,1495,1466,1379,1355,1323,1277,1269,1236,1217,1199,1014 cm-'.

EXAMPLE 23 Preparation of 5-fluoro-1,2,8,9,10,11-hexahydro-7H- azepino [4,5-b] [1,4] oxazino [2,3,4-hi] indole hydrochloride

Following the general procedure of Example 20 and making non- critical variations but starting with 5-fluoro-2-nitrophenol, the title compound was obtained (mp decompose >250°C).'H NMR (CD30D) 8 6.76-6.72,6.38- 6.33,4.52-4.49,4.20-4.17,3.51-3.43,3.28-3.25,3.18-3.14; IR (drift) 2950, 2855,2805,2767,2757,2710,2675,2651,2565,2449,1645,1591,1500, 1333, 1109 cm-'.

EXAMPLE 24 Preparation of 5-methyl-1,2,8,9,10,11-hexahydro-7H- azepino [4,5-b] [1,4] oxazino [2,3,4-hi] indole hydrochloride Following the general procedure of Example 20 but starting from 5-methyl-2-nitrophenol and using glacial acetic acid for the cyclization in step 3, the title compound was obtained (mp 274-275 °C).'H NMR (CD30D) 8 6.81, 6.37,4.44,4.12,3.48-3.41,3.22,3.15,2.36; IR (drift) 2983,2965,2940,2880, 2856,2822,2809,2758,2731,2667,1590,1503,1331,1031,847 cl-'.

EXAMPLE 25 Preparation of 6-fluoro-1,2,8,9,10,11-hexahydro-7H- azepino [4,5-b] [1,4] oxazino [2,3,4-hi] indole hydrochloride Following the general procedure of Example 20 but starting from 4-

fluoro-2-nitrophenol and using p-toluene sulfonic acid for the cyclization in step 3, the title compound was obtained (mp 257-259°C).'H NMR (CD30D) 8 6.55-6.49, 6.43-6.40,4.44,4.17,3.49-3.44,3.38-3.33,3.26-3.23; IR (drift) 2949,2876,2845,2815,2768,2685,2676,2626,1511,1362,1277, 1224,1023,881,791 cm-'.

EXAMPLE 26 Preparation of 2-methyl-1,2,8,9,10,11-hexahydro-7H- azepino [4,5-b] [1,4] oxazino [2,3,4-hi] indole hydrochloride Following the general procedure of Example 20 and making non- critical variations but starting with 2-nitrophenol and ethyl-2-bromopropionate, the title compound was obtained (mp 255-257 °C).'H NMR (CD30D) 8 7.01,6.88, IR (drift) 2967,2931, 2809,2790,2736,2711,2655,2647,2557,2439,1502,1377,1322,1243, 794 cm EXAMPLE 27 Preparation of 1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] thiazino [2,3,4-hi] indole hydrochloride

Following the general procedure of Example 21 but starting from 2H-1,4-benzothiazin-3 (4H)-one and using 10% sulfuric acid for the cyclization in step 3, the title compound was obtained (mp 263 °C).'H NMR (CD30D) 8 7.24, 6.94,6.87,3.36-3.24,3.12-3.10; IR (drift) 2937,2929,2862,2814,2718,2663, 2626,2594,2544,2428,1463,1412,1335,782,739 cm~'.

EXAMPLE 28 Preparation of 8,9,10,11-hexahydro-7H- azepino [4,5-b] [1,4] oxazino [2,3,4-hi] indole hydrochloride Following the general procedure of Example 20 but starting with 2- nitrophenol and ethyl-2-bromoisobutyrate, and using p-toluene sulfonic acid for the cyclization in step 3, the title compound was obtained (mp decompose >260°C).

'H NMR (CD30D) 8 7.03,6.92,6.52,3.96,3.53-3.46,3.26-3.20,1.41; IR (drift) 2972,2948,2858,2824,2766,2751,1583,1498,1385,1332,1245,1202 cm-'.

EXAMPLE 29 Preparation of 4-fluoro-1,2,8,9,10,11-hexahydro-7H- azepino [4,5-b] [1,4] oxazino [2,3,4-hi] indole maleic acid Following the general procedure of Example 20 but starting with 2-fluoro-6-nitrophenol, using p-toluene sulfonic acid for the cyclization in step 3, and preparing the Maleic acid salt, the title compound was obtained (mp 176- 177°C).'H NMR (CD30D) å 6.95,6.78,6.24,4.51,4.19,3.42-3.50,3.23,3.16; IR (drift) 3009,2925,2899,2879,2835,2786,2714,1705,1626,1550,1531, 1526,1486,1358 cm''.

EXAMPLE 30 Preparation of 4-chloro-1,2,8,9,10,11-hexahydro-7H- azepino [4,5-b] [1,4] oxazino [2,3,4-hi] indole maleic acid Following the general procedure of Example 20 but starting with 6-chloro-2-nitrophenol, using p-toluene sulfonic acid for the cyclization in step 3, and preparing the Maleic acid salt, the title compound was obtained (mp 183- 184 °C).'H NMR (CD30D) 8 6.99,6.91,6.24,4.56,4.20,3.43-3.51,3.23, 3.16; IR (drift) 1645,1639,1627,1608,1568,1536,1517,1497,1476,1385, 1377,1372,1355,1196cl-'. EXAMPLE 31 Preparation of 5-chloro-1,2,8,9,10,11-hexahydro-7H- azepino [4,5-b] [1,4] oxazino [2,3,4-hi] indole maleic acid Following the general procedure of Example 20 but starting with 5- chloro-2-nitrophenol, using TFA in EtOH for the cyclization in step 3, and preparing the Maleic acid salt, the title compound was obtained (mp 177-179 °C).

'H NMR (CD30D) 8 7.05,6.55,6.24,4.50,4.18,3.42-3.50,3.23-3.25,3.14-3.16;

IR (drift) 2892,2867,2779,2745,1627,1569,1536,1491,1466,1451,1369, 1329,1024 cri'.

EXAMPLE 32 Preparation of 6- (trifluoromethyl)-1,2,8,9,10,11-hexahydro- 7H-azepino [4,5-b] [1,4] oxazino [2,3,4-hi] indole hydrochloride Following the general procedure of Example 20 but starting with 2- nitro-4- (trifluoro methyl)-phenol, using p-toluene sulfonic acid for the cyclization in step 3, the title compound was obtained (mp 248-250 °C).'H NMR (CD30D) 8 7.30,6.61,4.55,4.26,3.46-3.53; IR (drift) 2815,2797,2741,2670,2560,1583, 1333,1244,1198,1158,1107,1094,1060,1021 caf'. EXAMPLE 33 Preparation of 8,9,10,11-hexahydro-7H- azepino [4,5-b] [1,4] oxazino [2,3,4-hi] indole maleic acid Following the general procedure of Example 20 but starting with 4,5-difluoro-2-nitrophenol, using 10% sulfuric acid in step 3, and preparing the Maleic acid salt, the title compound was obtained (mp 184-185 °C).'H NMR (CD30D) 8 6.45,6.23,4.46,4.17,3.45-3.50,3.34-3.37,3.220-3.24; IR (drift) 3070,

2879,2780,2728,1601,1575,1518,1482,1457,1373,1353,1171,1042, 1000cm'.

EXAMPLE 34 Preparation of 5-chloro-6-fluoro-1,2,8,9,10,11-hexahydro- 7H-azepino [4,5-b] [1,4] oxazino [2,3,4-hi] indole maleic acid Following the general procedure of Example 20 but starting with 5- chloro-4-fluoro-2-nitrophenol, using 10% sulfuric acid in step 3, and preparing the Maleic acid salt, the title compound was obtained (mp 194-195 °C).'H NMR (CD30D) 8 6.52,6.24,4.46,4.18,3.51-3.45,3.29-3.37,3.21-3.25; IR (drift) 1615, 1583,1552,1501,1480,1456,1368,1355,1280,1222,1169 cri'. EXAMPLE 35 Preparation of 5-fluoro-6-chloro-1,2,8,9,10,11-hexahydro- 7H-azepino [4,5-b] [1,4] oxazino [2,3,4-hi] indole maleic acid Following the general procedure of Example 20 but starting with 4- chloro-5-fluoro-2-nitrophenol, using 10% sulfuric acid in step 3, and preparing the Maleic acid salt, the title compound was obtained (mp 173-175 °C). IH NMR (CD30D) 8 6.50,3.25,4.50,4.19,3.56-3.59,3.44-3.50,3.22-3.25; IR (drift) 3062, 3028,2971,2897,1626,1608,1585,1498,1463,1372,1365,1352,1153, 1036 crn~

EXAMPLE 36 Preparation of 8,9,10,11-hexahydro-7H- azepino [4,5-b] [1,4] oxazino [2,3,4-hi] indole maleic acid Following the general procedure of Example 20 but starting with 4,5-dichloro-2-nitrophenol, using 10% sulfuric acid in step 3, and preparing the Maleic acid salt, the title compound was obtained (mp 180-181 °C).'H NMR (CD30D) 8 6.68 (s, 1 H), 6.23 (s, 2 H), 4.49 (t, J= 4.4 Hz, 2 H), 4.20 (t, J= 4.8 Hz, 2 H), 3.59-3.62 (t, J= 2 Hz, H), 3.45-3.51 (m, 4 H), 3.22-3.26 (m, 2 H); IR (drift) 2887,2840,1625,1608,1578,1551,1486,1458,1372,1351,1273,1023 crn~l.

EXAMPLE 37 Preparation of 4, 6-dichloro-1,2,8,9,10,11-hexahydro-7H- azepino [4,5-b] [1,4] oxazino [2,3,4-hi] indole hydrochloride Following the general procedure of Example 20 but starting with 3,5-dichloro-2-nitrophenol, and using 10% sulfuric acid in step 3, the title compound was obtained (decompose >255°C).'H NMR (CD30D) 8 6.89,4.55, 4.21,3.56-3.59,3.44-3.51,3.23-3.27; IR (drift) 2955,2895,2743,2652,2635, 2556,2428,1494,1468,1420,1345,1294,1229 cm-1.

EXAMPLE 38 Preparation of 1-chloro-2-fluoro-4,5,8,9,10,11-hexahydro- 7H-azepino [4,5-b] pyrrolo [3,2,1-hi] indole maleic acid

Following the general procedure outlined in EXAMPLE 14, and making non-critical variations but starting with 6-chloro-5-fluoro indoline, the title compound was obtained (amorphous solid).'H NMR (CD30D) 6.70,6.23, 4.52,3.69,3.34-3.22,3.08; IR (drift) 2420 (b), 1628,1561,1506 (s), 1449, 1421,1378 (s), MS (ESI+) for Cl4HI4CIFN2 m/z 265.2 (M+H) +.

EXAMPLE 39 Preparation of 2-chloro-4,5,8,9,10, 11-hexahydro-7H- azepino [4,5-b] pyrrolo [3,2,1-hi] indole maleic acid Following the general procedure outlined in EXAMPLE 14, and making non-critical variations but starting with 5-chloro-indoline, the title compound was obtained (amorphous solid).'H NMR (CD30D) 7.16,6.91,6.81, MS (ESI+) for Cl4HlsclN2 m/z 247.2 (M+H) +.

EXAMPLE 40 Preparation of 1-chloro-4, 5,8,9,10, 11-hexahydro-7H- azepino [4,5-b] pyrrolo [3,2,1-hi] indole maleic acid

Following the general procedure outlined in EXAMPLE 14, and making non-critical variations but starting with 6-chloro-indoline, the title compound was obtained (amorphous solid).'H NMR (CD30D) 6.91,6.81,6.77, MS (ESI+) for Cl4HlsclN2 m/z 247.2 (M+H) +.

EXAMPLE 41 Preparation of 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-4-one oxalate.

Step 7. Preparation of ethyl 3- (3-benzoyl-2,3,4,5-tetrahydroazepino [4,5- b] indol-6 (lH)-yl) propanoate.

A mixture of 3-benzoyl-1,2,3,4,5,6-hexahydroazepino [4,5- b] indole (5.00 g, 17.2 mmol), cesium carbonate (5.61 g, 17.2 mmol), and ethyl acrylate (1.90 mL, 17.5 mmol) in acetonitrile (250 mL) was heated under N2at 50 °C for 5 h (reaction can also be run in DMF at room temperature). Cooled to room temperature, diluted with H20, and extracted with EtOAc. The combined organic extracts were washed with saturated aqueous NaCl, dried over Na2SO4, decanted, and concentrated under reduced pressure. The crude product was purified by silica gel chromatography with EtOAc/hexanes (2: 1) to give 4.82 g (72%) of the title compound as a yellow oil. 'H NMR (CDCl3) 8 7.57- 7.38, 7.32,7.23-7.07,4.49-4.33,4.20-4.02,3.77-3.66,3.28-3.13,2.94, 2.72,1.24 ; IR (liq.) 2981,1731,1631,1467,1445,1422,1381,1368,1349,1319,1295,1272,

1242,1187,742,707 cnl-'; MS (ESI) 391.0 (M++H).

Step 8. Preparation of 10-benzoyl-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-4- one.

A solution of potassium hydroxide (0.80 g, 14.3 mmol) in H, O (20 mL) was added to a solution of ethyl 3- (3-benzoyl-2,3,4,5- tetrahydroazepino [4,5-b] indol-6 (1H)-yl) propanoate (4.25 g, 10.9 mmol) in THF (30 mL). The reaction mixture was heated at 60 °C for 1 h, then cooled to room temperature, acidified with 10% aqueous HCI, and extracted with EtOAc. The combined organic extracts were washed with saturated aqueous NaCI, dried over Na2SO4, decanted, and concentrated under reduced pressure to give 3.73 g of crude acid. The crude acid (2.00 g, 5.52 mmol) was then added to neat PPA (18.6 g) stirring at 100 °C under N2. After 1.5 h, the reaction was cooled to room temperature, quenched with ice and 10% aqueous NaOH, and then extracted with EtOAc. The combined organic extracts were washed with saturated aqueous NaCI, dried over Na2SO4, decanted, and concentrated under reduced pressure.

The crude product was purified by silica gel chromatography with EtOAc/hexanes (gradient 1: 1 to 2: 1) to give 0.81 g (43%) of the title compound as a yellow solid (mp 177.5-181 °C). 1H NMR (d-DMSO) 8 7.75,7.46,7.09, IR (drift) 1676,1628,1587,1493, 1483,1466,1428,1357,1324,1295,1276,1266,1191,754,706 cm~l.

Step 9. Preparation of 5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-4-one oxalate.

A solution of 10-benzoyl-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-4- one (0.20 g, 0.58 mmol) in THF/ MeOH/50% aqueous NaOH (3: 2: 1,9 mL) was heated under N2 at reflux for 4 d.

Cooled to room temperature, diluted with saturated aqueous NaCI, and extracted with CH2Cl2. The combined organic extracts were washed with saturated aqueous NaCI, dried over Na2SO4, decanted, and concentrated under reduced pressure. The crude product was purified by silica gel chromatography with CH2Cl2/MeOH/Et2NH (gradient 95: 5: 0 to 95: 4: 1) to give 0.10 g (74%) of the free base of title compound as a dark yellow foam. The oxalate salt was prepared by treating a solution of the free base in methanol with a solution of oxalic acid in ether to give a precipitate that crystallized from methanol as small yellow needles of the title compound (mp 199-202 °C [dec.]).'H NMR (d- DMSO) 8 7.78,7.46,7.15,4.39,4.19,3.39,3.34,3.24,3.14,3.02; IR (drift) 2965,2890,2841,2799,2732,2516,2484,1720,1673,1626,1607,1591, 1492, 1460,1206 cni'.

EXAMPLE 42 Preparation of 2-fluoro-5,6,9,10,11, 12-hexahydro4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-4-one maleate.

Following the general procedure of Example 41, making non-critical variations but starting with 3-benzoyl-9-fluoro-1,2,3,4,5,6-hexahydroazepino [4,5- b] indole and using maleic acid for the salt formation, the title compound was obtained (mp 242-244 °C [dec.]).'H NMR (d-DMSO) 8 9.18,7.67,7.21,4.40, 3.33,3.25,3.12,3.04; IR (drift) 3358,2970,2959,2830,2792,2785,2752,1681, 1593,1490,1464,1383,1330,1216,907 cri'.

EXAMPLE 43 Preparation of 2-chloro-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-4-one oxalate.

Following the general procedure of Example 41, making non-critical variations but starting with 3-benzoyl-9-chloro-1,2,3,4,5,6-hexahydroazepino [4,5- indole, the title compound was obtained (mp 236.5-238 °C [dec.]).'H NMR (d- DMSO) 8 7.89,7.38,4.41,3.69,3.38,3.33,3.23,3.13,3.04; IR (mull) 3440,2644, 2514,1915,1686,1491,1420,1327,1318,1251,1138,1094,1030,914,7 20 cm~l.

EXAMPLE 44 Preparation of 6-methyl-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-4-one oxalate.

Following the general procedure of Example 41, making non- critical variations but using ethyl crotonate in step 7, the title compound was obtained (mp 215-215.5 °C).'H NMR (d-DMSO) 8 7.79,7.47,4.97,3.50-3.20, 3.15,2.73,1.16; IR (drift) 3020,2984,2969,1727,1684,1609,1589, 1471, 1327,1217,1194,1178,1100,752,706 crri'.

EXAMPLE 45 Preparation of 2-fluoro-6-methyl-5,6,9,10,11,12- hexahydro-4H, 8H-azepino [4', 5' : 4,5] pyrrolo [3,2,1- ij] quinolin-4-one oxalate.

Following the general procedure of Example 41, making non- critical variations but starting with 3-benzoyl-9-fluoro-1,2,3,4,5,6- hexahydroazepino [4,5-b] indole and using ethyl crotonate in step 7, the title compound was obtained (mp 209.5-211.5 °C).'H NMR (d-DMSO) 8 7.69,7.22, 4.99,3.44-3.22,3.12,2.78,1.16; IR (drift) 2969,1743,1727,1716,1688,1646, 1616,1480,1418,1377,1214,1145,1102,858,602 cari'.

EXAMPLE 46 Preparation of 2,3-dichloro-6-methyl-5,6,9,10,11,12- hexahydro-4H, 8H-azepino [4', 5' : 4,5] pyrrolo [3,2,1- ij] quinolin-4-one mesylate.

Following the general procedure of Example 41, making non- critical variations but starting with 3,4,5,6- hexahydroazepino [4,5-b] indole, using ethyl crotonate in step 7, and using methanesulfonic acid for the salt formation, the title compound was obtained (mp 225-230 °C [dec.]). lH NMR (d-DMSO) 6 8.94,8.12,4.97,3.48-3.20,3.13, 2.77,2.30,1.20; IR (drift) 3029,2979,2849,2792,1683,1481,1410,1312, 1214,1196,1184,1161,1145,1040,775 cm-'.

EXAMPLE 47 Preparation of 6-propyl-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-4-one hydrochloride.

Following the general procedure of Example 41, making non- critical variations but using ethyl trans-hexenoate in step 7 and using hydrochloric acid for the salt formation, the title compound was obtained (mp 7.79,7.45,7.14,4.87,3.54,3.45- 3.19,3.16,2.83,1.47,1.13,0.78; IR (drift) 2957,2926,2870,2853,2741,1683, 1588,1471,1416,1354,1325,1279,1191,795,751 cari'.

EXAMPLE 48 Preparation of 6- (trifluoromethyl)-5,6,9,10,11,12- hexahydro-4H, 8H-azepino [4', 5' : 4,5] pyrrolo [3,2,1- ij] quinolin-4-one oxalate.

Following the general procedure of Example 41, making non- critical variations but using ethyl 4,4,4-trifluorocrotonate in step 7 and using hydrochloric acid for the salt formation, the title compound was obtained (mp 201.5-202.5 °C).'H NMR (d-DMSO) 8 7.86,7.54,7.24,5.94,3.73,3.67,3.43- 3.19,3.16,3.00; IR (drift) 1726,1694,1645,1639,1592,1469,1416,1336, 1272,1253,1204,1195,1177,1127,945 cmi'.

EXAMPLE 49 Preparation of 12a-octahydro-4H, 7aH- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-4-ol

Step 10 Preparation of 10-benzoyl-5,6,8,9,10,11,12,12a-octahydro-

4H, 7aH-azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-4-ol.

A solution of 10-benzoyl-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-4- one (1.46 g, 4.24 mmol) in ethanol (40mL) was cooled to 0 °C under N2. Added sodium borohydride (0. 32 g, 8.46 mmol) and allowed to warm slowly to room temperature. Concentrated under reduced pressure to approximately 10 mL, diluted with H2O, and extracted with CH2Cl2. The combined organic extracts were washed with saturated aqueous NaCl, dried over Na2SO4, decanted, and concentrated under reduced pressure. The crude product was purified by silica gel chromatography with EtOAc/heptanes (2: 1) to give 1.24 g (84%) of the title compound as a yellow foam.'H NMR (CDC13) 8 7.42,7.33,7.12-7.02,5.10,4.13,4.02,3.68,3.21, 2.92,2.38,2.23,1.80; IR (drift) 1627,1614,1475,1466,1457,1448,1429, 1372,1360,1329,1292,1268,785,747,706 cri'; MS (ESI) 369.1 (M+Na).

The 10-benzoyl-5,6,8,9,10,11,12,12a-octahydro-4H, 7aH- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-4-ol was then hydrolyzed following the procedure outlined in step 9 to give 12a-octahydro-4H, 7aH- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-4-ol as a tan foam.'HNMR (CDC13) 8 7.43,7.09,5.11,4.11,3.16,3.02,2.38,2.26; IR (drift) 3300,3047,2923,2878, 2828,2751,1479,1454,1430,1415,1371,1330,1199,1074,746 cmi'; HRMS (EI) calcd for Cl5Hl8N2O 242.1419, found 242.1422.

EXAMPLE 50 Preparation of 4-methoxy-5,6,8,9,10,11,12,12a-octahydro- 4H, 7aH-azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline

Step 11. Preparation of 10-benzoyl-4-methoxy-5,6,8,9,10,11,12,12a- octahydro-4H, 7aH-azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline.

NaH (60% dispersion in mineral oil, 0.50g, 1.2 mmol) was added to a solution of 10-benzoyl-5,6,8,9,10,11,12,12a-octahydro-4H, 7aH- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-4-ol (0.20 g, 0.58 mmol) in DMF (5.0 mL) at 0 °C under N2. After 30 min, iodomethane (0.040 mL, 0.64 mmol) was added. The reaction was quenched with saturated aqueous NH4C1 after 1 h and then allowed to warm to room temperature prior to extracting with EtOAc. The combined organic extracts were washed with saturated aqueous NaCI, dried over Na2SO4, decanted, and concentrated under reduced pressure. The crude product was purified by silica gel chromatography with EtOAc/heptanes (2: 1) to give 0.16 g (79%) of the title compound as a beige foam.'H NMR (CDC13) 8 7.46- 7.30,6.94,4.51,4.22-4.03,4.01-3.79,3.65-3.41,3.29,3.12,3.04, 2.90,2.82, 2.34,2.08; IR (drift) 1631,1493,1477,1459,1422,1370,1359,1324,1292, 1267,1098,1085,786,748,706 cm'' ; HRMS (FAB) calcd for C23H24N202+H 361.1916, found 361.1913.

Following the general procedure of step 4, making non-critical variations but starting with 12a- octahydro-4H, 7aH-azepino [4', 5': 4,5] pyrrolo [3,2,1-ij] quinoline, the title compound was obtained as a brown oil.'H NMR (CDC13) å 7.45,7.07,4.56, 4.26,4.09,3.42,3.27-3.13,3.11-2.94,2.49,2.18; IR (liq.) 2926,2905,2882, 2820,1492,1479,1453,1415,1370,1332,1200,1098,1083,1066,748 cm~l, HRMS (FAB) calcd for C, 6H2N20+H 257.1654, found 257.1665.

EXAMPLE 51 Preparation of 4-phenoxy-5,6,9,10,11,12-hexahydro- 4H, 8H-azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline

Step 12. Preparation of 10-benzoyl-4-phenoxy-5,6,9,10,11,12-hexahydro- 4H, 8H-azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline 1,1'-Azobis (N, N-dimethylformamide) (0.34 g, 2.0 mmol) was added to a solution of 10-benzoyl-5,6,8,9,10,11,12,12a-octahydro-4H, 7aH- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-4-ol (0.45 g, 1.3 mmol), phenol (0.18 g, 1.9 mmol), and tributylphosphine (0.49 mL, 2.0 mmol) in dry benzene (4.0 mL) at room temperature under N2. The reaction mixture immediately congealed but resumed stirring upon heating to 60 °C. After 5 h, the reaction was cooled to room temperature and filtered to remove white precipitate. The filtrate was concentrated under reduced pressure and purified by silica gel chromatography with heptanes/EtOAc (gradient 3: 1 to 3: 2) to give 0.26 g (47%) of the title compound as a beige foam.'H NMR (CDC13) 8 32,7.11-6.95,5.68, 4.21-3.90,3.69,3.21,2.91,2.63,2.34; IR (drift) 1630,1596,1492,1458,1421, 1359,1327,1291,1267,1226,1192,786,750,706,694 cmi'; MS (ESI) 423.3 (M++H).

Following the general procedure of step 4, making non-critical variations but starting with 10-benzoyl-4-phenoxy-5,6,9,10,11,12-hexahydro- 4H, 8H-azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline, the title compound was obtained. MS (ESI) 319.2 (M++H).

EXAMPLE 52 Using synthetic procedures similar to those described herein, the following compounds of formula (I) wherein R2 is hydrogen can also be prepared:

4-bromo-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] oxazino [2,3,4- hi] indole (100); 5-bromo-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] oxazino [2,3,4- hi] indole (101); 6-bromo-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] oxazino [2,3,4- hi] indole (102); 5,6-dibromo-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] oxazino [2,3,4- hi] indole (103); 4,6-dibromo-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] oxazino [2,3,4- hi] indole (104); 4-methoxy-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] oxazino [2,3,4- hi] indole (105); 5-methoxy-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] oxazino [2,3,4- hi] indole (106); 6-methoxy-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] oxazino [2,3,4- hi] indole (107); 4-(triflouromethyl)-1,(triflouromethyl)-1, 2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] oxazino [2,3,4-hi] indole (108); 5- (triflouromethyl)-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] oxazino [2,3,4-hi] indole (109); 4-benzyloxy-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] oxazino [2,3,4- hi] indole (110); 5-benzyloxy-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] oxazino [2,3,4- hi] indole (111); 6-benzyloxy-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] oxazino [2,3,4- hi] indole (112);

4-fluoro-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] thiazino [2,3,4- hi] indole (113); 5-fluoro-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] thiazino [2,3,4- hi] indole (114); 6-fluoro-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] thiazino [2,3,4- hi] indole (115); 4-chloro-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] thiazino [2,3,4- hi] indole (116); 5-chloro-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] thiazino [2,3,4- hi] indole (117); 6-chloro-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] thiazino [2,3,4- hi] indole (118); 4,5-difluoro-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] thiazino [2,3,4- hi] indole (119); 8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] thiazino [2,3,4- hi] indole (120); 8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] thiazino [2,3,4- hi] indole (121); 4-chloro-5-fluoro-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] thiazino [2,3,4-hi] indole (122); 4-chloro-6-fluoro-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] thiazino [2,3,4-hi] indole (123); 5-chloro-6-fluoro-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] thiazino [2,3,4-hi] indole (124); 6-chloro-5-fluoro-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] thiazino [2,3,4-hi] indole (125);

4-methyl-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] thiazino [2,3,4- hi] indole (126); 5-methyl-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] thiazino [2,3,4- hi] indole (127); 6-methyl-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] thiazino [2,3,4- hi] indole (128); 4-methoxy-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] thiazino [2,3,4- hi] indole (129); 5-methoxy-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1, 4] thiazino [2,3,4- hi] indole (130); 6-methoxy-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1, 4] thiazino [2,3,4- hi] indole; (131) 4-(triflouromethyl)-1,(triflouromethyl)-1, 2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] thiazino [2,3,4-hi] indole (132); 5-(triflouromethyl)-1,(triflouromethyl)-1, 2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] thiazino [2,3,4-hi] indole (133); 6- (triflouromethyl)-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] thiazino [2,3,4-hi] indole (134); 4-benzyloxy-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1, 4] thiazino [2,3,4- hi] indole (135); 5-benzyloxy-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] thiazino [2,3,4- hi] indole (136); 6-benzyloxy-1,2,8,9,10,11-hexahydro-7H-azepino [4,5-b] [1,4] thiazino [2,3,4- hi] indole (137); 1-fluoro-4,5,8,9,10,11-hexahydro-7H-azepino [4,5-b] pyrrolo [3,2,1-hi] indole (138);

3-fluoro-4,5,8,9,10,11-hexahydro-7H-azepino [4,5-b] pyrrolo [3,2,1-hi] indole (139); 1-bromo-4,5,8,9,10, 11-hexahydro-7H-azepino [4,5-b] pyrrolo [3,2,1-hi] indole (140); 2-bromo-4,5,8,9,10, 11-hexahydro-7H-azepino [4,5-b] pyrrolo [3,2,1-hi] indole (141); 3-bromo-4,5,8,9,10,11-hexahydro-7H-azepino [4,5-b] pyrrolo [3,2,1-hi] indole (142); 3-chloro-1-4,5,8,9,10,11-hexahydro-7H-azepino [4,5-b] pyrrolo [3,2,1-hi] indole (143); 2-chloro-1-fluoro-4,5,8,9,10,11-hexahydro-7H-azepino [4,5-b] pyrrolo [3,2,1- hi] indole (144); 1-methoxy-4,5,8,9,10,11-hexahydro-7H-azepino [4,5-b] pyrrolo [3,2,1-hi] indole (145); 3-methoxy-4,5,8,9,10,11-hexahydro-7H-azepino [4,5-b] pyrrolo [3,2,1-hi] indole (146); 4-methyl-4,5,8,9,10, 11-hexahydro-7H-azepino [4,5-b] pyrrolo [3,2; 1-hi] indole (147); 1- (trifluoromethyl)-4,5,8,9,10,11-hexahydro-7H-azepino [4,5-b] pyrrolo [3,2,1- hi] indole (148); 2- (trifluoromethyl)-4, 5,8,9,10, 11-hexahydro-7H-azepino [4,5-b] pyrrolo [3,2,1- hi] indole (149); 3- (trifluoromethyl)-4,5,8,9,10,11-hexahydro-7H-azepino [4,5-b] pyrrolo [3,2,1- hi] indole (150); 12a-octahydro-4H, 7aH- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (151);

4- (3-chlorophenoxy)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (152); 4- (2-chlorophenoxy)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (153); 4- (4-methoxyphenoxy)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (154); 4- (3-methoxyphenoxy)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (155); 4- (2-methoxyphenoxy)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (156); 4- (4-bromo-2-methoxyphenoxy)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (157); 8H-azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-4- amine (158); 8H-azepino [4', 5' : 4,5] pyrrolo [3,2,1- ij] quinolin-4-amine (159); N- (4-chlorophenyl)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-4-amine (160); N- (3-chlorophenyl)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-4-amine (161); N- (2-chlorophenyl)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-4-amine (162); N- (4-methoxyphenyl)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-4-amine (163); N- (3-methoxyphenyl)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-4-amine (164);

N- (2-methoxyphenyl)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-4-amine (165); N- (4-bromo-2-methoxyphenyl)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-4-amine (166); 5,6,9,10,11,12-hexahydro-4H, 8H-azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline-4- thione (167); 4- (phenylsulfonyl)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (168); 4- (4-chlorophenylsulfonyl)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (169); 4- (3-chlorophenylsulfonyl)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (170); 4- (2-chlorophenylsulfonyl)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (171); 4- (4-methoxyphenylsulfonyl)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (172); 4- (3-methoxyphenylsulfonyl)-5,6,9,10,11,12-hexahydro-4H, 8H-' azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (173); 4- (2-methoxyphenylsulfonyl)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (174); 4- (4-bromo-2-methoxyphenylsulfonyl)-5,6,9,10,11,12-hexahydro-4 H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (175); 12a-octahydro-4H, 7aH-azepino [4', 5' : 4,5] pyrrolo [3,2,1- ij] quinolin-5-ol (176); 5-methoxy-5,6,8,9,10,11,12,12a-octahydro-4H, 7aH- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (177);

5-benzyloxy-5,6,8,9,10,11,12,12a-octahydro-4H, 7aH- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (178); 5-phenoxy-5,6,9,10,11,12-hexahydro-4H, 8H-azepino [4', 5' : 4,5] pyrrolo [3,2,1- ij] quinoline (179); 5- (4-chlorophenoxy)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (180); 5- (3-chlorophenoxy)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (181); 5- (2-chlorophenoxy)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (182); 5- (4-methoxyphenoxy)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (183); 5- (3-methoxyphenoxy)-5,6,9,10, 11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (184); 5- (2-methoxyphenoxy)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (185); 5- (4-bromo-2-methoxyphenoxy)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (186); 8H-azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-5- amine (187); N-phenyl-5,6,9,10,11,12-hexahydro-4H, 8H-azepino [4', 5' : 4,5] pyrrolo [3,2,1- ij] quinolin-5-amine (188); N- (4-chlorophenyl)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-5-amine (189); N- (3-chlorophenyl)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-5-amine (190);

N- (2-chlorophenyl)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-5-amine (191); N- (4-methoxyphenyl)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-5-amine (192); N- (3-methoxyphenyl)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-5-amine (193); N- (2-methoxyphenyl)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-5-amine (194); N- (4-bromo-2-methoxyphenyl)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-5-amine (195); 8H-azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline-5- thione (196); 5- (phenylsulfonyl)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (197); 5- (4-chlorophenylsulfonyl)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (198); 5- (3-chlorophenylsulfonyl)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (199); 5- (2-chlorophenylsulfonyl)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (200); 5- (4-methoxyphenylsulfonyl)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (201); 5- (3-methoxyphenylsulfonyl)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (202); 5- (2-methoxyphenylsulfonyl)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (203);

5- (4-bromo-2-methoxyphenylsulfonyl)-5,6,9,10,11,12-hexahydro-4 H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (204); 4- (4-chlorophenoxy)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (205); 1- [2- (4-fluorophenoxy) 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (206); 1- [2- (3-fluorophenoxy) 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (207); 1- [2- (2-fluorophenoxy) ethoxy]-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (208); 1- [2- (4-chlorophenoxy) 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (209); 1- [2- (3-chlorophenoxy) ethoxy]-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (210); 1- [2- (2-chlorophenoxy) ethoxy]-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (211); 1- [2- (4-bromophenoxy) ethoxy]-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (212); 1- [2- (3-bromophenoxy) ethoxy]-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (213); 1- [2- (2-bromophenoxy) ethoxy]-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (214); 1- [2- (4-methoxyphenoxy) ethoxy]-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (215); 1- [2- (3-methoxyphenoxy) 12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (216);

1- [2- (2-methoxyphenoxy) ethoxy]-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (217); 1- [2- (4-methylphenoxy) ethoxy]-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (218) ; 1- [2- (3-methylphenoxy) ethoxy]-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (219); 1- [2- (2-methylphenoxy) ethoxy]-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (220); 1-[2-(1-naphthyloxy)[2-(1-naphthyloxy) ethoxy]-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (221); 1- [2- (2-naphthyloxy) ethoxy]-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (222); 1- [2- ( [ 1,1'-biphenyl]-4-yloxy) ethoxy]-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (223); 1-[2-([1, 1'-biphenyl]-3-yloxy)[2-([1, 1'-biphenyl]-3-yloxy) 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (224); 1- [2- ( [ 1,1'-biphenyl]-2-yloxy) ethoxy]-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (225); 1- {2- [4- (trifluoromethoxy) phenoxy] ethoxy}-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (226); 1- {2- [3- (trifluoromethoxy) phenoxy] ethoxy}-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (227); 1- {2- [2- (trifluoromethoxy) phenoxy] ethoxy}-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (228); 1- {2- [4- (trifluoromethyl) phenoxy] ethoxy}-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (229);

1- {2- [3- (trifluoromethyl) phenoxy] ethoxy}-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (230); and 1- {2- [2- (trifluoromethyl) phenoxy] ethoxy}-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline (231).

EXAMPLE 53 Using synthetic procedures similar to those described herein, the following compounds of formula (I) wherein R2 is a protecting group can also be prepared: benzyl 5,6,8,9,11,12-hexahydro-4H, 10H-azepino [4', 5' : 4,5] pyrrolo [3,2,1- ij] quinoline-10-carboxylate; benzyl l OH- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline-10-carboxylate; 10-benzoyl-1-methoxy-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5': 4,5] pyrrolo- [3,2,1-ij] quinoline; benzyl 2-fluoro-5,6,8,9,11,12-hexahydro-4H, 10H- azepino [4', 5': 4,5] pyrrolo [3,2,1-ij] quinoline-10-carboxylate; benzyl 10H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline-10-carboxylate; benzyl 5-methyl-5,6,8,9,11, 12-hexahydro-4HslOH- azepino [4', 5' : 4, 5] pyrrolo [3,2,1-ij] quinoline-10-carboxylate; benzyl 10H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline-10-carboxylate; (+)-benzyl 6-methyl-5,6,8,9,11, 12-hexahydro-4H, 1 OH- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline-10-carboxylate; (-)-benzyl 10H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline-10-carboxylate; (+)-benzyl 1 OH- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline-10-carboxylate;

(-)-benzyl 5-methyl-5,6,8,9,11, 12-hexahydro-4H, 1 OH- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline-10-carboxylate; (+)-benzyl l OH- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline-10-carboxylate; (-)-benzyl 1 OH- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline-10-carboxylate; benzyl 2-methyl-1,2,7,8,10,11-hexahydro-9H-azepino [4,5-b] [1,4] oxazino [2,3,4- hi] indole-9-carboxylate; benzyl 7,8,10,11-hexahydro-9H-azepino [4,5- b] [1,4] oxazino [2,3,4-hi] indole-9-carboxylate; benzyl 4-fluoro-1,2,7,8,10,11-hexahydro-9H-azepino [4,5-b] [1,4] oxazino [2,3,4- hi] indole-9-carboxylate; benzyl 4-chloro-1,2,7,8,10,11-hexahydro-9H-azepino [4,5-b] [1,4] oxazino [2,3,4- hi] indole-9-carboxylate; benzyl 5-fluoro-1,2,7,8,10,11-hexahydro-9H-azepino [4,5-b] [1,4] oxazino [2,3,4- hi] indole-9-carboxylate; benzyl 5-chloro-1,2,7,8,10,11-hexahydro-9H-azepino [4,5-b] [1,4] oxazino [2,3,4- hi] indole-9-carboxylate; benzyl 5-methyl-1,2,7,8,10,11-hexahydro-9H-azepino [4,5-b] [1,4] oxazino [2,3,4- hi] indole-9-carboxylate; benzyl 6-fluoro-1,2,7,8,10,11-hexahydro-9H-azepino [4,5-b] [1,4] oxazino [2,3,4- hi] indole-9-carboxylate; benzyl 6-chloro-1,2,7,8,10,11-hexahydro-9H-azepino [4,5-b] [1,4] oxazino [2,3,4- hi] indole-9-carboxylate; benzyl 6-methyl-1,2,6b, 7,8,10,11, 11 a-octahydro-9H-azepino [4,5- b] [1,4] oxazino [2,3,4-hi] indole-9-carboxylate; benzyl 6- (trifluoromethyl)-1, 2,7,8,10,11-hexahydro-9H-azepino [4,5- b] [1,4] oxazino [2,3,4-hi] indole-9-carboxylate; benzyl 7,8,10,11-hexahydro-9H-azepino [4,5- b] [1,4] oxazino [2,3,4-hi] indole-9-carboxylatebenzyl;

benzyl 5-chloro-6-fluoro-1,2,7,8,10,11-hexahydro-9H-azepino [4,5- b] [1,4] oxazino [2,3,4-hi] indole-9-carboxylate; benzyl 5-fluoro-6-chloro-1,2,7,8,10,11-hexahydro-9H-azepino [4,5- b] [1,4] oxazino [2,3,4-hi] indole-9-carboxylate; benzyl 7,8,10,11-hexahydro-9H-azepino [4,5- b] [1,4] oxazino [2,3,4-hi] indole-9-carboxylate; benzyl 7,8,10,11-hexahydro-9H-azepino [4,5- b] [1,4] oxazino [2,3,4-hi] indole-9-carboxylate; 7-benzoyl 4,5,8,9,10,11-hexahydro-7H-azepino [4,5-b] pyrrolo [3,2,1-hi] indole; 7-benzoyl [4,5-b] pyrrolo [3,2,1- hi] indole; 7-benzoyl 2-methoxy-4,5,8,9,10,11-hexahydro-7H-azepino [4,5-b] pyrrolo [3,2,1- hi] indole; benzyl-5-methyl-4,5,8,9,10,11-hexahydro-7H-azepino [4,5-b] pyrrolo [3,2,1-hi]-7- carboxylate; 8,9,10,11-hexahydro-7H-azepino [4,5-b] pyrrolo [3,2,1- hi] indole-7-carboxylate; benzyl-2,3,4,5,8b, 12a-decahydro-lH-azepino [4', 5' : 4,5] pyrrolo [3,2,1- jk] carbazole-7-carboxylate; benzyl-1-chloro-2-fluoro-4,5,8,9,10,11-hexahydro-7H-azepino [4,5- b] pyrrolo [3,2,1-hi] indole-7-carboxylate; benzyl-2-chloro-4,5,8,9,10,11-hexahydro-7H-azepino [4,5-b] pyrrolo [3,2,1- hi] indole-7-carboxylate; benzyl-1-chloro-4,5,8,9,10,11-hexahydro-7H-azepino [4,5-b] pyrrolo [3,2,1- hi] indole-7-carboxylate; 10-benzoyl-5,6,9,10,11,12-hexahydro-4H, 8H-azepino [4', 5' : 4,5] pyrrolo [3,2,1- ij] quinolin-4- one; 10-benzoyl-2-fluoro-5,6,9,10,11,12-hexahydro-4H, 8H-azepino [4', 5' : 4,5] pyrrolo- [3,2,1-ij] quinolin-4-one; 10-benzoyl-2-chloro-5,6,9,10,11,12-hexahydro-4H, 8H-azepino [4', 5' : 4,5] pyrrolo-

[3,2,1-ij] quinolin-4-one; 10-benzoyl-6-methyl-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo- [3,2,1-ij] quinolin-4-one; 8H- azepino [4', 5' : 4,5]-pyrrolo [3,2,1-ij] quinolin-4-one; 10-benzoyl-2,3-dichloro-6-methyl-5,6,9,10,11,12-hexahydro-4H , 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-4-one; 8H-azepino [4', 5' : 4,5] pyrrolo- [3,2,1-ij] quinolin-4-one; 10-benzoyl-6- (trifluoromethyl)-5,6,9,10,11,12-hexahydro-4H, 8H- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-4-one; 10-benzoyl-5,6,8,9,10,11,12,12a-octahydro-4H, 7aH- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinolin-4-ol; and 10-benzoyl-4-methoxy-5,6,8,9,10,11,12,12a-octahydro-4H, 7aH- azepino [4', 5' : 4,5] pyrrolo [3,2,1-ij] quinoline.

All cited publications, patents, and patent documents are incorporated by reference herein, as though individually incorporated by reference. The invention has been described with reference to various specific and preferred embodiments and techniques. However, it should be understood that many variations and modifications may be made while remaining within the spirit and scope of the invention.