xii E

FUNGICIDAL OXIME CARBAMATES CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of my copending application, U.S. Serial No. 07/398,266, filed August 24, 1989 which in turn is a continuation-in-part of my application U.S. Serial No. 07/342,876, filed April 25, 1989.

BACKGROUND OF THE INVENTION Bellina U.S. 3,819,700 claims compounds of Formula i as fungicides for crop protection.

O

CH ₃ CQ)nS H

Hubele CH 66-16,259 claims compounds of Formula ii as fungicides for crop protection.

ii

Compounds of Formula iii are disclosed in the patent literature as antidotes for herbicides in U.S. 4,416,686, U.S. 4,426,221, U.S. 4,453,969, U.S. 4,453,974, and U.S. 4,475,945.

X = halogen

ill

Compounds of formula iv are disclosed in EP 293 667 A as fungicides for crop protection.

iv

Compounds of formula v are disclosed in U.S. 3,954,992 as fungicides for crop protection.

O

M3NH— LI

_/ =NOR NC

SUMMARY OF THE INVENTION A method of controlling plant disease, especially fungus , comprising the application of an effective amount of a compound of Formula I to the locus to be protected.

wherein:

A is C(-0)R, C(-0)OR ^: , C(=0)SR ¹ , P(-0)QR ² Q ¹ R ³ ; C(=0)NHR, S0 ₂ R ⁵ , S0 ₂ NR ⁶ R ⁷ ; Q and Q ¹ are independently oxygen, NR ⁸ or a direct bond; X is Cl or Br; provided that when X is Br, A is

C(-0)R; G is C(-L)R ⁹ , C(=L)NR ¹⁰ R ¹¹ , C(«0)OR ¹² , CN, SO ₂ NR ¹⁰ R ^1:L . or SO _m R ¹³ ;

L is 0 or S; m is 0, 1 or 2;

R is C-^-C^ alkyl, C ₂ -C ₂ o alkenyl, C ₂ -C ₂₀ alkynyl; C^-C _β alkyl, C ₂ -Cg alkenyl, C ₂ -C ₈ alkynyl, or C3-C7 cycloalkyl, each optionally substituted with halogen, Cι-C ₆ alkoxy, C ₂ -Cg alkoxyalkyl, C-^-Cg alkylthio, C3~Cg cycloalkyl, CN, or with a phenyl group substituted with 0-3 halogen and 0-2 groups selected from CH ₃ , CF3, CH3O, CN, CH3S, methylsulfonyl, dimethylamino, amino, phenyl or phenoxy, provided that when A is C(»0)NHR, R is not C ₂ alkenyl or C ₂ alkynyl; R is a phenyl ring or a C ₁₀ -C ₁₄ fused carbocyclic aromatic ring systems, wherein said rings are substituted with 0-4 halogen, 0-1 groups selected from -CH ₂ (CH ) _p CH -, -0(CH ₂ ) _p CH ₂ -, -S(CH ₂ ) _p CH ₂ -, -0(CH ₂ ) _p O, -0(CH ₂ ) _p S-, -R ⁴ N(CH ₂ ) _p CH ₂ -, -0(CH ₂ ) _p NR ⁴ -, and 0-2 groups selected from NH(C=0)OR ¹⁶ ,

SCN, C-^-C, _} alkyl, C ₁ -C ₄ haloalkyl, C ₂ -C ₄ alkoxyalkyl, C ₂ -C ₄ alkenyl, C ₂ -C ₄ haloalkenyl, C ₂ -C ₄ alkynyl, C ₃ -Cg cycloalkoxy, C ₃ -Cg cycloalkyl, N0 ₂ , ■ C(-0)R ¹⁴ , CN, OR ¹⁴ , C(«0)OR ¹⁴ , C(=0)NR ¹⁴ R ¹⁵ ,

NR ¹ R ¹⁵ , SR ¹⁴ , SOR ¹⁴ , S0 ₂ F, S0 ₂ C1 or S0 ₂ NR ¹⁴ R ¹⁵ , 2-, 3-, or 4-pyridyl, or phenyl substituted with 0-3 halogen and 0-2 groups selected from CH ₃ , CF3, CH3O, CN, CH ₃ S, methylsulfonyl, dimethylamino or amino;

R can additionally be a heterocyclic ring system of 3-8 atoms, ring-carbon-linked to the carbonyl group when A is C(=0)R or to the N when A is C(=0)NHR, containing 1 or 2 nitrogen atoms, or 1 nitrogen atom and 1 oxygen atom, or 1 nitrogen atom and 1 sulfur atom; or one or, if the ring size is greater

than 3, 2 oxygen atoms, provided that the oxygen atoms are not bonded to each other; or 1 or 2 sulfur atoms;

R can additionally be a heteroaromatic or fused heteroaromatic ring system, ring-carbon- linked to the carbonyl group when A is C(=0)R or to the N when A is C(»0)NHR, containing 5-10 atoms, wherein the heteroatoms comprise 1-3 nitrogen atoms, or 1-2 nitrogen atoms and one oxygen or sulfur atom, or 1-2 oxygen or sulfur atoms, these rings being substituted with 0-1 (-CH ₂ (CH ₂ ) _p CH ₂ -) or with 0-2 groups selected from CH ₃ , OCH ₃ , OCF ₃ , OCH ₂ CF ₃ , F, Cl, Br, OCH ₂ CH ₃ , N0 ₂ , C(-0)CH ₃ , N(CH ₃ ) ₂ , C0 ₂ CH ₃ , CON(CH ₃ ) ₂ , S0 ₂ N(CH ₃ ) ₂ , SCH ₃ , CN or CF ₃ ; R-l- is C^-C _{2 Q} alkyl, C ₃ -C _2Q alkenyl, C ₃ -C _2Q alkynyl; or C ₁ -C ₈ alkyl, C ₃ -C ₈ alkenyl or

C ₃ -C ₈ alkynyl, each optionally substituted with halogen, C^-Cg alkoxy, C ₂ -Cg alkoxyalkyl, C _j -Cg alkylthio, C ₃ -Cg cycloalkyl, CN or with a phenyl group substituted with 0-3 halogen and 0-2 groups selected from CH ₃ , CF ₃ , CH ₃ 0, CN, CH ₃ S, methylsulfonyl, dimethylamino, amino, phenyl or phenoxy; provided that, if R ¹ is alkenyl or alkynyl, the unsaturated carbons are not

bonded directly to the oxygen atom of i nC?-0; R ² and R ³ are independently selected from C ₁ -C ₄ alkyl, C^-C ₄ haloalkyl, benzyl or phenyl; alkyl; l substituted with 0-3 halogen, or is a phenyl group substituted with 0-3

halogen and 0-2 groups selected from CH ₃ ,

CF ₃ , CH3O, CN, CH ₃ S, methylsulfonyl, dimethylamino, amino, nitro, phenyl or phenoxy; R ⁶ is H, C ₁ -C ₄ alkyl substituted with 0-3 halogen, or R6 is a phenyl group substituted with 0-3 halogen and 0-2 groups selected from CH ₃ , CF ₃ , CH3O, CN, CH3S, methylsulfonyl, dimethylamino, amino, phenyl or phenoxy; R ⁷ is H or C ₁ -C ₄ alkyl substituted with 0-3 halogen, or R ⁶ and R ⁷ taken together with the nitrogen atom to which they are attached can be piperidine, pyrrolidine or morpholine, each substituted with 0-2 methyl groups; R ⁸ is H or C ₁ -C ₄ alkyl; R ⁹ is C^-C _β alkyl substituted with 0-3 halogen, or R ⁹ is phenyl substituted with 0-2 halogen, CH ₃ , CF ₃ , CH3O or CN; R ¹⁰ and R ¹¹ are independently H, C ₁ -C alkyl, ^c l~ ^c 4 haloalkyl, C ₂ -C ₄ alkoxyalkyl, or benzyl or phenyl, said benzyl or phenyl rings being substituted with 0-2 halogen,

CH ₃ , CF ₃ , CH3O or CN; or R ¹⁰ and R ¹¹ , taken together with the nitrogen atom to which they are attached, can be azetidine, piperidine, homopiperidine, pyrrolidine, or morpholine, each substituted with 0-2 methyl groups; R ¹² is C _j _-C ₁₂ alkyl or haloalkyl, or benzyl substituted with 0-2 halogen, CH ₃ , CF ₃ , CH3O or CN;

R ¹³ _; is C ₁ -C alkyl, haloalkyl or C ₂ -C ₄ alkoxyalkyl, C ₃ -C ₄ alkenyl, haloalkenyl.

alkynyl or haloalkynyl, or benzyl or phenyl, said benzyl or phenyl rings being substituted with 0-2 halogen, CH ₃ , CF ₃ , CH ₃ 0 or CN; R ¹⁴ is H, C ₁ -C ₄ alkyl, C -C ₄ haloalkyl, or

C ₂ -C ₄ alkoxyalkyl; C ₃ -C ₄ alkenyl, haloalkenyl, alkynyl or haloalkynyl; or benzyl or phenyl, said benzyl or phenyl rings being substituted with 0-2 halogen,

CH ₃ , CF ₃ , CH ₃ 0, CH ₃ S or CN; R ¹⁵ is H or C ₁ -C ₄ alkyl;

R ¹⁶ is C^-C alkyl, C ₃ -C ₄ alkenyl, or benzyl substituted with 0-2 halogen, methyl, trifluoromethyl, nitro or methoxy; and p is 1 or 2.

Also contemplated are compounds of Formula I,

wherein A is C(»0)R, C(=0)OR ¹ , C^OJSR ¹ , P(»0)QR ² Q ¹ R ³ ;

C(-0)NHR, S0 ₂ R ⁵ , S0 ₂ NR ⁶ R ⁷ ; Q and Q ¹ are independently oxygen, NR ⁸ or a direct bond; X is Cl or Br; provided that when X is Br, A is C(-0)R;

G is C(-L)R ⁹ , C(-L)NR ¹⁰ R ^1:L , C(-0)OR ¹² , CN,

SO ₂ NR ¹⁰ R ^ι:L , or SO _m R ¹³ ; L is O or S; m is 0, 1 or 2; R is C ₁ -C ₀ alkyl, C ₂ -C ₂₀ alkenyl, C ₂ -C ₂₀ alkynyl; ^^3 alkyl, C -C ₈ alkenyl, C ₂ -C ₈ alkynyl, or C ₃ -C ₇ cycloalkyl, each

optionally substituted with halogen, C _j -Cg alkoxy, C ₂ -Cg alkoxyalkyl, C-^-Cg alkylthio, ^c 3~ ^c 6 cycloalkyl, CN, or with a phenyl group substituted with 0-3 halogen and 0-2 groups selected from CH ₃ , CF ₃ , CH3O, CN, CH ₃ S, methylsulfonyl, dimethylamino, amino, phenyl or phenoxy, provided that when A is C(»0)NHR, R is not C ₂ alkenyl or C ₂ alkynyl;

R is a phenyl ring or a fused carbocyclic aromatic ring systems, wherein said rings are substituted with 0-4 halogen, and 0-1 groups selected from -CH ₂ (CH ₂ ) _p CH ₂ -, -0(CH ₂ ) _p CH ₂ -, -S(CH ₂ ) _p CH ₂ -, -0(CH ₂ ) _p O,

-0(CH ₂ ) _p S-, -R ⁴ N(CH ₂ ) _p CH ₂ -, -0(CH ₂ ) _p NR ⁴ -, and 0-2 groups selected from NH(C»0)OR ¹⁶ , SCN, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₂ -C ₄ alkoxyalkyl, C ₂ -C ₄ alkenyl, C ₂ -C ₄ haloalkenyl, C ₂ -C ₄ alkynyl, C ₃ -Cg cycloalkoxy, C ₃ -Cg cycloalkyl, N0 ₂ , C(-0)R ¹⁴ , CN, OR ¹⁴ , C(-0)OR ¹⁴ , C(«0)NR ¹⁴ R ¹⁵ , NR ¹ R ¹⁵ , SR ¹⁴ , SOR ¹⁴ , S0 ₂ F, S0 ₂ C1 or S0 ₂ NR ¹ R ¹⁵ , 2-, 3-, or 4-pyridyl, or phenyl substituted with 0-3 halogen and 0-2 groups selected from CH3, CF ₃ , CH ₃ 0, CN, CH3S, methylsulfonyl, dimethylamino or amino; R can additionally be a heterocyclic ring system of 3-8 atoms, ring-carbon-linked to the carbonyl group when A is C(«0)R or to the N when A is C(-0)NHR, containing 1 or 2 nitrogen atoms, or 1 nitrogen atom and 1 oxygen atom, or 1 nitrogen atom and 1 sulfur atom; or one or, if the ring size is greater than 3, 2 oxygen atoms, provided that the oxygen atoms are not bonded to each other; or 1 or 2 sulfur atoms;

R can additionally be a heteroaromatic or fused heteroaromatic ring system, ring-carbon- linked to the carbonyl group when A is

C(-O)R or to the N when A is C(«0)NHR, containing 5-10 atoms, wherein the heteroatoms comprise 1-3 nitrogen atoms, or 1-2 nitrogen atoms and one oxygen or sulfur atom, or 1-2 oxygen or sulfur atoms, these rings being substituted with 0-1 (-CH ₂ (CH ₂ ) _p CH ₂ -) or with 0-2 groups selected from CH ₃ , OCH ₃ , OCF3, OCH ₂ CF ₃ , F, Cl, Br, OCH ₂ CH ₃ , N0 ₂ , C(»0)CH ₃ , N(CH ₃ ) ₂ , C0 ₂ CH ₃ , CON(CH ₃ ) ₂ , S0 ₂ N(CH ₃ ) ₂ , SCH3, CN or CF ₃ ;

R ¹ is CJL-C ₂ O alkyl, C ₃ -C ₂₀ alkenyl, C ₃ -C ₂₀ alkynyl; or CJ-CJJ alkyl, C3-C3 alkenyl or C ₃ -C ₈ alkynyl, each optionally substituted with halogen, C^Cg alkoxy, C ₂ -C ₆ alkoxyalkyl, C^Cg alkylthio, C ₃ -Cg cycloalkyl, CN or with a phenyl group substituted with 0-3 halogen and 0-2 groups selected from CH ₃ , CF ₃ , CH ₃ 0, CN, CH ₃ S, methylsulfonyl, dimethylamino, amino, phenyl or phenoxy; provided that, if R ¹ is alkenyl or alkynyl, the unsaturated carbons are not

bonded directly to the oxygen atom of C-O; R ² and R ³ are independently selected from C^-C alkyl, C^-C ₄ haloalkyl, benzyl or phenyl;

R ⁴ is H or C ₁ -C ₄ alkyl; R ⁵ is C!-C ₄ alkyl substituted with 0-3 halogen, or R ⁵ is a phenyl group substituted with 0-3 halogen and 0-2 groups selected from CH ₃ , CF ₃ , CH3O, CN, CH ₃ S, methylsulfonyl, dimethylamino, amino, nitro, phenyl or phenoxy;

R ⁶ Ls H, C -C ₄ alkyl substituted with 0-3 halogen, or R6 is a phenyl group substituted with 0-3 halogen and 0-2 groups selected from CH ₃ , CF ₃ , CH ₃ 0, CN, CH ₃ S, methylsulfonyl, dimethylamino, amino, phenyl or phenoxy; R ⁷ is H or C ₁ -C ₄ alkyl substituted with 0-3 halogen, or R^ and R ⁷ taken together with the nitrogen atom to which they are attached can be piperidine, pyrrolidine or morpholine, each substituted with 0-2 methyl groups; R ⁸ is H or C^-C^ alkyl;

R ⁹ is C^- _Q alkyl substituted with 0-3 halogen, or R ⁹ is phenyl substituted with 0-2 halogen, CH ₃ , CF ₃ , CH ₃ 0 or CN; R ¹⁰ and R ¹¹ are independently H, CJL-C ₄ alkyl, ^c l~ ^c 4 haloalkyl, C ₂ -C ₄ alkoxyalkyl, or benzyl or phenyl, said benzyl or phenyl rings being substituted with 0-2 halogen, CH ₃ , CF ₃ , CH ₃ 0 or CN; or R ¹⁰ and R ¹¹ , taken together with the nitrogen atom to which they are attached, can be azetidine, piperidine, homopippridine, pyrrolidine, or morpholine, each substituted with 0-2 methyl groups; R ¹² is alkyl or haloalkyl, or benzyl substituted with 0-2 halogen, CH ₃ , CF ₃ , CH ₃ 0 or CN; R ¹³ is Cι~C ₄ alkyl, haloalkyl or C ₂ -C ₄ alkoxyalkyl, C ₃ -C ₄ alkenyl, haloalkenyl, alkynyl or haloalkynyl, or benzyl or phenyl, said benzyl or phenyl rings being substituted with 0-2 halogen, CH ₃ , CF ₃ , CH ₃ 0 or CN;

R ¹⁴ is H, C _j -C ₄ alkyl, C ₁ -C ₄ haloalkyl, or C ₂ -C ₄ alkoxyalkyl; C ₃ -C ₄ alkenyl, haloalkenyl, alkynyl or haloalkynyl; or benzyl or phenyl, said benzyl or phenyl rings being substituted with 0-2 halogen, CH ₃ , CF ₃ , CH ₃ 0, CH ₃ S or CN; R ¹⁵ is H or C^^ alkyl; R ¹⁶ is C-^-C alkyl, C ₃ -C ₄ alkenyl, or benzyl substituted with 0-2 halogen, methyl, trifluoromethyl, nitro or methoxy; and p is 1 or 2; provided that 1. when A is C(»0)SR ¹ or C(-0)OR ¹ , then G is not C(-L)NR ¹⁰ R ^ι:L or C(-0)OR ¹² ; and 2. when A is C(-0)NHR, and G is C(-L)NR ¹⁰ R ^1:L or C(»0)OR ¹² , then R is not unsubstituted phenyl or C _j -^ alkyl.

1. Preferred for ease of synthesis and/or fungicidal activity are compounds of Formula I wherein:

A is C(-0)R, C(-0)OR ¹ ,C(-0)NHR, or P(-0)QR ² Q ¹ R ³ ;

G is C(-O)NR ¹⁰ R ^1:L or C(-0)OR ¹² .

2. More preferred for ease of synthesis and/or fungicidal activity are compounds of Formula I wherein:

A is C(-0)R, or C(-0)NHR;

G is C(-O)NR ¹⁰ R ^1;L or C(=0)OR ¹² ;

X is Cl.

3. Even more preferred for ease of synthesis and/or fungicidal activity are compounds of Formula I wherein:

A is C(»0)R, or C(=0)NHR; G is C(=O)NR ¹⁰ R ^ι:L or C(=0)OR ¹² ; R is C _j -C ₂ alkyl substituted with a phenyl group, said phenyl group being substituted with 0-3 halogen and 0-2 groups selected from CH ₃ , CF ₃ , CH3O, CN, CH3S, methylsulfonyl, dimethylamino, amino, phenyl or phenoxy; or

R is a phenyl or naphthyl ring, substituted with 0-3 halogen and 0-2 groups selected from CH ₃ , CF ₃ , CH ₃ 0, CN, CH ₃ S, methylsulfonyl, dimethylamino, amino, phenyl or phenoxy;

R ¹⁰ and R ¹¹ are independently H, C ₁ -C ₄ alkyl, haloalkyl or benzyl substituted with 0-2 halogen, CH ₃ , CF ₃ , CH3O or CN; or R ¹⁰ and R ¹¹ , taken together with the nitrogen atom to which they are attached, can be piperidine, pyrrolidine or morpholine, each substituted with 0-2 methyl groups; and X is Cl.

4. Particularly preferred for ease of synthesis and/or fungicidal activity are compounds of Preferred 3 wherein: A is C(-0)R; G is C(-O)NR ¹⁰ R ¹¹ ; R is C _j -C ₂ alkyl substituted with a phenyl group, said phenyl group being substituted with 0-3 halogen and 0-2 groups selected from CH ₃ , CF ₃ , CH3O, CN, CH ₃ S, methylsulfonyl, dimethylamino, amino, phenyl or phenoxy; or

R is a substituted phenyl or naphthyl ring, wherein the substituent is selected from: 0-3 halogen and 0-2 CH ₃ , CF ₃ , CH ₃ 0, CN,

CH ₃ S, methylsulfonyl, dimethylamino, amino, phenyl or phenoxy; and X is Cl.

Also particularly preferred for ease of synthesis and/or fungicidal activity are compounds of Preferred 3, wherein: A is C(«0)NHR; G is C(-O)NR ¹⁰ R ¹¹ ; R is C ₁ -C ₂ alkyl substituted with a phenyl group, said phenyl group being substituted with 0-3 halogen and 0-2 groups selected from CH ₃ , CF ₃ , CH ₃ 0, CN, CH ₃ S, methylsulfonyl, dimethylamino, amino, phenyl or phenoxy; or

R is a substituted phenyl or naphthyl ring, wherein the substituent is selected from: 0-3 halogen and 0-2 CH ₃ , CF ₃ , CH ₃ 0, CN, CH ₃ S, methylsulfonyl, dimethylamino, amino, phenyl or phenoxy; and

X is Cl.

Specifically preferred are the following compounds: N-[[2-naphthylcarbonyl]oxy]-2-(dimethylamino)-

2-oxoethanimidoyl chloride; N-[[[(3,5-dichlorophenyl)amino]carbonyl]oxy]-2-

(dimethylamino)-2-oxoethanimidoyl chloride; N-[[[(2,6-dichlorophenyl)amino]carbonyl]oxy]-2- (dimethylamino)-2-oxoethanimidoyl chloride;

N-[[[[3,5-Bis(trifluoromethyl)phenyl]amino]- carbonyl]oxy]2-(dimethylamino)-2-oxo- ethanimidoyl chloride;

12784

14

N-[ [ [3,4-(dichloroρhenyl)amino]carbonyl]oxy]- 2-(dimethylamino)-2-oxoethanimidoyl chloride; N-[ [ [3,4-(dichloroρhenyl)amino]carbonyl]oxy]-2- oxo-2-piperidino ethanimidoyl chloride; N-[[[(3 ,5-dichlorophenyl)amino]carbonyl]oxy]- α-oxo-1-piperidineethanimidoyl chloride; N-[ [bis(2,2,2-trichloroethσxy)phosphinyl]oxy]- 2-(dimethylamino)-2-oxoethanimidoyl chloride;

N-[[[[(2-chlorophenyl)methyl]amino]carbonyl]- oxy]-2-(diethylamino)-2-oxoethanimidoyl chloride; N-[[([1,l-biphenyl]-4-yl)carbonyl]oxy]-2- (dimethylamino)-2-oxoethanimidoyl chloride;

N-[[[(3,5-difluorophenyl)amino]carbonyl]- - oxy]-α-oxo-l-piperidineethanimidoyl chloride;

N-[[(2-naphthalenyl)carbonyl]oxy]-α-oxo-1- piperidineethanimidoyl chloride; 2-(dimethylamino)-2-oxo-N-[[[(2,4,5-trichloro- phenyl)amino]carbonyl]oxy]ethanimidoyl chloride; 2-(dimethylamino)-2-oxo-N-[(1-oxooctadecyl)oxy] ethanimidoyl chloride; and 2-(dimethylamino)-2-oxo-N-[[(phenylmethoxy)- carbonyl]oxy]ethanimidoyl chloride.

Also preferred as intermediates useful in preparing the above compounds are: N-[(chlorocarbonyl)oxy]-2-dimethylamino-2-oxo- ethaneimidoyl chloride; and N-[(chlorocarbonyl)oxy]-α-oxo-l-piρeridine- ethanimidoyl chloride.

Also contemplated are agriculturally suitable compositions of the above-described compounds, comprising a fungicidally active amount of said compound and at least one of the following: surfactant, solid diluent or liquid diluent.

DETAILED DESCRIPTION OF THE INVENTION Synthesis

The compounds of Formula I can be prepared from compounds of Formula III and an appropriate electrophilic reagent of Formula II in an inert solvent with or without a base used either as a catalyst or acid scavenger. Suitable solvents include polar aprotic solvents such as acetonitrile, dimethylformamide, or dimethylsulfoxide; ethers such as tetrahydrofuran, dimethoxyethane, or diethyl ether; ketones such as acetone or 2-butanone; hydrocarbons such as toluene or benzene; or halocarbons such as dichloromethane or chloroform. Appropriate bases include alkali metal alkoxides such as sodium methoxide or potassium iai±-butoxide, inorganic bases such as sodium hydride or potassium carbonate, or tertiary amines such as triethylamine, pyridine, l,8-diazabicyclo[5.4.0] undec-7-ene (DBU) , or triethylenediamine (DABCO) . The reaction temperature can vary between 0°C and 150° for periods of 1 to 72 hours depending on the choice of base, solvent, temperature, and substrates.

Compounds of Formulas Ia-f can be prepared from combining an appropriate electrophilic reagent of

Formula Ila-f with an oxime of Formula III by several processes which are summarized in the following equations.

G-ONOH + OCNR _. G-C»N-0-C(«0)NHR i ^{■ G} i- HI Ha. Ia

HI + Clξ-OOR ¹ * G ^G -"C?-N-0-C(-0)OR ¹

Hϋ l

HI + C1C(0-)SR ^{1 G} G--?C«N-0-C(-0)SR

Hz IS.

HI + C1(0«)CR G-C»N-0-C(»0)R

X

HI + C10 ₂ SR ⁵ G-C»N-0-S0 ₂ R ^!

X

US Is

HI + C1P(-0)QR ² Q ¹ R ³ H£ If.

A novel method of preparation of compounds of Formula Ia-c comprises sequential preparation of the

novel chloroformate g. by reaction of compounds of Formula III with phosgene in the presence of organic bases such as N,N-diethylaniline and pyridine, followed by the appropriate RNH ₂ , R^OH or R-^SH compound in the presence of a suitable acid scavenger such as N,N-diethylaniline, pyridine or triethylamine,

G- 1C--NOH ^• > G-C •NOC(-0)Cl -^ G-C-NOC-W-Z-A ¹ 1

Λ Base X RNH ₂

R ¹ OH or R^-SH

Base

III la

I W-Z-A ¹ = C(»0)NHR

C(-0)OR ¹ Cζ-OJSR ¹

Compounds of Formula Id can be prepared from compounds of Formula III and a carboxylic acid Ilg in the presence of a coupling auxiliary reagent such as, but not limited to, N,N-dicyclohexyl carbodiimide (DCC) or 2,2'-dipyridyldisulfide (DPDS) .

DCC or DPDS

G-C-NOH + HOC(»0)R ^ G-C«NOC(=0)R X X

Alternatively, the hydroximoyl chlorides or bromides of Formulas Ia. b. d. e. f can be prepared from the corresponding aldoximes of Formula IV with

halogens (see H. Metzger, Herstellung von Oximen, Houben-Weyl, Methoden der orαanische Chemie. E. Miller, Editor, Vol. 10(4), 4th ed. , p. 98, Thieme, Stiittgart, 1968), N-chlorosuccinimide (see K. C. Liu, B. R. Shelton, and R. K. Howe, J. Orσ. Chem.. 1980, jL5.,3916), or N-bromosuccinimide (see C. Grundmann and R. Richter, J. Orσ. Chem., 1968, 32,476).

X=C1. Br

IV I

Hydroximoyl chlorides of Formula lb and id. can be prepared by the reaction of nitro compounds of Formula Ih with two equivalents of an organic base such as triethylamine and two equivalents of a chloroforraate of Formula lib or an acid chloride of Formula lid (see T. Shinizer, Y. Hayashi, H. Shibafuchi, and K. Teramura, Bull. Chem. Soc. ilaEan. 1986, 5 , 2827).

2 eq. Base

GCH ₂ N0 ₂ + 2 C1C(=0)0R G-C=N-0-C(=0)OR ->

2 eq. Base I + 2 C1C(»0)R . G-C«N-OC(-0)R

UΛ IΛ Cl

The thiocarboxamide and thioketone compounds of

Formula I can be prepared from the carboxamide or ketone compounds, respectively, of Formula I by methods described elsewhere (see S. Scheibye, E. S. Pedersen and S. O. Lawesson, Bull. Soc. Chim. Belσ.. 1978, SJ_, 229 and G. Lajore, F. Lepine, L.

Maziak and B. Belleau, Tet. Letters. 1983, 2A, 3815).

G-C-NO-A G-C-NO-A X

I, G - C(-O)NR ¹⁰ R ^i:L , I, G - C(-S)NR ¹⁰ R ^1:L , C(-0)R ⁹ C(-S)R ⁹

Compounds of Formula I can also be prepared by conversion of other compounds of Formula I by standard methods of organic reactions, recognizable by those skilled in the art, such as, but not limited to, reduction and oxidation.

The α-chloroaldoximes of Formula III can be prepared by treating amines of Formula V with sodium nitrite and hydrochloric acid (see G. S. Skinner, J. Am. Chem. Soc. 1924, ,731).

G-CH ₂ NH ₂ NaN0 ₂ G-C-NOH

*

H ₂ 0 HCI

III

The α-chloroaldoximes of Formula III can also be prepared from aldoximes of Formula VI by treatment with N-chlorosuccinimide (see K. E. Larsen and K. B. G. Torsell, Tetrahedron. 1984, 4JI, 2985) or t-butylhypochlorite (see C. J. Peake and J. H. Strickland, Svnth. Comm.. 1986, 16, 763).

Some α-haloaldoximes of Formula III may be prepared from amide oximes VII by treatment with sodium nitrite in hydrohalic acid solution (see M. Kocevar, S. Polanc, M. Sollner, M. Tisler and B. Vercek, Svnth. Comm.. 1988, IS., 1427).

HX G-C-NOH ^ G-C-NOH

NH ₂ NaN0 ₂ X

H III

The α-haloaldoximes of Formula III can be prepared from trihalomethyl compounds of Formula VIII by basic hydrolysis in the presence of hydroxylamine (see A. P. Kozikowski and M. Adamczyk, J. Orσ. Chem.. 1983, , 366).

G-CX ₃ NH ₂ OH G-C-NOH > ^x

NaOH

VH III

The α-haloaldoximes of Formula III can be prepared by the reaction of nitrile N-oxides of Formula IX with hydrohalic acids (see C. Grundmann, V. Mini, J. M. Dean, and H. -D. Frommeld, Justis iebjgs Ann. Cheπ , 1965, £12,191).

+ - G-C≡N-0 HX G-C-NOH

IΣ III

The nitrile N-oxides of Formula IX can be prepared by several methods well known in the chemical

art (for a summary of methods, see T. Shimizu, Y. fiayashi, and K. Taramura, Bull. Soc. Chem. Jpn.. 1984, 5_7,2531). The most familiar method involves treating an α-chloroaldoxime of Formula X with an inorganic base such as sodium hydroxide or sodium carbonate or an organic base such as triethylamine followed by trapping the nitrile N-oxide of Formula VII with a hydrohalic acid. A new α-haloaldoxime of Formula III is produced.

+ -

G-C-NOH G- i :ι_ -> C≡N-0 G-C-NOH

X

2 IS III

The carboxamide and carboxylic acid ester compounds of Formula III can be prepared by the procedures taught in the U.S. Patents 3,557,089, 3,557,190, and 3,560,555.

-O)NR ¹⁰ R ^1:L , C0 ₂ R ¹²

III

The thiocarboxamide compounds of Formula III can be prepared from the trihalothioacetamides of Formula XI which are obained from the haloimmonium chlorides of Formula XII. See W. Walter and K. -D. Bode, Anσew. Chem. Infcernat. Edit.. 1966, 5., 447 for a review of the syntheses of thiocarboxamides.

+

I II HI

X = halogen C = C(=S)NR ¹⁰ R ^{ι:L i} f*

The cyano compound of Formula III can be prepared by methods already reported (see

A. P. Kozikowski and M. Adamczyk, J. Org. Chem., 1983, 48, 366).

NC-C-NOH X

HI X - Cl

The ketone compounds of Formula III can be prepared from halomethyl ketones of Formula XIII by treatment with an alkyl nitrite and hydrochloric acid (see N. Levin and W. H. Hartung, Orq. Synthesis. 1944, 21, 25).

:CH ₂ X + alkyl ONO

XIII X - Cl III X - Cl

The ketone compounds of Formula III can also be prepared from halomethyl ketones of Formula XIII by treatment with dimethyl sulfide to afford compounds of Formula XIV. which are then treated with sodium nitrite and hydrochloric acid (see Y. Ofsuji, Y. Tsujii, A. Yoshida and E. Imoto, Bull Chem. Soc. Japan. 1971, 44, 223).

NaNO-

«CH ₂ X + (CH ₃ ) ₂ S R . ⁹ ?CCH ₂ ⁺ S(CH ₃ ) ₂ R ⁹ BC. >NOH

^

X" HCI X

XIII XIV HI X - Cl

The ketone compounds of Formula III can be prepared from β-ketosulfoxides of Formula XV by treatment with sodium nitrite in hydrohalic acid solution (see Y. Otsuji, Y. Tsujii, A. Yoshida and E. Imoto, Bull. Chem. Soc. Japan. 1971, !!/ 219).

HX

X2 HI

The ketone compounds of Formula III can also be prepared from compounds of Formula VI by treatment with chlorine gas (see G. Casnati and A. Ricca, Tet. Letters. 1967, 327 and Y. H. Chiang, J. Orα. Chem.. 1971, 23., 2146).

25

Cl-

G-C-NOH G-C-NOH > H

VI G-R ⁹ CO HI X

The thioalkyl and thioaryl compounds of Formula III can be prepared from dihaloformaldoxime VI (see D. Chiarino, M. Napoletano and A. Sala, Svnth. Comm.. 1988, 13., 1171 and D. M. Vyas, Y. Chiang and T. W. Doyle, Tet. Letters. 1984, 25, 487) by reaction with thiols and one equivalent of an organic base such as triethylamine (see M. H. Benn, Can. J. Chem.. 1964, 12., 2393).

R ¹³ SH

X-C-NOH -> G-C-NOH

Base

XVI X - Br,Cl HI G - R ¹³ S

The sulfoxide and sulfone compounds of Formula HI can be prepared from compounds of Formula III (G - R* S) by oxidation using one or two equivalents, respectively, of oxidants such as hydrogen peroxide or organic peracids, such as peracetic acid.

[ 0 ]

G- ^• ?C-NOH G-C-NO

^~ 7 1 H

II G- R ¹³ S HI G - R ¹³ SO, R ¹³ S0 ₂

The sulfone compounds of Formula III can also be prepared from compounds of Formula Ih (G - R ¹³ S0 ₂ ) according to methods already reported (see P. A. Wade and H. R. Hinney, J. Am. Chem. Soc.. 1979, Ml, 1319).

GCH ₂ N0 ₂ G-C-NOH

~> I X

Ji G - R ,1 ^J ~3 ³ S0 ₂ HI X - Br

Alternatively, the sulfonylcarbohydroximoyl chlorides of Formula III can be prepared from α-diazosulfones of Formula XVII and nitrosyl chloride (see J. C. Jagt, I. van Buuren, J. Strating and A. M. van Leusen, Synth. Commun.. 1974, 1,311).

NOX

XVII HI " G-R ₄ S0 ₂ X-Cl

Those skilled in the art will recognize compounds of Formula I are O-substituted oximes which can be of either the syn or anti form. The scope of the specification referring to compounds of Formula I includes both stereoisomeric oxime forms either as a specific steroisomer, a mixture of stereoisomers, or as any reciprocal mixture ratio of the two stereoisomeric forms.

The examples which follow are representative of the production of the novel oximes of Formula I.

EXAMP E 1 N-TΓ Ϊ2.6-(dichlorophenyl)aminolcarbonylloxyl- 2-(dimethylamino)-2-oxo-ethanimidovl chloride DBU (3 drops) is added to a solution of 2-chloro-2-hydroxyimino-N,N-dimethylacetamide (3.0g) and 2,6-dichlorophenyl isocyanate in lOOmL of THF at room temperature. After stirring the reaction overnight, the solvent is removed in vacuo leaving a white solid. The solid is triturated with chloroform and collected by vacuum filtration giving 4.Og (59%) of the title compound, m.p. = 182-185°C.

EXAMPLE 2

N-rπT3.5-bis(trifluoromethypphenvllamino)1- carbonvl1oxv1-2-fdimethvlaminon-2- oxoethanimidovl chloride DBU (3 drops) is added to a solution of

2-chloro-2-hydroxyimino-N,N-dimethylacetamide (3.Og) and 3,5-bis(trifluromethyDphenyl isocyanate (5.1g) in 100 mL of THF at room temperature. After stirring the reaction overnight, the solvent is removed in vacuo leaving a white solid. Trituration with carbon tetrachloride gives product as a white solid; yield 7.45g (92%), m. p. 184-187°C.

EXAMPLE 3 N-rrr3,5-(dichlorophenyl)amino1carbonyπoxv1-2- (dimethylamino)-.2-oxoethanimidovl chloride DBU (10 drops) is added to a solution of 2-chloro-2-hydroxyimino-N,N-dimethylacetamide (15.0g) and 3,5-dichloroρhenyl isocyanate (18.8g) in 200 ml of THF at room temperature. After stirring the reaction for two hours, the solvent is removed in vacuo. The solid is stirred overnight in 200 mL of ethyl acetate. The white solid is collected by vacuum filtration giving 29.4g (87%) of the title compound, m. p. - 180-182°C.

EXAMPLE 4 N-rrrrO-trifluoromethvl)phenvnaminolcarbonyl!oxv)1- 2- ( imethylamino)-2-oxoethanimidovl chloride DBU (3 drops) is added to a solution of

2-chloro-2-hydroxyimino-N,N-dimethylacetamide (3.0g) and 3-trifluoromethylphenyl isocyanate (3.7g) in 100 mL of THF at room temperature. After stirring the reaction for two hours, it is left undisturbed for two days. The solvent is removed in vacuo leaving an oil which slowly crystallized. After five hours, the solid is triturated with n-chlorobutane giving product as a white solid; yield 4.6g (69%), m. p. 128-132°C.

EXAMPLE 5

N-rrr3.4-(dichlorophenvl)aminolcarbonvlloxvl -?.- (dimethylamino)-2-oxoethanimidovl chloride DBU (3 drops) is added to a solution of 2-chloro-2-hydroxyimino-N,N-dimethylacetamide (3.Og) and 3,4-dichlorophenyl isocyanate (3.75g) in 100 mL of THF at room temperature. After stirring the reaction

overnight, the solvent is removed in vacuo. The solid is triturated with ethyl acetate giving product as a white solid; yield 2.4g (39%), m. p. - 144-146°C.

EXAMPLE 6 Ethvl-rrrr3.5-(dichlorophenvl)amino ^" lcarbonvl1oxv1- iminol-2-chloroacetate DBU (3 drops) is added to a solution of ethyl chlorooximinoacetate (3.0g) and 3,5-dichlorophenyl isocyanate (3.8g) in lOOmL of THF at room temperature. After stirring the reaction overnight, the solvent is removed in vacuo. The solid is triturated with n-chlorobutane giving product as a white solid; yield 5.45g (80%), m. p. - 152-154°C.

EXAMPLE 7 N-T3r5-fflichlQrQfrenspylQgy)1-2- (dimethylamino)-2-oxoethanimidovl chloride

A solution of 3,5-dichlorobenzoyl chloride (4.2g) in 20mL of THF is added to a solution of 2-chloro-2-hydroxyimino-N,N-dimethylacetamide (3.Og) in 80mL of THF at room temperature. Triethylamine (2.0g, 2.8mL) is added dropwise to the stirred solution maintaining the reaction temperature between 25-28°C with external cooling. Triethylamine hydro¬ chloride precipitates, and the reaction is further stirred three hours. The solid is removed by vacuum filtration, and the filtrate removed in vacuo leaving product as a white solid; yield 6.2g (95%), m. p. - 92-95°C.

EXAMPLE 8 N-rrr4.β-(dichloro-2-pvrimidinvl)amino1carbonvl ^' loxv1- 2-(dimethylamino)-2-oxoethanimidovl chloride DBU (3 drops) is added to a solution of 2-chloro-2-hydroxyimino-N,N-dimethylacetamide (3.0g) and 4,6-dichloro-2-pyrimidinyl isocyanate (3.8g) in lOOmL of THF at room temperature. After stirring the reaction overnight, the solvent is removed in vacuo. The pale green solid is triturated with warm n-chlorobutane and collected by vacuum filtration from the warm suspension giving product as a white solid; yield 4.7g (69%), m. p. = 167-169°C.

EXAMPLE 9 N-rrr3.5-(dichlorophenvl)amino1carbonvlloxvl- 2-amino-2-oxoethanimidovl chloride DBU (3 drops) is added to a mixture of 2-chloro-2-hydroxyimino-acetamide (2.45g) and

3,5- _^ dichlorophenyl is ^' ocyanate (3.8g) in lOOmL of THF at room temperature. After 40 minutes, a fine white precipitate develops. After stirring the reaction overnight, the precipitate is collected by vacuum filtration giving product as a white solid; yield 2.9g (47%), m. p. - 224-226°C (dec).

EXAMPLE 1Q N-rr4-(bromophenvl)sulfonyl1oxy1-2- (dimethylamino)-2-oxoethanimidovl chloride

DBtf (1.7mL) in lOmL of THF is added to a solution of 2-chloro-2-hydroxyimino-N,N-dimethyl- acetamide (1.5g) and 4-bromobenzenesulfonyl chloride (2.6 g) in 50mL of THF at room temperature. The amine salt precipitates, and the reaction is stirred an additional 24 hours. DBU (0.8mL) in lOmL of THF is

added, and the suspension is stirred another three hours. The precipitate is removed by vacuum filtration, and the filtrate reduced in vacuo leaving product as a white crystalline solid; yield 2.3g (63%), m. p. » 134-136°C.

EXAMPLE 11 2-(dimethylamino)-N-[bis(2,2,2-trichloroethoxy)- . phosphinyloxy]-2-σxoethanimidoyl chloride

₂

DBU (1.7mL) in 10 mL of THF is added to a solution of 2-chloro-l-hydroxyimino-N,N-dimethyl acetamide (1.5g) and bis(2,2,2-trichloroethyl) phosphorochloridate (3.8 g) at room temperature. The amine salt precipitates, and the reaction is stirred an additional 18 hours. The precipitate is removed by vacuum filtration. The filtrate is reduced in vacuo and the residue purified by flash chromatography on silica gel (1:2 hexane:ethyl acetate as eluant). The crude material is triturated in dichloromethane and hexane to give the product as a white solid; yield 850mg (17%), m. p. = 88-90°C.

32

EXAMPLE 12

N-[4-Phenylbenzoyloxy]-2-dimethylamino-

2-oxoethanimidoyl chloride

A solution of triethylamine (5.6 mL) in 80 mL of THF is added to a solution of 2-chloro-2-hydroximino- N,N-dimethyl-acetamide (6.0 g) and 4-biphenylcarboxyl- chloride (8.8 g) in 120 mL THF at room temperature. The amine salt precipitates, and the reaction mixture is stirred an additional 2 hours. The precipitate is removed by vacuum filtration, and the filtrate is reduced in vacuo leaving the crude reaction product as an off-white solid. The crude product is recrystallized from 1-chlorobutane to yield 5. 4 g (41%) off-white crystalline solid, m.p. - 126-128°C.

EXAMPLE 13

*= ^s °=γ -_.

Cl

N-[Ethoxycarbonyloxy]-2-phenylsulfonyl- ethanimidoyl chloride

A solution of triethylamine (5.6 mL) in 20 mL of THF is added dropwise to a solution of phenylsulfonylnitromethane (4.0 g) and ethyl chloroformate (3.9 mL) in 100 mL of THF at 0°C. A precipitate forms and the reaction mixture turns orange. The reaction mixture is stirred an additional 2 hours at room temperature. The precipitate is removed by vacuum filtration and the filtrate is reduced in vacuo leaving the crude reaction product as an orange semi-solid. Trituration in 1-chlorobutane and hexane provides the crude product as a dark amber solid; crude yield 5.0 g, 86% yield. A 2.5 g portion of the crude product was further purified by flash chromatography (2:1 hexane:ethyl acetate as eluant). The material is triturated in 1-chlorobutane and hexane to yield 1.0 g of white solid, m.p. 82-84°C.

EXAMPLE 14 Ethanimidoyl chloride, 2-(dimethylamino)- N-(2-naphthalenylcarbonyloxy)-2-oxo-

To a stirred solution of 2-chloro-2-hydroxy- imino-N,N-dimethylacetamide (10.52 g) in 150 mL of THF at 10°C is added 2-naphthoyl chloride (13.34 g) , follwed by triethylamine (9.76 mL) . After 3.5 hours, the mixture is filtered and the filtrate evaporated in vacuum to a white solid. The solid is dissolved in ethyl acetate and the solution washed with water, IN HCI, water, saturated sodium bicarbonate solution, and saturated brine, then dried (MgS0 ), filtered and evaporated in vacuum to a white solid residue. Recrystallization from 1-chlorobutane provided the title product as 14.43 g (68% of theoretical) of white solid, m.p. 141-143°C.

EXAMPLE 15

Ethanimidoyl bromide, 2-(dimethylamino)-N-

(2-naphthalenylcarbonyl-oxy)-2-oxo

A solution of 2-chloro-2-hydroxyimino-N,N- dimethylacetamide (1.42 g) in 50 mL of THF was cooled to -15°C, treated with N,N-diisopropyl-N-ethylamine (1.6 mL) , and filtered after 2 minutes (to remove solid) directly into a solution of 2-naphthoyl bromide in 75 mL of THF at -50°C. The mixture was stirred for 2 hours without cooling, then evaporated to an oily solid. Crystallization from 1-chlorobutane and filtration provided a solid and a filtrate. The filtrate was evaporated to a solid, and the solid recrystallized from hexane, providing the title product as a white solid, m.p. 128-130°C.

Mass spectral analysis showed m/e 349/351 (m + 1 for title product, with 1 Br) . Analysis Calculated for C ₁₅ H ₁₃ BrN ₂ θ3: C, 51.6; H, 3.8; N, 8.0%.

Analysis Found: C, 51.8; H, 4.0; N, 8.0%.

EXAMPLE 16 Ethanimidoyl chloride, N-(((l,l'-biphenyl))- 2-yl)carbonyloxy))-2-(dimethylamino)-2-oxo-

To a solution of 2-chloro-2-hydroxyimino-N,N- dimethylacetamide (2.60 g) in 50 mL of N,N-dimethylfσrmamide was added 2-biphenylcarboxylic acid (3.42 g), followed by N,N'-dicyclohexyl- carbodiimide (3.56 g) . The next day the mixture was filtered, the filtrate diluted with ice water, and the mixture extracted with ethyl acetate. The ethyl acetate solution was washed with water, IN HCI, water, saturated sodium bicarbonate solution, and saturated brine, dried (MgS0 ₄ ), filtered and the filtrate evaporated to a colorless oil. Chromatography of the oil on silica gel with 25% EtOAc in CHC1 ₃ provided a solid, on evaporation of eluent, which was recrystallized from hexane to give the title product, m.p. 68-72°C.

EXAMPLE 17 Ethanimidoyl chloride, N-(((butylthio)- carbonyloxy))-2-(dimethylamino)-2-oxo-

2-Chloro-2-hydroxyimino-N,N-dimethylacetamide (2.20 g) was dissolved in 100 mL THF. n-Butyl chlorothiolformate (2.23 g) was added to the solution at room temperature. The solution was cooled to 10°C,

then triethylamine was added to the solution. The reaction was allowed to warm to room temperature. After stirring the reaction overnight, it was vacuum filtered and the filtrate was evaporated to an oil. The oil was dissolved in ethyl acetate and washed with water, IN HCI, NaHC0 ₃ solution and brine. The ethyl acetate solution was dried over MgS0 ₄ , vacuum filtered an the filtrate was evaporated to a yellow oil. The title compound was isolated as a colorless oil (0.64 g, 19%) after chromatographing the yellow oil on silica gel with chloroform, then chloroform/ethyl acetate, 9/1.

EXAMPLE 18

Ethanimidoyl chloride, N-(((4-aminophenyl)- sulfonyloxy))-2-(dimethylamino)-2-oxo-

Into a stirred suspension of 7.77 g of ethanimidoyl chloride, 2-(dimethylamino)-N-(((4- nitrophenyl)sulfonyloxy))-2-oxo- in 39.5 mL of acetic acid and 7.9 mL of water was added, portionwise over a 30 minute period, 6.87 g of iron powder. The temperature was kept at 20-24°C by application of an ice bath as needed. Thirty minutes after completion of the iron addition, the mixture was filtered and the solid rinsed with acetic acid.

Extraction of the solid by N,N-dimethylformamide (DMF) followed by dilution of the DMF extract with ice water, provided a precipitate of the title product as 5.3 g (75% of theor.) of white solid, m.p. 148°C, dec. Recrystallization from methylene chloride/hexane provided the analytical sample, m.p. 153-154°C, dec. Analysis Calculated for C ₁₀ H ₁₂ ClN ₃ O S: C, 39.3, H, 4.0; N, 13.7%.

Analysis Found: C, 40.1; H, 4.2; N, 13.4%.

EXAMPLE 19 Ethanimidoyl chloride, 2-(dimethylamino)-2-oxo-

N-(((phenylmethoxy)carbonyloxy))

Benzyl chloroformate (2.16 mL) was added to a solution of 2-chloro-2-hydroxyimino-N,N-dimethyl- acetamide (2.28 g) in 100 mL of THF; after the solution was cooled to 10°C, triethylamine (2.11 mL) was added, and the mixture stirred overnight without cooling. The mixture was filtered, the filtrate evaporated to an oil, and the oil dissolved in ethyl acetate. The ethyl acetate solution was washed with water, IN HCI, water and saturated sodium bicarbonate solution, dired (MgS0 ₄ ), and evaporated to an oil, which solidified. The solid was recrystallized from 1-chlorobutane/hexane, providing the title compound as a white solid, m.p. 84-86°C.

EXAMPLE 20 Preparation of chloroformate of 2-chloro-2- hydroxyimino-N,N-dimethylacetamide

Into a stirred, N ₂ -blanketed suspension of 2-chloro-2-hydroxyimino-N,N-dimethylacetamide (15.06 g, 0.1 mole) in toluene (150 mL) at 20°C was run liquid phosgene (-15 mL, -0.22 mole). During a 10 minute period a solution of N,N-diethylaniline (17 mL, 0.11 mole) and pyridine (4 drops) in toluene (~10 mL) was added, with the temperature held to 20-24°C during the addition; the reaction was mildly exothermic during the addition and for a few minues thereafter. After 23 hours the solid (N,N-diethylaniline hydrochloride) was filtered off and the filtrate stripped (38°C bath) to an oil which is the product

38

chloroformate. It can be used directly, or further purified as indicated. The oil was dissolved in BuCl ("100 mL) , diluted to-t e cloud point with hexane, and restripped to an oil, which solidified to a light-orange solid under a nitrogen stream. The solid was dissolved in 100 mL of hot cyclohexane, and the supernatant decanted from a little insoluble oil; the oil was extracted with 25 mL of hot cyclohexane, and the combined, hot, turbid extracts treated with MgS0 ₄ (6 g) to soak up some of the oil present, and filtered.

The filtrate was stirred as it cooled until some grease, then some solid had formed, then filtered. The filtrate was stirred and cooled to 20°C, substantial white solid precipitating. After dilution with 20 mL of hexane, and cooling to 10°C the mixture was filtered, and the white solid product dried overnight in a nitrogen-swept vacuum oven (33°C).

Yield of white chloroformate: 11.4 g (54% of theor.); m.p. 68-70°C.

be prepared by similar methods include, but are not limited to those shown in the Table below:

R ¹⁰ R ^I:L N m.p. (°C) -

N

Et ₂ N (Bu,Me)N

EXAMPLE 21

Ethanimidoyl chloride, 2-(dimethylamino)-N- (((2,6-dimethylphenyl)aminocarbonyloxy))-2-oxo-

The chloroformate of 2-chloro-2-hydroxyimino-N,N- dimethylacetamide (2.08 g) was dissolved in 100 mL of THF. The solution was cooled to 0°C, then 2,6-dimethylaniline (1.2 mL) was added to the solution. Triethylamine (1.36 mL) was added to the solution with the temperature at 0°C. The reaction was allowed to warm to room temperature. After stirring the reaction for 2.5 hours, the reaction was vacuum filtered and the filtrate evaporated, leaving an orange oil. The oil was dissolved in ethyl acetate and washed with water, acid, NaHC0 ₃ and brine. The ethyl acetate solution was dried over MgS0 ₄ , vacuum filtered and the filtrate was evaporated to a white solid. The solid was recrystallized from butyl chloride/hexane and collected by vacuum filtration giving 1.27 g (44%) of the title compound, m.p. 160-164°C.

EXAMPLE 22 Preparation of ethanimidoyl chloride, N- (((3,5-dichlorophenyl)amino-carbonyloxy))-2- (dimethylamino)-2-thioxo

To a solution of 0.53 g ethanimidoyl chloride, N-(((3,5~dichlorophenyl)amino-carbonyloxy))-2-dimethyl- amino)-2-oxo dissolved in 50 mL of CH ₂ C1 ₂ was added 0.35 g of Lawessσn's reagent. The yellow solution was stirred for four days at room temperature. After concentration to one-half the original volume, the solution was flash chromatographed, eluting with 25% ethyl acetate/hexanes. The product had a Rf of 0.3 and 0.27 g (52%) of yellow solid were obtained; m.p. 156-157°C.

EXAMPLE 23 Preparation of 1-piρeridinethanimidoyl chloride, N-(((3,5-dichloroρhenyl)-amino-carbonyloxy))-α-oxo

To a solution containing 9.53 g of

1-piperidineethanimidoyl chloride, N-hydroxy-α-oxo-, and 9.40 g of 3,5-dichlorophenylisocyanate, dissolved in 300 mL THF, was added 3 drops of DBU. The solution was stirred at room temperature overnight. The solvent was removed in vacuo to yield a white solid. The material was recrystallized by dissolving in hot

acetone, cooling, and adding hexanes to produce 12.7 g (67%) of the title compound, following vacuum filtration, m.p. 185-186°C.

Preparation of 1-piperidineethanimidoyl chloride,

N-hydroxy-α-oxo-

A suspension of 47.6 g of piperidine, l-((2-(hydroxyimino)-l,3-dioxobutyl))- in a mixture of 100 mL H ₂ 0 and 100 mL acetic acid was heated to 45°C, then cooled to 30°C. Chlorine gas (11 mL) was condensed and added dropwise to the suspension over a 1 hour period, while maintaining the temperature less than 35°C. At the start of the chlorine addition, any remaining starting material dissolved. After half of the required amount of chlorine had been added, a white solid began to form. The mixture was stirred at room temperature for 15 minutes, following completion of the chlorine addition, then cooled to 2°C. Vacuum filtration and cold water wash yielded a white solid which was recrystallized from boiling CH ₂ C1 ₂ . Yield - 30.6 g (67%), m.p. 129-130°C.

EXAMPLE 24 Preparation of piperidine, l-((2-hydroxyimino)- 1,3-dioxobutyl))-

The above was prepared by dissolving 23.7 mL of piperidine in 100 mL H ₂ 0. After cooling to 3°C, diketene was added dropwise over 10 minutes, causing an exotherm to 32°C. The mixture was stirred while cooling to 5°C for 10 minutes. 16.6 g of sodium nitrite was added in three portions, keeping the temperature less than 10°C whereupon the mixture was stirred for 30 minutes. Under a nitrogen blanket, 21 mL of concentrated HCI was added portionwise over 10 minutes, keeping the temperature <35°C. After all of the acid had been added, the suspension was cooled to "2°C and stirred at that temperature for 45 minutes. Vacuum filtration, followed by a cold water wash yielded an off-white solid which was partially dried by filtration suction. The material was used without further characterization in the above step.

The following Table lists representative compounds of this invention, which can be prepared by one or more of the methods illustrated in the preceding Examples. The Table is not intended to be all-inclusive. The formula:

X ¹ -B-C-N-0-W-Z-A ¹ , Y

(Ii)

used at the head of the Table represents exactly the same compounds as the formula:

( I)

used earlier. The use of Formula (Ii) with the Table is intended to simplify the understanding of structures of compounds represented in that Table. Inspection of (Ii) and (I) will readily show that:

X ¹ -B of (Ii) is the same as G of (I),

Y of (Ii) is the same as X of (I), W-Z-A^ of (Ii) is the same as A of (I).

_ΓΔB E___I

X ¹ -B-C=N-0-W-Z-A ¹

CMPP X ^x B X H z. A ^x m.p.r C\

1 (Mβ) ₂ -N CO Cl CO NH 3,4-Cl-Ph 144-146

2 (Mβ) ₂ -N CO Cl CO NH Ph oil

3 (Me) ₂ -N CO Cl CO NH 2,4-Cl-Ph 137-138

4 ( e) ₂ -N CO Cl CO NH 2,5-Cl-Ph 155-157

5 (Me) ₂ -N CO Cl CO NH 3-Cl-Ph 85-96

6 ( β) ₂ -M CO Cl CO NH 4-Cl-Ph 123-129

7 (Me) ₂ -N CO Cl CO NH 3,5-Mβ-Ph 132-146

8 (Mβ) ₂ -N CO Cl CO NH 2,6-Cl-Ph 182-185

9 (Me) ₂ -N CO Cl CO NH 3-F-Ph lb

109-112

10 (Mβ) ₂ -N CO Cl CO NH 3-CF ₃ -Ph 128-132

11 (Mβ) ₂ -N CO Cl CO NH 3-N0 ₂ -Ph 159-163

12 (Me) ₂ -N CO Cl CO NH 3-0CH ₃ -Ph 70-80

13 (Me) ₂ -N CO Cl CO NH 1-naphthyl 126-128

14 (Me) ₂ -N CO Cl CO NH 2,4,5-Cl-Ph 184-186

15 (Me) ₂ -N CO Cl CO NH 3,5-CF ₃ -Ph 184-187

16 (Me) ₂ -N CO Cl CO NH 3,4-F-Ph 133

17 (Me) ₂ -N CO Cl CO NH 2,5-F-Ph 111-113

18 (Me) ₂ -N CO Cl CO NH 3,5-0CH ₃ -Ph 126-136

19 (Me) ₂ -N CO Cl CO NH 3,5-C0 ₂ CH ₃ -Ph 170-178

20 (Me) ₂ -N CO Cl CO NH 2,3-Cl-Ph 126-129

CMPP X ^J B W Δ ⁴ m.p.fC.

21 (Me) ₂ -N CO Cl CO NH 4-Br-Ph 143-145

22 (Me) ₂ -N CO Cl so ₂ - 3,5-Cl-Ph 75-78

26 (Me) ₂ -N CO Cl so ₂ - 4-Cl-Ph 153-155

27 (Mβ) ₂ -N CO Cl PO CH., (0-CH ₂ -C-Cl ₃ ) ₂ 88-90

28 (Me) ₂ -N CO Cl so ₂ - 4-Mβ-Ph 133-136

29 (Me) ₂ -N CO Cl so ₂ - 4-Br-Ph 134-136

30 OEt CO Cl so ₂ - 4-Br-Ph 82-84

31 OEt CO Cl so ₂ - 4-Cl-Ph 62-65

32 (Me) ₂ -N CO Cl CO NH 3-CN-Ph 175-179 lb

33 ( e) ₂ -N CO Cl CO NH 3-COCH ₃ -Ph 168-169 Ul

34 OEt CO Cl CO NH 3,5-Cl-Ph 152-154

35 NH ₂ CO Cl CO NH 3,5-Cl-Ph 224-226

36 (Me) ₂ -N CO Cl CO NH 3-S0 ₂ CH ₃ -Ph 156-161

37 (Me) ₂ -N CO Cl CO NH 3-SCH ₃ -Ph 116-119

38 (Mβ) ₂ -N CO Cl CO NH 2-Cl-Ph 104-107

39 ( e) ₂ -N CO Cl CO NHCH ₂ Ph 78-93

40 (Me) ₂ -N CO Cl CO - 3,5-Cl-Ph 92-95

41 (Me) ₂ -N CO Cl CO NH 4,6-Cl-2-pyrimidino 167-169

42 ( e) ₂ -N CO Cl CO NH 3,5-Cl-Ph 168-169

43 (Me) ₂ -N CO Cl CO NH Me 87-88

CMPD X ^x B H ffltgt (° C)

44 (Me) ₂ -N CO Cl CO NH 2 , 6-F-Ph 136-146

45 (Me) ₂ -N CO Cl CO NH 2-CF ₃ -Ph 116-118

46 (Mβ) ₂ -N CO Cl CO NH 2-N0 ₂ -Ph 130-134

47 (ME) ₂ -N CO Cl CO NH 2-Et-Ph 93-98

48 (Mβ) ₂ -N CO Cl CO NH •Z-OCHg-Ph 124-127

49 (Me) ₂ -N CO Cl CO NH 2-Mβ-Ph 114-118

50 (Me) ₂ -N CO Cl CO NH 4-OCH ₃ -Ph 112-116

51 (Mβ) ₂ -N CO Cl CO NH 3, 5-Cl-4-SCN-Ph 210-211

52 Et,Mβ-N CO Cl CO NH 3 , 4-Cl-Ph 123-126

53 Et,Mβ-N CO Cl CO NH 3-Cl-Ph 95-98

54 Et,Me-N CO Cl CO NH 3, 5-Cl-Ph 152-155

55 Et,Me-N CO Cl CO NH 2 , 6-Cl-Ph 142-145 lb en

56 Et,Mβ-N CO Cl CO NH 3-CF ₃ -Ph 112-114

57 Et,Mβ-N CO Cl CO NH 3 , 5-CF ₃ -Ph 143-145

59 pyrrolidino CO Cl CO 4-Cl-Ph 114-115

60 piperidino CO Cl CO - 4-Cl-Ph 84-86

61 (Me) ₂ -N CO Cl CO NH 3-Mβ-Ph 73-76

62 (Me) ₂ -N CO Cl CO NH 4-Mβ-Ph 101-104

63 (Mβ) ₂ -N CO Cl CO CH=CH Ph oil

64 (Mβ) ₂ -N CO Cl CO - 2 , 6-Me-Ph 88-89

CMPP X ^x B X H z. Δ m.p.CO

65 (Me) ₂ -N CO Cl CO CHC1 Ph oil

66 (Me) ₂ -N CO Cl CO - 2-furyl 79-81

67 (Me) ₂ -N CO Cl CO - 2-naphthyl 141-142

68 (Me) ₂ -N CO Cl CO - 1-naphthyl 93-95

69 (Me) ₂ -N CO Cl CO CH ₂ 1-naphthyl grease

70 pyrrolidino CO Cl CO NH 3-Cl-Ph 107-111

71 pyrrolidino CO Cl CO NH 3,5-Cl-Ph 150-152

72 pyrrolidino CO Cl CO NH 2,6-Cl-Ph 190

73 pyrrolidino CO Cl CO NH 3,4-Cl-Ph 137-140

74 piperidino CO Cl CO NH 3-Cl-Ph 118-120 dec

75 piperidino CO Cl CO NH 3,5-Cl-Ph 185-186

76 piperidino CO Cl CO NH 2,6-Cl-Ph 160-163 >

77 piperidino CO Cl CO NH 3,4-Cl-Ph 123-125

78 (Me) ₂ -N CO Cl CO NHCH ₂ 2-Cl-Ph 115-119

79 (Me) ₂ -N CO Cl CO NHCH ₂ 3,4-Cl-Ph 83-87

80 (Me) ₂ -N CO Cl CO NH 3,5-F-Ph 167-171

81 (Me) ₂ -N CO Cl CO NH 3,5-CN-Ph 195-198

82 (Me) ₂ -N CO Cl CO NH 4-CN-Ph 171-174

83 (Me) ₂ -N CO Cl CO NH 4-COCH ₃ -Ph 149-152

84 (Me) ₂ -N CO Cl CO - 4-0CH ₃ -Ph 115-116

85 (Me) ₂ -N CO Cl CO - 4-Cl-Ph 97-98

86 (Me) ₂ -N CO Cl CO - 3-Cl-Ph 100-101 87 (Me) ₂ -N CO Cl CO - 2-Cl-Ph 99-100 88 (Me) ₂ -N CO Cl CO - 4-CN-Ph 90-91 89 (Me) ₂ -N CO Cl CO - 4-N0 ₂ -Ph 104-105 90 (Me) ₂ -N CO Cl CO - 3-N0 ₂ -Ph 117-118 91 (Me) ₂ -N CO Cl CO - 2-N0 ₂ -Ph 88-89 92 (Me) ₂ -N CO Cl CO - 4-CF ₃ -Ph 105-106 93 (Me) ₂ -N CO Cl CO - 3-CF ₃ -Ph oil 94 (Me) ₂ -N CO Cl CO - 2-CF ₃ -Ph 86-87 95 (Me) ₂ -N CO Cl CO - 4-Me-Ph 98-101 96 (Me) ₂ -N CO Cl CO - 3-Me-Ph 73-75 97 (Me) ₂ -N CO Cl CO - 98 Me-NH CO Cl CO NH 99 Me-NH CO Cl CO NH 3,4-Cl-Ph 167-170 100 Me-NH CO Cl CO NH 3.5-Cl-Ph 185-190 101 Me-NH CO Cl CO NH 2,6-Cl-Ph >200 102 Me-NH CO Cl CO NH 3-CF ₃ -Ph 170-173 103 Me-NH CO CL CO NH 3,5-CF ₃ -Ph 195-100 104 (Me) ₂ -N CO Cl PO - (0-Ph) ₂ oil 105 (Me) ₂ -N CO Cl so ₂ - CH ₃ 54-58 106 (Me) ₂ -N CO Cl CO NH 2-C0 ₂ CH ₃ -Ph 118-122

CMPP X ¹ B X H Δ ¹ m.p.(°C)

107 (Me) ₂ -N CO Cl CO NH 44--ii--PPrr--PPhh 110022--110044

108 (Me) ₂ -N CO Cl CO NH 2-Me,6-Cl-Ph 160-166

109 (Me) ₂ -N CO Cl CO NH 4-C0 ₂ CH ₂ CH ₃ -Ph 147-148

110 (Me) ₂ -N CO Cl CO NH 3-N0 ₂ ,4-F-Ph 171-175

111 (Me) ₂ -N CO Cl CO NH 4-F-Ph 98-101

112 (Me) ₂ -N CO Cl CO NH 4-N0 ₂ -Ph 154-157

113 (Me) ₂ -N CO Cl CO NH 4-CF ₃ -Ph 123-129

114 (Me) ₂ -N CO Cl CO O 4-Me-Ph 93-94

115 (Me) ₂ -N CO Cl CO - 2-Me-Ph semi-solid

116 (Me) ₂ -N CO Cl CO - 2-0CH ₃ -Ph oil

117 (Me) ₂ -N CO Cl CO - 3-OCH ₃ -Ph oil

118 (Me) ₂ -N CO Cl CO NH 2-i_Pr-Ph 96-106 lb

VO

119 (Me) ₂ -N CO Cl CO NH 4-SCH ₃ -Ph 76-80

120 (Me) ₂ -N CO Cl CO NH 2-0CH ₃ ,4-NO ₂ -Ph 154-158

121 (Me) ₂ -N CO Cl CO - 3,5-CF ₃ -Ph 84-89

122 morpholino CO Cl CO NH 3,5-Cl-Ph 140-176

123 (Me) ₂ -N CO Cl CO NH 4-S0 ₂ CH ₃ -Ph 35-75

124 (Me) ₂ -N CO Cl CO - 2,6-Cl-Ph 113-116

125 (Me)-,-N CO Cl CO - Me 5_0_-5_5_

126 (Et),-N CO Cl CO NH 33--CCll--PPhh 111155--111166 ^c

CMPP X ¹ B X H z. Δ ¹ m.p. C C)

127 (Et) ₂ -N CO Cl CO NH 3,5-Cl-Ph 160-161

128 (Et) ₂ -N CO Cl CO NH 3.5-CF ₃ -Ph 154-160

129 (E f ₂ «N CO Cl CO NH •3,4-Cl-Ph 156-158

130 (Et) ₂ -N CO Cl CO NH 2,6-Cl-Ph 116-120

131 piperidino CO Cl CO NH 3.5-CF ₃ -Ph 157-161

132 piperidino CO Cl CO NH 3-CF ₃ -Ph oil

133 pyrrolidino CO Cl CO NH 3-CF ₃ -Ph 119

135 pyrrolidino CO Cl CO - 3-CF ₃ -Ph oil

136 Me-NH CO Cl CO - 4-N0 ₂ -Ph 156-160

137 Me-NH CO Cl CO - 4-CN-Ph 166-169

138 Me-NH CO Cl CO - 4-CF ₃ -Ph 126-129

139 Me-NH CO Cl CO - 2-CF ₃ -Ph 136-139 ui o

140 Me-NH CO Cl CO - 3-N0 ₂ -Ph 168-170

141 Me-NH CO Cl CO - 4-OCH ₃ -Ph 133-135

142 Me-NH CO Cl CO - 4-Me-Ph 125-127

143 Me-NH CO Cl CO - 4-Cl-Ph 135-137

144 Et,Me-N CO Cl CO - 4-N0 ₂ -Ph 85-88

145 Et,Me-N CO Cl CO - 4-CN-Ph 110-112

146 Et,Me-N CO Cl CO - 4-CF ₃ -Ph 53-56

CMPP X ¹ B X H Δ ¹ m.p.CC)

147 Et,Me-N CO Cl CO - 22--CCFF ₃₃ --PPhh ooiill

148 Et.Me-N CO Cl CO - 3-N0 ₂ -Ph 55-58

149 Et,Me-N CO Cl CO - 4-Me-Ph 50-52

150 Et,Me-N CO Cl CO - 4-Cl-Ph 83-85

151 (Me) ₂ -N CO Cl CO NHCH ₂ 4-Cl-Ph 105-108

152 (Me) ₂ -N CO Cl CO CH ₂ 2,6-Cl-Ph 118-120

153 (Me) ₂ -N CO Cl CO - 5-Me-2-thiophene 86-87.5

154 (Me) ₂ -N CO Cl CO - 5-Br-2-furan 66-68

155 (Me) ₂ -N CO Cl CO - 3-furan 47-49

156 (Me) ₂ -N CO Cl CO CH ₂ CH ₂ Ph oil

157 (Me) ₂ -N CO Cl CO CH ₂ Ph oil

158 (Me) ₂ -N CO Cl CO - 4-pyridine gum U

159 (Me) ₂ -N CO Cl CO - 3-pyridine gum

160 (Me) ₂ -N CO Cl CO - t-Bu 61.5-63

161 (Me) ₂ -N CO Cl CO - C(CH ₃ ) ₂ CH ₂ C1 oil

162 (Me) ₂ -N CO Cl CO NHCH ₂ 2-thiophene 113-116

163 (Me) ₂ -N CO Cl CO NHCH ₂ 3-Me-Ph oil

164 (Et) ₂ -N CO Cl CO NHCH ₂ 3,4-Cl-Ph 93-98

165 (Et) ₂ -N CO Cl CO NHCH ₂ 2-Cl-Ph 86-99

166 (Et) ₂ -N CO Cl CO NHCH ₂ 44--CCll--PPhh 7799--8822

CMPP» X ¹ fi X £_ z Δ ¹ m.p.CO

167 (Et) ₂ -N CO Cl CO NHCH ₂ 2-thiophene 74-77

168 (Et) ₂ -N CO Cl CO NHCH ₂ Ph 86-91

'169 (Me) ₂ -N CO Cl CO - 2-thiophene 90-93

170 (Et) ₂ -N CO Cl CO NHCH ₂ 3-Cl-Ph 78-82

171 (Me) ₂ -N CO Cl CO CH ₂ 2-thiophene oil

172 (Et) ₂ -N CO Cl CO - 3-Me-Ph oil

173 (Et) ₂ -N CO Cl CO - 3-CF ₃ -Ph oil

174 (Et) ₂ -N CO Cl CO - 3-N0 ₂ -Ph

175 (Et) ₂ -N CO Cl CO - 3-Cl-Ph oil

176 (Et) ₂ -N CO Cl CO - 3-OCH ₃ -Ph oil

177 (Et) ₂ -N CO Cl CO - 3-CN-Ph oil

178 (Et) ₂ -N CO Cl CO - 3,5-OCH ₃ -Ph oil Ul

179 piperidino CO Cl CO - 2-naphthyl 52-54

180 pyrrolidino CO Cl CO - 2-naphthyl 91

181 i-Pr,Me-N CO Cl CO - 2-naphthyl 87-92

182 (i-Pr) ₂ -N CO Cl CO NH 3,5-CF ₃ -Ph 182-189 dec

183 benzyl, Me-N CO Cl CO NH 3,5-CF ₃ -Ph 126-131

184 i-Pr,Me-N CO Cl CO NH 3,5-CF ₃ -Ph 147-148

185 pyrrolidino CO Cl CO NH 3,5-CF ₃ -Ph 158-161

CMPP X B Δ m.p. C' O

186 cyclohexyl,Me -N CO Cl CO NH 3,5-Cl-Ph 170-171

187 (Me) ₂ -N CO Cl CO - (CH ₂ ) ₅ -CH ₃ oil

188 (Me) ₂ -N CO Cl CO - (CH- )n-CH-i oil

189 (Me) ₂ -N CO Cl CO - * ^CH 2-'l2~ ^CH 3 60-62

190 (Me) ₂ -N CO Cl CO - ( ^CH 2-*16~ ^CH 3 43-45

191 (Me) ₂ -N CO Cl CO - p-biphenyl 124-127

192 piperidino CO Cl CO NH 3,5-F-Ph 169-172

193 pyrrolidino CO Cl CO NH 3,5-F-Ph 147-151 dec

194 (i-Pr) ₂ -N CO Cl CO NH 3,5-F-Ph 156-156.5

Ul

195 (Me) ₂ -N CO Cl CO - CHBrCH ₃ oil ω

197 - SPh Cl CO O Et oil

198 - SOPh Cl CO O Et oil

199 - S0 ₂ Ph Cl CO O Et 82-84

200 (Me) ₂ -N CO Cl CO O Et 40-44

201 OEt CO Cl CO O Et oil

202 (Me) ₂ -N so ₂ Cl CO 0 Et oil

203 (i-Pr) ₂ -N CO Cl CO NH 2,6-Cl-Ph 178-188 dec

204 (CH ₂ CH ₂ OCH ₃ ) ₂ - •N CO Cl CO NH 2,6-Cl-Ph gum

205 i-Pr,Me-N CO Cl CO NH 3,5-Cl-Ph 139-146

206 (i-Pr) ₂ -N CO Cl CO - 2-naphthyl 158-159

CMED X B X, H Z Δ ^x m.p.fC.

207 (CH ₂ CH ₂ 0CH ₃ ) ₂ -N CO Cl CO - 2-naphthyl 48-51

208 (Me) ₂ -N CO Br CO - Ph oil

209 (n-Bu) ₂ -N CO Cl CO NH 3,5-Cl-Ph 202-204

210 (n-Bu) ₂ -N CO Cl CO NH 3,5-CF ₃ -Ph 92-96

211 (n-Bu) ₂ -N CO Cl CO NH 3-Cl-Ph 194-196

212 (n-Bu) ₂ -N CO Cl CO NH 3,4-Cl-Ph 185-187

213 (Me) ₂ -N CO Cl CO - 2,6-Me-Ph 160-164

214 piperidino CO Cl CO - p-biphenyl 111-113

215 pyrrolidino CO Cl CO - p-biphenyl 123-126

216 n-Bu,Me-N CO Cl CO NH 3,5-Cl-Ph 108-113

217 3-Me-piperidino CO Cl CO NH 3,5-Cl-Ph 172-175

218 cyclohexyl,Me-N CO Cl CO NH 3,5-Cl-Ph 159-163 ui ιb

219 (CH ₂ CH ₂ OCH ₃ ) ₂ -N CO Cl CO NH 3,5-Cl-Ph 110-114

220 n-Bu,Me-N CO Cl CO NH 2,6-Cl-Ph 203-205 dec

221 i-Pr,Me-N CO Cl CO NH 2,6-Cl-Ph 192-197

222 cyclohexyl,Me-N CO Cl CO NH 2,6-Cl-Ph 212-216

223 pyrrolidino CO Cl CO NH 2,4,5-Cl-Ph 137-141 dec

224 piperidino CO Cl CO NH 2,4,5-Cl-Ph 121-122

225 (i-Pr) ₂ -N CO Cl CO NH 2,4,5-Cl-Ph 125-126

226 benzyl,Me-N CO Cl CO NH 2,4,5-Cl-Ph 128-130

227 cyclohexyl,Me -N CO Cl CO NH 2,4,5-Cl-Ph 111-117

228 (CH ₂ CH ₂ OCH ₃ ) ₂ -N CO Cl CO NH 2,4,5-Cl-Ph 102-105

229 n-Bu.Me-N CO Cl CO NH 3,5-CF ₃ -Ph 119-121

230 3-Me-ρiperidino CO Cl CO NH 3,5-CF ₃ -Ph 162-163

231 cyclohexyl.Me- -N CO Cl CO NH 3,5-CF ₃ -Ph 176-177

232 pyrrolidino CO Cl CO NH 2,3,4,5-Cl-Ph 152-155 dec

233 piperidino CO Cl CO NH 2.3,4,5-Cl-Ph 236

234 (Et) ₂ -N CO Cl CO NH 2,4,5-Cl-Ph 146-148

235 (Et) ₂ -N CO Cl CO - 2-naphthyl 81-82.5

236 (Me) ₂ -N CO Cl so ₂ - 4-N0 ₂ -Ph 114-118

237 piperidino CO Cl CO - 1-naphthyl 91-98

238 cyclohexyl,Me- -N CO Cl CO - 2-naphthyl 127-129 Ul Ul

239 (Me) ₂ -N CO Cl CO - 2-(l-Br-naphthyl) 96-100

240 t-Bu-NH CO Cl CO - 2-naphthyl 132-135

241 t-Bu-NH CO Cl CO NH 3.5-Cl-Ph 116-118

242 t-Bu-NH CO Cl CO NH 3,5-CF ₃ -Ph 167-168

243 t-Bu-NH CO Cl CO NH 2,4,5-Cl-Ph 234-239 dec

244 3,5-Me-piperidino CO Cl CO NH 3,5-Cl-Ph 176-178

246 (Me) ₂ -N CO Br CO - 2-naphthyl 128-130

CMPP X ^x fi H Δ ^x m.g.CC)

247 piperidino CO Cl CO NHCH ₂ 2-Cl-Ph oil

248 (Me) ₂ -N CO Cl CO NH CH(Ph) ₂ oil

249 (Me) ₂ -N CO Cl CO NH t-Bu 72-74

250 (Me) ₂ -N CO Cl CO NH cyclohexyl 76-79

251 (Me) ₂ -N CO Cl CO cyclohexyl 54-57

252 (Me) ₂ -N CO Cl CO o Bu oil

253 (Et) ₂ -N CO Cl CO 2-OCH ₃ -Ph

254 n-Bu,Me-N CO Cl CO 2 -naphthyl oil

255 piperidino CO Cl CO 2-(l-Br-naphthyl) 116-121

256 3-Me-piperidino CO Cl CO NH 2,4,5-Cl-Ph 106-108

257 i-Pr,Me-N CO Cl CO NH 2,4,5-Cl-Ph 210-214

258 3-Me-piperidino CO Cl CO NH 2,3,4,5-Cl-Ph 127-128 Ul

259 (Me) ₂ -N CO Cl CO OCH _j Ph 84-86

260 (Me) ₂ -N CO Cl CO 0 CH ₃ 56-69

261 (Me) ₂ -N CO Cl CO NH 2,6-i-Pr-Ph 172-174

262 (Me) ₂ -N CO Cl CO 0 allyl oil

263 (Me) ₂ -N CO Cl CO NH 2,6-Et-Ph 128-130

264 (Me) ₂ -N CO Cl CO NH 2,4,6-Me-Ph 99-100

265 (Me) ₂ -N CO Cl CO 3-S0 ₂ Cl-Ph 119-120

266 O-i-Pr CO Cl CO 2 -naphthyl 85-87

267 O-i-Pr CO Cl CO 4-Cl-Ph 180-182

CMPP X ^x B H Δ ^x m.p. CO

268 O-i-Pr CO Cl CO 4-Br-Ph 201-203

269 O-i-Pr CO Cl CO 3,5-Cl-Ph 91-93

270 OEt CO Cl CO 2 -naphthyl 96-96.5

271 OEt CO Cl CO 4-Cl-Ph 110-112

272 OEt CO Cl CO 4-Br-Ph 110-112

273 OEt CO Cl CO 3,5-Cl-Ph 87-88

276 O-t-Bu CO Cl CO 4-Cl-Ph 84-86

277 O-t-Bu CO Cl CO 4-Br-Ph 83-85

278 O-t-Bu CO Cl CO 3,5-Cl-Ph 150-152

279 Me CO Cl CO 2 -naphthyl 145-147

280 Me CO Cl CO 4-Cl-Ph 112-116

281 Me CO Cl CO 4-Br-Ph 136-138

282 Me CO Cl CO 3,5-Cl-Ph 104-106

283 Ph CO Cl CO 4-Cl-Ph 145-147

284 Ph CO Cl CO 4-Br-Ph 138-140

285 Ph CO Cl CO 3,5-Cl-Ph 99-101

286 O-t-Bu CO Cl CO 2 -naphthyl 97-99

287 azetidino CO Cl CO 2 -naphthyl 139-141

CMPP X ^J fi X H Z Δ ^x m.p. (° C)

288 3-Me-piperidino CO Cl CO - 2-naphthyl oil

289 3.5-Me-piperidino CO Cl CO - 2-naphthyl oil

290 homopiperidino CO Cl CO - 2-naphthyl oil

291 benzyl,Me-N CO Cl CO - 2-naphthyl gum

292 HH ₂ CQ Cl CO - 2-naphthyl 178-180

293 pyrrolidino CO Cl CO - 2-(l-Br-naphthyl) 119-123

294 azetidino CO Cl CO NH 3 _. 5-Cl-Ph 184-185

295 homopiperidino CO Cl CO NH 3,5-Cl-Ph 169-171

296 i-Pr-NH CO Cl CO NH 3,5-Cl-Ph 221-227

297 piperidino CO Cl CO - '9-fluorenyl 175-177 dec

298 piperidino CO Cl CO - 4-OCH ₃ -Ph 87-93

299 pyrrolidino CO Cl CO - 4-OCH ₃ -Ph 74-76 U 0

300 piperidino CO Cl CO - 3-(6-Cl)pyridine) 134-135

301 (Me) ₂ -N CO Cl CO - 3-(6-Cl-pyridine) 111-112

302 piperidino CO Cl CO - 2-fluoren-9-onyl 129-132

303 (Me) ₂ -N CO Cl CO - 2-fluoren-9-onyl 153-154

304 (Me) ₂ -N CO Cl CO - 9-anthracenyl 176-182

305 (Me) ₂ -N CO Cl CO NH 4-NH ₂ » HCl-Ph 209 dec

306 (Me) ₂ -N CO Cl CO NH 4-C0 ₂ H-Ph 199-200

307 (Me) ₂ -N CO Cl CO - Ph 60-64

CMPP X ^x fi X H z Δ ¹ m.p. f° Q

308 (Me) ₂ -N CO Cl CO - 4-S0 ₂ Cl -Ph 91-93

309 (Me) ₂ -N CO Cl CO - 4-NH ₂ HBr H _z O-Ph 210 dec

310 (Me) ₂ -N CO Cl CO - 4-NH ₂ -Ph 153-154

311 (Me) ₂ -N CO Cl CO - 3-S0 ₂ NH ₂ -Ph 170-173

312 (Me) ₂ -N CO Cl CO - 2-C0 ₂ -t-Bu-Ph 86-89

313 - SCH ₂ Ph Cl CO NH 3,5-Cl-Ph 98-102

314 - SCH ₂ Ph Cl CO NH 3,4-Cl-Ph <50

315 - SCH ₂ Ph Cl CO NH 3-Cl-Ph 88-92

316 (Me) ₂ -N CO Cl CO - S-n-Bu oil

317 (Me) ₂ -N CO Cl CO - o-biphenyl 68-72

318 (Me) ₂ -N CO Cl CO - 4-O-cHexyl-Ph 90-92

319 (Me) ₂ -N CO Cl CO - 3-quinolinyl 111-114

320 piperidino CO Cl CO - 3-guinolinyl 101-103

321 (Me) ₂ -N CO Cl CO NH 3,5-Cl-Ph 156-157

322 t-Bu-NH CO Cl CO NH 2,6-Cl-Ph 234 dec

323 n-Pr-NH CO Cl CO - 2-naphthyl 138-139

324 (Me) ₂ -N CO Cl CO - 9-phenanthracenyl 129

325 piperidino CO Cl CO - 9-phenanthracenyl 99-100

326 (Me) ₂ -N Co Cl CO C C((CCH-,), 4-Cl-Ph oil

327 piperidino CO Cl CO C C((CCH ₃ ) ₂ 4-Cl-Ph oil

328 piperidino CO Cl CO - 9-anthracenyl 169-181

fa 1 A rH en A fa

&1 A fa A U A 1 fl A A fa CJ fa 1 fa rt A φ A fa A A CU A 1 1 1 tn 1 CJ X! fa J3 A

A fa 1 CU fa 1 fa φ tn rrt fa rt 1 fa 1 fa U

CU 1 cn 1 1 cn 1 2 J CJ CJ tn 1 en I 1

-rt _S fa rt φ af irt 1 rH 1 I 1 % φ fa rt φ

A 2 J J 2 CJ J to U to in •*• cn 2 CJ CJ 2 rt I A 1 1 1 1 1 1 _* 1 _* % «_ A 1 1 1 1 u u fM <M CM ro cn cn CM fM CN ro cn CM fa CM CM CM ro

X X X X X X X X X X X X X H z z z z z z z z z z z z z g a o o σ o o o o d d d d d d d d d d d o

CJ CJ CJ CJ CJ CJ CJ CJ CJ CJ CJ CJ CJ CJ CJ CJ CJ CJ CJ rt rt rt rt rt rt rt rt rt rt rt rt rt rt rt rt rt rt rt

M cj u c υ c cj c c c c cj cj u c cj cj cj cj cj

031 o CJ oCJ oCJ oCJ oCJ oCJ dU dCJ dCJ dCJ dCJ dCJ dCJ dCJ dCJ dCJ dCJ dCJ dCJ

X ¹ B X H z Δ ¹

Me-NH CO Cl CO NH 2,6-Me-Ph

Me-NH CO Cl CO NH 2-Cl,5-CF ₃ -Ph

Me-NH CO Cl CO NH 2,3-Cl-Ph

(Me) ₂ -N CO Cl CO NH 2-Cl-Ph

C1CH ₂ CH ₂ -NH CO Cl CO NH 2-Cl-Ph

(Me) ₂ -N CO Cl CO CH ₂ 3-Cl-Ph sec-Bu-NH CO Cl CO NH 3-Cl-Ph orpholino CO CL CO NH 3-Cl-Ph n-Bu,Me-N CO Cl CO NH 4-Cl-Ph

(Me) ₂ -N CO Cl CO NH 3-I-Ph

(Me) ₂ -N CO Cl CO NH 4-SCN-Ph

(Me) ₂ -N CO Cl CO CH ₂ 2-Me-Ph .

(Me) ₂ -N CO Cl CO CHMe 2-Me-Ph

o o O o o a J CJ CJ u CJ o CJ C oJ CoJ oCJ oCJ oCJ oCJ oCJ CoJ oCJ oCJ CoJ oCJ irt rt trt rt rrt •rt rt trt

X V J υ CJ CJ υ CJ u CJ CJ υ CJ o O o σ o a* CJ J CJ CJ CJ o CJ o CJ ou oCJ oCJ oυ oJ oCJ oj oCJ oJ oJ oJ

fl H Δ ^J

3-Me0-benzyl-NH CO Cl CO NH 2-N0 ₂ -Ph

(Me) ₂ -N CO Cl CO NH 3-N0 ₂ -benzyl

(Me) ₂ -N CO Cl CO NH 4-N0 ₂ -Ph

(Me) ₂ -N CO Cl CO NH 3-C0 ₂ CH ₂ CH ₂ Cl-Ph

(Me) ₂ -N CO Cl CO NH 3-CONMe ₂ -Ph

(Me) ₂ -N CO Cl CO NH 3-CO(4-morpholino)-Ph

(Me) ₂ -N CO Cl CO NH 3-NMe ₂ -Ph

(Me) ₂ -N CO Cl CO NH 3-SEt-Ph

(Me) ₂ -N CO Cl CO NH 2-SCH ₂ CF ₃ -Ph

(Me) ₂ -N CO Cl CO NH 2-S0 ₂ Me-Ph

(Me) ₂ -N CO Cl CO NH 2-S0 ₂ NMe ₂ -Ph

(Me) ₂ -N CO Cl CO NH 3-S0 ₂ NMe ₂ -Ph

(Me) ₂ -N CO Cl CO NH 4-S0 ₂ NMe ₂ -Ph

3-NC-Ph-NH CO Cl CO NH 2, 4-Cl-Ph

Et,Me-N CO Cl CO - 2, 6-Cl-Ph

(Me) ₂ -N CO Cl CO NH 2, 6-Cl-Ph

64

A A A X! A X! A X3 X! X3 A X! X3 X! A X! xs s A fa fa cu _| fa fa af fa fa fa fa fa CU fa fa fa fa | cu af fa

1 1 rt rH trt rt rt trt rt irt rt rt rt rt rt rt rt rt trt rt irt rt

CJ U U J CJ U CJ CJ J CJ CJ 1 u 1 U | CJ CJ CJ CJ CJ J CJ to to ^• -* •* •# ^• -v tn m tn in in in tn in m in fM cn ro cn en en cn cn cn cn cn en en en en m en en

X fM CJ _g

NH M B X X X X X X X X X X X

1 g X J z z § z Z z z z CJ z 1 CJ z

a o O O O O O O O O O O O O O d d d d d u o CJ CJ CJ CJ CJ CJ CJ CJ CJ CJ CJ CJ CJ CJ CJ CJ CJ CJ CJ

* _* «' rt rt rt rt rt

M CJ υ CJ CJ CJ CJ CJ CJ CJ CJ CJ CJ

Φ φ Φ

Φ xs

2 fa e ϋ n d d d d d d d d d d d O d d d d d d d d

OH J CJ J CJ CJ CJ CJ u CJ CJ CJ CJ O O CJ J O O CO CJ

fl Δ ^J

(Me) ₂ -N CO Cl CO NH 3-Cl,5-CN-Ph

(Me) ₂ -N CO Cl CO NH 3-Cl,5-COCH ₃ -Ph

(Me) ₂ -N CO Cl CO NH 2-Cl,4-Me-Ph

(Me) ₂ -N CO Cl CO NH 3-Cl,4-Me-Ph

(Me) ₂ -N CO Cl CO NH 3-Cl,5-Me-Ph

(Me) ₂ -N CO Cl CO NH 4-Cl,2-Me-Ph

(Me) ₂ -N CO Cl CO NH 5-Cl,2-Me-Ph

(Me) ₂ -N CO Cl CO NH 2-Cl,4-N0 ₂ -Ph

(Me) ₂ -N CO Cl CO NH 2-Cl,5-N0 ₂ -Ph

(Me) ₂ -N CO Cl CO NH 3-Cl,5-N0 ₂ -Ph

(Me) ₂ -N CO Cl CO NH 4-Cl,2-N0 ₂ -Ph

(Me) ₂ -N CO Cl CO NH 4-Cl,3-N0 ₂ -Ph

(Me) ₂ -N CO Cl CO NH 5-Cl,2-N0 ₂ -Ph

(Me) ₂ -N CO Cl CO NH 2-Cl,5-CF ₃ -Ph

(Me) ₂ -N CO Cl CO NH 3-Cl,5-CF ₃ -Ph

(Me) ₂ -N CO Cl CO NH 4-Cl,3-CF ₃ -Ph

(Me) ₂ -N CO Cl CO NH 2,3-Me-Ph

(Me) ₂ -N CO Cl CO NH 2,4-Me-Ph

s A s X3 A s xs X! XS xi A s S xs xs S X3

A s cu fa af fa fa fa fa fa cu fa fa cu fa fa cu fa fa 1 1 1 1 1 1 1 1 1 1 1 fa fa

1 1 1 1 1 1

1 1 φ Φ IN CN IN Z en en en cn cn ro tn m ro cn ro φ φ 2 2 d d d CJ fa fa fa fa fa fa fa fa fa fa fa

2 2 CJ

_I O d z U J u CJ

1 I z z U J

I 1 U u I | in rf tn ^■ tf to tn jl tn in in tn in in m m in in in fM CM fM CM

CM

X g X X X X z X X X X 33 X

NH § § z z z z § CJ z z z Z z d d d d d d d d d d d d d d d d d d d a u CJ u CJ CJ J u CJ CJ CJ CJ CJ CJ CJ CJ CJ CJ CJ CJ rt rt rt irt irt

M CJ CJ CJ CJ CJ CJ CJ CJ

φ 2

CM d d d d d d d d d O d d d d d d d d d J J CJ υ CJ CJ CJ CJ CJ CJ CO J CJ u CJ CJ CJ u CJ

XI

B H Δ ^J

(Me) ₂ -N CO Cl CO NH 2-Me,4-MeO-Ph

(Me) ₂ -N CO Cl CO NH 5-Me,2-OMe-Ph

(Me) ₂ -N CO Cl CO NH 2-Me,3-N0 ₂ -Ph

(Me) ₂ -N CO Cl CO NH 2-Me,4-N0 ₂ -Ph

(Me) ₂ -N CO Cl CO NH 2-Me,5-N0 ₂ -Ph

(Me) ₂ -N CO Cl CO NH 2-Me,6-N0 ₂ -Ph

(Me) ₂ -N CO Cl CO NH 3-Me, 5-N0 ₂ -Ph

(Me) ₂ -N CO Cl CO NH 4-Me,2-N0 ₂ -Ph

(Me) ₂ -N CO Cl CO NH 4-Me,3-N0 ₂ -Ph

(Me) ₂ -N CO Cl CO NH 2-OMe,5-N0 ₂ -Ph

(Me) ₂ -N CO Cl CO NH 4-OMe,2-N0 ₂ -Ph

(Me) ₂ -N CO Cl CO NH 2-N0 ₂ ,4-CF ₃ -Ph

(Me) ₂ -N CO Cl CO NH 4-N0 ₂ ,2-CF ₃ -Ph

(Me) ₂ -N CO Cl CO NH 4-N0 ₂ ,3-CF ₃ -Ph

(Me) ₂ -N CO Cl CO NH 5-N0 ₂ ,3-CF ₃ -Ph

(Me) ₂ -N CO Cl CO NH 4-SCN-Ph

(Me) ₂ -N CO Cl CO NH 2,4,6-Br-Ph

(Me) ₂ -N CO Cl CO NH 2,3,4-Cl-Ph

(Me) ₂ -N CO Cl CO NH 2,3,5-Cl-Ph

trt

X HJ S3 X X

NH z z z z z X SJ z z z X X z z X X X

1 z z z X X z X z X z

a o CJ oCJ oCJ oCJ oCJ oCJ oCJ oCJ o CJ oCJ oCJ oCJ oCJ oCJ oCJ oCJ oCJ oCJ oCJ rt rt rt rt rt

M CJ CJ CJ CJ CJ CJ CJ CJ CJ U

O O d d d d d d d d d d d d d d d CJ J CJ CJ J υ CJ CJ CJ CJ α CJ cj CJ CJ u CJ o CJ dCJ

z l z l z I z l z l z l z I z I z I z l z l z l z i z l z I z l z l z i z l

CN CM fM CM CM fM CM CM CN CM CM CN CM fM CM eN fM eN CN

Φ Φ Φ Φ Φ Φ Φ Φ Φ Φ Φ Φ Φ Φ Φ Φ Φ Φ Φ 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2

X)

X ¹ B X w z Δ ¹

(Me) ₂ -N CO Cl CO NH allyl

(Me) ₂ -N CO Cl CO NH l-(2-Cl-naphthyl)

(Me) ₂ -N CO Cl CO NH l-(3-Cl-naphthyl)

(Me) ₂ -N CO Cl CO NH l-(4-Br-naphthyl)

(Me) ₂ -N CO Cl CO NH l-(2-Me-naphthyl)

(Me) ₂ -N CO Cl CO NH l-(4-CN-naphthyl)

(Me) ₂ -N CO Cl CO NH 1-(2-OMe-naphthyl)

(Me) ₂ -N CO Cl CO NH l-(4-OMe-naphthyl)

(Me) ₂ -N CO Cl CO NH 1-(7-OMe-naphthyl)

(Me) ₂ -N CO Cl CO NH l-(2,4-Cl-naphthyl)

(Me) ₂ -N CO Cl CO NH 2-naphthyl)

(Me) ₂ -N CO Cl CO NH 2-(1-N0 ₂ -naphthyl)

(Me) ₂ -N CO Cl CO NH 2-(3-OMe-naphthyl)

(Me) ₂ -N CO Cl CO NH 2-(5-0Me-naphthyl)

(Me) ₂ -N CO Cl CO NH 2-(7-0Me-naphthyl)

(Me) ₂ -N CO Cl CO CH ₂ 2-naphthyl

(Me) ₂ -N CO Cl CO NH 2-furan

(Me) ₂ -N CO Cl CO NH 2-thiophene

(Me) ₂ -N CO Cl CO NH 2-(l-Me-pyrrole)

fi H Δ ^J

(Me) ₂ -N CO Cl CO NH 2-(l-Me-imidazole)

(Me) ₂ -N CO Cl CO NH 2-oxazole

(Me) ₂ -N CO Cl CO NH 2-thiazole

(Me) ₂ -N CO ci , CO NH 5-(l-Me-2-C0 ₂ Me-pyrazole)

(Me) ₂ -N CO Cl CO NH 4-(l,3-Me-5-Cl-pyrazole)

(Me) ₂ -N CO Cl CO NH 4-(l,3-Me-5-CN-pyrazole)

(Me) ₂ -N CO Cl CO NH 5-(l-Me,4-CONMe ₂ -pyrazole)

(Me) ₂ -N CO Cl CO NH 5-(l-Me.4-S0 ₂ NMe ₂ -pyrazole)

(Me) ₂ -N CO Cl CO NH 5-(l-Me,4-N0 ₂ -pyrazole) -4 o

(Me) ₂ -N CO Cl CO NH 4-(l-Me,5-Cl-pyrazole)

(Me) ₂ -N CO Cl CO NH 2-( ,6-OMe-pyrimidine)

(Me) ₂ -N CO Cl CO NH 2-(4-OCF ₃ ,6-Me-s-triazine)

(Me) ₂ -N CO Cl CO NH 2-(4-NMe ₂ , 6-OEt-s-triazine)

(Me) ₂ -N CO Cl CO NH 2-(4, 6-Cl-s-triazine)

(Me) ₂ -N CO Cl CO NH 3-pyridine

(Me) ₂ -N CO Cl CO NH 2-(4, 6-Cl-pyridine)

(Me) ₂ -N CO Cl CO NH 2-( 3 , 5, 6-Cl-l, 4-pyrazine)

(Me) ₂ -N CO Cl CO NH 3-(6-OMe-pyridine)

(Me) ₂ -N CO Cl Me ₂ -PO -

X

Nl 1 1 1 1 1 CJ 1 1 1 1 1 1 1 1 o fa

X

CJ

X

CJ rt O O υ | fa

4J a A O O O s o o o o o o O O o o o O O w fa fa fa fa fa u CJ CJ CJ CJ CJ CJ u CJ J o CJ υ rt rH rH irt rt irt kl irt rt rt rt rt irt rt trt kl rH •rt

M CJ CJ CJ J J CJ X CQ CJ α CJ CJ J CJ CJ J CD. CJ cj fM

O O O O O o o O o o o O o CO O O O o

001 CJ CJ J CJ CJ J J J CJ CJ J J O CJ CJ 1 CJ J CJ

XI

B H Δ ^J

Me ₂ -N CO Cl CO 5-quinoline pyrrolidine CO Cl CO 2-(3-Cl-thianaphthene) piperidine CO Cl CO 2-(7-Cl-benzofuran)

Me ₂ -N CO Cl CO 2-(7-OMe-benzofuraή)

Et ₂ -N CO Cl CO 2-(5-nitrobenzofuran)

Bu,Me-N CO Cl CO 2-(5-Cl-banzofuran) pyrrolidine CO Cl CO 2-(6,7(OMe) ₂ benzofuran) piperidine CO Cl CO 2-(3-Me-benzofuran)

Me ₂ -N CO Cl CO 2-(5-OMe-indole) to

Me ₂ -N CO Cl CO 2-azetidine pyrrolidine CO Cl CO 2-piperidine piperidine CO Cl CO 3-piperidine

E O CO Cl CO 4-piperidine

Me ₂ -N cs Cl CO 2-(2-meth lpiperidine) phenyl CO Cl CO 2-pyrrolidine butyl CO Cl CO 2-(2-methylpyrrolidine)

-CN - Cl CO 2-homopiperazine phenyl so ₂ Cl CO 3-morpholine

Me ₂ -N so ₂ Cl CO 2-tetrahydrothiophene

fl H Δ ^J

Bu,Me-N CO Cl CO 2- -(1,3-dithiane)

Me ₂ -N CO Br CO 2- -(1,3-dithiolane) pyrrolidine CO Cl CO 4- -thiazolidine

Me ₂ -N CO Cl so ₂ CF ₃ pyrrolidine CO Cl so ₂ butyl piperidine CO Cl so ₂ 2, ,5-Cl ₂ -Ph

Me ₂ -N cs Cl so ₂ 4- -CF ₃ -Ph

Ph CO Cl so ₂ 2,4,5-Cl ₃ -Ph

BuO CO Cl so ₂ 3-NH ₂ ,4-Cl-Ph

10

NC - Cl so ₂ 3-OCH ₃ -Ph phenyl so ₂ Cl so ₂ 4-Ph-Ph

Me ₂ -N so ₂ Cl so ₂ 2,4(N0 ₂ ) ₂ -Ph

Me ₂ -N CO Br so ₂ 2-naphthalene

Me ₂ -N CO Cl CO 5-piperonene piperdine CO Cl CO 2-(l,2,3,4-tetrahydronaphthalene) pyrrolidine CO Cl CO 2-(1 ,4-benzodioxane) butyl CO Cl CO 6-( l,4-benzodioxane)

Ph so ₂ Cl CO 6-chromane i-Pr-0 CO Cl CO 8-chromane

Et ₂ N CO Cl CO 5-( l, 2 , 3 , 4-tetrahydronaphthalene)

58

fl H k ¹

(Me) ₂ -N CO Cl CO - ^C 20 ^H 41

(Me) ₂ -N CO Cl CO NH ^C 20 ^H 41

(Me) ₂ -N CO Cl CO - CH=CH ₂

(Me) ₂ -N CO Cl CO NH Cri ₉ CHsCH

(Me) ₂ -N CO Cl CO - CH= ^* CH(CH ₂ ) ₁₇ CH ₃

(Me) ₂ -N CO Cl CO NH CH ₂ CH=CH(CH ₂ ) ₁₆ CH ₃

(Me) ₂ -N CO Cl CO - CΞCH

(Me) ₂ -N CO Cl CO NH CH^C^JCH

(Me) ₂ -N CO Cl CO - C zC(CH -) ^*"ι

(Me) ₂ -N CO Cl CO NH CH ₂ C=C(CH ₂ ) ₁₆ CH ₃ •b.

(Me) ₂ -N CO Cl CO - cyclopropyl

(Me) ₂ -N CO Cl CO NH cyclopropyl

(Me) ₂ -N CO Cl CO - cycloheptyl

(Me) ₂ -N CO Cl CO NH cycloheptyl

(Me) ₂ -N CO Cl CO - CH ₂ OMe

(Me) ₂ -N CO Cl CO NH CH ₂ CH ₂ OMe

(Me) ₂ -N CO Cl CO - CH ₂ 0(CH ₂ ) ₅ CH ₃

(Me) ₂ -N CO Cl CO - CHC1 ₂

(Me) ₂ -N CO Cl CO - CH ₂ CH ₂ SMe

X ^J fl H Δ ^J

(Me) ₂ -N CO Cl CO - CH ₂ S(CH ₂ ) ₅ CH ₃

(Me) ₂ -N CO Cl CO CH ₂ cyclopropyl

(Me) ₂ -N CO Cl CO CH ₂ cyclohexyl

(Me) ₂ -N CO Cl CO CH ₂ CN

(Me) ₂ -N CO Cl CO CH ₂ 4-Cl-Ph

(Me) ₂ -N CO Cl CO CH ₂ 4-F-Ph

(Me) ₂ -N CO Cl CO CH ₂ 4-Br-Ph

(Me) ₂ -N CO Cl CO CH ₂ 2,4,6-Cl-Ph

(Me) ₂ -N CO Cl CO CH ₂ 4-Me-Ph

(Me) ₂ -N CO Cl CO CH ₂ 3-CF ₃ -Ph

(Me) ₂ -N CO Cl CO CH ₂ 4-OMe-Ph

(Me) ₂ -N CO Cl CO CH ₂ 4-CN-Ph

(Me) ₂ -N CO Cl CO CH ₂ 4-SMe-Ph

(Me) ₂ -N CO Cl CO CH ₂ 4-S0 ₂ Me-Ph

(Me) ₂ -N CO Cl CO CH ₂ 4-NMe ₂ Ph

(Me) ₂ -N CO Cl CO CH ₂ 4-NH ₂ -Ph

(Me) ₂ -N CO Cl CO CH ₂ 4-Ph-Ph

(Me) ₂ -N CO Cl CO CH ₂ 4-OPh-Ph

(Me) ₂ -N CO Cl CO NH 4-CH ₂ CH ₂ Cl-Ph

B H Δ ^J

(Me) ₂ -N CO Cl CO NH 4-tOEt-Ph

(Me) ₂ -N CO Cl CO NH 4-CH ₂ CH=CH ₂ -Ph

(Me) ₂ -N CO Cl CO NH 4-CH ₂ CH=CHCH ₂ Cl-Ph

(Me) ₂ -N CO Cl CO NH 4-CH ₂ CΞCH-Ph

(Me) ₂ -N CO Cl CO NH 4-o-cyclohexyl-Ph

(Me) ₂ -N CO Cl CO NH 4-cyclohexyl-Ph

(Me) ₂ -N CO Cl CO NH 4-S0 ₂ F-Ph

(Me) ₂ -N . CO Cl CO NH 4-S0 ₃ CH ₂ CF ₃ -Ph

(Me) ₂ -N CO Cl CO NH 4-(4-pyridyl)-Ph

(Me) ₂ -N CO Cl CO NH 4-OPh-Ph

(Me) ₂ -N CO Cl CO NH 4_(4_C1-Ph)-Ph

(Me) ₂ -N CO Cl CO NH 4-OBu-Ph

(Me) ₂ -N CO Cl CO - 4-OBu-Ph

(Me) ₂ -N CO Cl CO - 4-CH ₂ CH ₂ Cl-Ph

(Me) ₂ -N CO Cl CO - 4-OEt-Ph

(Me) ₂ -N CO Cl CO - 4-CH ₂ CH=CH ₂ -Ph

(Me) ₂ -N CO Cl CO - 4-CH ₂ CH=CH ₂ CH ₂ Cl-Ph

(Me) ₂ -N CO Cl CO - 4-CH ₂ C≡CH-Ph

(Me) ₂ -N CO Cl CO - 4-cyclohexyl-Ph

B H Δ ^J

(Me) ₂ -N CO Cl CO 4-S0 ₂ F-Ph

(Me) ₂ -N CO Cl CO 4-S0 ₃ CH ₂ CF ₃ -Ph

(Me) ₂ -N CO Cl CO 4-(4-pyridyl) -Ph

(Me) ₂ -N CO Cl CO 4-OPh-Ph

(Me) ₂ -N CO Cl CO 4-(4-Cl-Ph) -Ph

(Me) ₂ -N CO Cl CO - 2-(6-Me-naphthyl)

(Me) ₂ -N CO Cl CO - 4-C0 ₂ CH ₂ CH ₂ Cl-Ph

(Me) ₂ -N CO Cl CO - 4-C0 ₂ CH ₂ OMe-Ph

(Me) ₂ -N CO Cl CO - 4-C0 ₂ CH ₂ C≡CCH ₂ C1-Ph

(Me) ₂ -N CO Cl CO - 4-C0 ₂ CH ₂ Ph-Ph

(Me) ₂ -N CO Cl CO - 4-OCH ₂ Ph-Ph

(Me) ₂ -N CO Cl CO - 3-CONHMe-Ph

(Me) ₂ -N CO Cl CO 0 (CH ₂ ) _lg -CH ₃

(Me) ₂ -N CO Cl CO 0 CH ₂ CH=CH(CH ₂ ) _lfi CH ₃

(Me) ₂ -N CO Cl CO 0 CH ₂ C=CH

(Me) ₂ -N CO Cl CO 0 CH C^C ( CH ) ι cCHα

(Me) ₂ -N CO Cl CO 0 Me

(Me) ₂ -N CO Cl CO 0 4-cyclohexyl -Ph

x ^x B X M z Δ ^A

(Me) ₂ -N CO Cl CO 0 (CB ₂ ) ₂ QMe

(Me) ₂ -N CO Cl CO 0 (CH ₂ ) ₂ C1

(Me) ₂ -N CO Cl CO 0 (CH ₂ ) ₂ SMePh

(Me) ₂ -N CO Cl CO 0 CH ₂ -cyclopropyl

(Me) ₂ -N CO Cl CO 0 CH ₂ -cyclohexyl

(Me) ₂ -N CO Cl CO 0 CH ₂ CH ₂ CN

(Me) ₂ -N CO Cl CO 0 (CH ₂ ) ₈ C1

(Me) ₂ -N CO Cl CO 0(CH ₂ ) ₂ Ph

(Me) ₂ -N CO Cl CO OCH ₂ 4-Me-Ph

(Me) ₂ -N CO Cl CO OCH ₂ 4-Cl-Ph

(Me) ₂ -N CO Cl CO OCH ₂ 4-F-Ph 00

(Me) ₂ -N CO Cl CO OCH ₂ 4-N0 ₂ -Ph

(Me) ₂ -N CO Cl CO OCH ₂ 3-CF ₃ -Ph

(Me) ₂ -N CO Cl CO OCH ₂ 3-CN-Ph

(Me) ₂ -N CO Cl CO OCH ₂ 4-OMe-Ph

(Me) ₂ -N CO Cl CO OCH ₂ 4-SMe-Ph

(Me) ₂ -N CO Cl CO OCH ₂ 4-S0 ₂ Me-Ph

(Me) ₂ -N CO Cl CO OCH ₂ 4-NMe ₂ -Ph

(Me) ₂ -N CO Cl CO OCH ₂ 4-NH ₂ -Ph

X ¹ 1 X w z Δ ¹ m.p. r o

(Me) ₂ -N CO Cl CO OCH ₂ 4-OPh-Ph

(Me) ₂ -N CO Cl CO s Me

(Me) ₂ -N CO Cl CO s (CH ₂ ) _lg CH ₃

(Me) ₂ -N CO Cl CO SCH ₂ Ph

(Me) ₂ -N CO Cl CO SCH ₂ 4-Cl-Ph

(Me) ₂ -N CO Cl CO OCH ₂ 4-Ph-Ph 142-143

(Me) ₂ -N CO Cl CO OCH ₂ 4-OPh-Ph

(Pr) ₂ -N CO Cl CO NH 3,5-Cl-Ph

(Pr) ₂ -N CO Cl CO NH 3,5-F-Ph

(Pr) ₂ -N CO Cl CO - 2-naphthyl t

(Pr) ₂ -N CO Cl CO - 4-CN-Ph

(Pr) ₂ -N CO Cl CO - p-biphenyl

Pr,Me-N CO Cl CO NH 3,5-Cl-Ph

(Pr) ₂ -N CO Cl CO NH 3,5-Cl-Ph

(Pr) ₂ -N CO Cl CO NH 3,5-F-Ph

(Pr) ₂ -N CO Cl CO - 2-naphthyl

(Pr) ₂ -N CO Cl CO - 4-CN-Ph

(Pr) ₂ -N CS Cl CO - p-biphenyl

Pr,Me-N CO Cl CO NH 3,5-Cl-Ph

Pr,Me-N CO Cl CO NH 3,5-F-Ph

Pr,Me-N CO Cl CO - 2-naphthyl

Pr,Me-N CO Cl CO - 4-CN-Ph

X ^J B H Δ ^J

Pr,Me-N CO Cl CO - p-biphenyl

-N-Me,CH ₂ CH ₂ CH ₂ Cl CO Cl CO NH 3,5-Cl-Ph

-N-Me,CH ₂ CH ₂ CH ₂ Cl CO Cl CO NH 3,5-F-Ph

-N-Me,CH ₂ CH ₂ CH ₂ Cl CO Cl CO - 2-naphthyl

-N-Me,CH ₂ CH ₂ CH ₂ C1 CO Cl CO - 4-CN-Ph

-N-Me,CH ₂ CH ₂ CH ₂ Cl CO Cl CO - p-biphenyl azetidino CO Cl CO NH 3,5-Cl-Ph azetidino CO Cl CO NH 3,5-F-Ph azetidino CO Cl CO - 2-naphthyl

CO azetidino CO Cl CO - 4-CN-Ph o azetidino CO Cl CO - p-biphenyl

3,5-Me-morpholine CO Cl CO NH 3,5-Cl-Ph

3,5-Me-morpholine cs Cl CO NH 3.5-Cl-Ph

3,5-Me-morpholine CO Cl CO NH 3,5-F-Ph

3,5-Me-morpholine cs Cl CO NH 3,5-F-Ph

3,5-Me-morpholine CO Cl CO - 2-naphthyl

3,5-Me-morpholine CO Cl CO - p-biphenyl

3,5-Me-morpholine CO Cl CO - 4-CN-Ph

3,5-Me-morpholine CS Cl CO - 2-naphthyl

3,5-Me-morpholine cs Cl CO - 4-CN-Ph

3,5-Me-morpholine cs Cl CO - p-biphenyl

fi Δ ^J m.p. r° c .

piperidino CS Cl CO NH 3,5-Cl-Ph piperidino CS Cl CO NH 3,5-F-Ph pyrrolidino CS Cl CO NH 3,5-Cl-Ph pyrrolidino CS Cl CO NH 3,5-F-Ph pyrrolidino CS Cl CO - 2-naphthyl pyrrolidino CS Cl CO - 4-CN-Ph pyrrolidino CS Cl CO - p-biphenyl

(CH ₃ ) ₂ -N CS Cl CO NH 3,5-F-Ph

(CH ₃ ) ₂ -N CS Cl CO - 4-CN-Ph

(CH ₃ ) ₂ -N CS Cl CO - p-biphenyl

(CH ₃ ) ₂ -N CS Cl CO - 2-naphthyl azetidino CS Cl CO NH 3,5-Cl-Ph azetidino CS Cl CO NH 3,5-F-Ph homopiperidine CS Cl CO NH 3,5-F-Ph homopiperidine CS Cl CO NH 3,5-Cl-Ph homopiperidine CS Cl CO - 2-naphthyl piperidino CS Cl CO - 2-naphthyl 132-135 piperidino cs Cl CO - p-biphenyl

X ^J B

CH _. CO Cl CO NH 3,5-F-Ph

-C(CH ₃ ) ₃ CO Cl CO NH 3,5-F-Ph

00 J

Ό^ CO Cl CO NH 3,5-F-Ph

CH ₃ CO Cl CO 2-naphthyl

—CH CH CO Cl CO 2-naphthyl

-C(CH ₃ ) ₃ CO Cl CO 2-naphthyl

NH

a o u o

CJ o J o υ o

CJ o CJ

H

XI o υ o J o υ o CJ o CJ o CJ

X ^J B H Δ ^J

-CH ₃ CO Cl CO NH 3,5-Cl-Ph

-CH ₂ -C1 CO Cl CO NH 3,5-Cl-Ph

-CF ₃ CO Cl CO NH 3,5-Cl-Ph

—CH CHo CO Cl CO NH 3,5-Cl-Ph

-CH ₂ -CF ₃ CO Cl CO NH 3,5-Cl-Ph

*-CH H CH CO Cl CO NH 3,5-Cl-Ph

—CH CH CH H CO Cl CO NH 3,5-Cl-Ph

-(CH ₂ ) ₄ CH ₃ CO Cl CO NH 3,5-Cl-Ph

-(CH ₂ ) ₅ CH ₃ CO Cl CO NH 3,5-Cl-Ph

00

-(CH ₂ ) ₆ CH ₃ CO Cl CO NH 3,5-Cl-Ph lb

—(CH- _/" JCHQ CO Cl CO NH 3,5-Cl-Ph

_. .CH,

: CO Cl CO NH 3 , 5-Cl-Ph

:H,

B H Δ ^J

-CH ₃ CS Cl CO NH 2-naphthyl -CF-, CS Cl CO NH 2-naphthyl

B H Δ ^J

O- CS Cl CO NH 2-naphthyl

Cl CS Cl CO NH 2-naphthyl

-CH ₃ CS Cl CO 3,5-Cl-Ph oo -CF CS Cl CO 3,5-Cl-Ph

O- CS Cl CO - 3,5-Cl-Ph

CH ₃ CS Cl CO - 4-CN-Ph

o- CS Cl CO - 4-CN-Ph

x ^J B H Δ ^J

CH, CS Cl CO p-biphenyl

0- CS Cl CO p-biphenyl

- -CN Cl CO NH 3,5-F-Ph

- -CN Cl CO NH 3,5-Cl-Ph

- -CN Cl CO - p-biphenyl oo

-CH ₃ so ₂ Cl CO NH 3,5-Cl-Ph 00

-CF ₃ so ₂ Cl CO - 2-naphthyl

-CH ₂ C=C-CF ₃ so ₂ Cl CO NH 3,5-F-Ph

—(CHp)2 **_ so ₂ Cl CO - p-biphenyl

—(CH / H so ₂ Cl CO - 2-naphthyl

-(CH ₂ ) ₂ CH ₃ so ₂ Cl CO - 4-CN-Ph

—(CH )2 H so ₂ Cl CO NH 3,5-F-Ph

—(CH / CH so ₂ Cl CO NH 3,5-Cl-Ph

2,4-Cl-Ph so ₂ Cl CO - 2-naphthyl

(Me) ₂ -N so ₂ Cl CO NH 3,5-Cl-Ph

rH rt rrt rt rt rt trt fa rrt bl bl A bl i bl bl bl X! bl s 1 bl xi

Xi xs XS fa Xi XS fa XS X! fl XS fa xs X! fa m x; fa x» fa χι 1 fa x> fa Φ 1 CU 1 X XS 1

XS XS rt 1 XS rt 1 S A Xi rt xs 1 rH fa xs rt

Cl- fa CU U fa CU CJ fa cu U 04 CJ

•rt id | cu fa CJ d 1 id 1 u υ lO 1 id I 1 id 1 1 id rrt id α tn fl in in tn

_^ fl in fl

_* A β i 8 in in in CJ fl in

1 1 1 _^ 1 1 1 _^ v x fM cn ro ro en en fM CU Cl ro cn tn ro

X υ g X X X X

NH ' g Z 1 z g ' 1 g X

1 Z Z 1 1 Z

a o o o O O O O O O o O o o O O O O o o J U CJ CJ CJ CJ u CJ CJ CJ CJ CJ CJ u CJ CJ CJ CJ CJ rt trt rrt rrt rt rt rt rt rH rrt rt rt trt rt irt rt rt rt rt

M CJ U CJ CJ J υ u CJ CJ CJ CJ CJ J CJ CJ J CJ u CJ d

001 o d O O o O O d O o o O

CO CO CO O CO CO O CO CO O CO CO O O O CO CO

X ^J B

-CH ₂ Ph so Cl CO NH 3,5-F-Ph

-CH ₂ Ph so Cl CO - . 2-naphthyl

2,4-Cl-Ph- CH ₂ - so Cl CO NH 3,5-Cl-Ph

2,4-Cl-Ph- CH ₂ - so Cl CO NH 2-naphthyl

4-CF ₃ -Ph so Cl CO NH 3,5-Cl-Ph

CH ₃ CO Cl CO NH 3,5-Cl-Ph

CH ₃ CO Cl CO NH 3,5-F-Ph

CH ₃ CO Cl CO - 2-naphthyl

CH ₃ CO Cl CO - 4-CN-Ph 10 o

CH ₃ CO Cl CO - p-biphenyl

—CH CH CH ■ -Cl CO Cl CO NH 3,5-Cl-Ph

—Ci- CH H • -Cl CO Cl CO - 2-naphthyl

-(CH2)^CH- _j so Cl CO NH 3,5-Cl-Ph

-(CH ₂ ) ₄ CH ₃ so Cl CO - 2-naphthyl

-(CH ₂ ) ₅ CH ₃ so Cl CO NH 3,5-Cl-Ph

-(CH ₂ ) ₅ CH ₃ so Cl CO - 2-naphthyl

-(CH ₂ ) ₆ CH ₃ so Cl CO NH 3,5-F-Ph

-(CH ₂ )gCH ₃ so Cl CO - 4-CN-Ph

—(CH )-yCH so Cl CO NH 3,5-Cl-Ph

—(CH )TCH so Cl CO - 2-naphthyl

-(CH ₂ ) ₈ CH ₃ so Cl CO NH 3,5-F-Ph

X ¹ B X H z Δ ¹

-<CH ₂ ) ₈ ^ι CH ₃ SO Cl CO NH 3,5-Cl-Ph

-(CH ₂ ) ₈ ι CH ₃ SO Cl CO - 2-naphthyl

-CH ₂ CF ₃ CO Cl CO NH 3,5-Cl-Ph

—CH^CF CO Cl CO NH 3,5-F-Ph

-CH ₂ CF ₃ CO Cl CO - 2-naphthyl

-CH ₂ CF ₃ CO Cl CO - 4-CN-Ph

—CH CFo CO Cl CO - p-biphenyl

-CH ₂ Ph CO Cl CO NH 3,5-Cl-Ph

-CH ₂ Ph CO Cl CO NH 3,5-F-Ph vo

-CH ₂ Ph CO Cl CO - 4-CN-Ph

-CH ₂ Ph CO Cl CO - 2-naphthyl

-CH ₂ Ph CO Cl CO - p-biphenyl

4-Cl-Ph- CH ₂ - CO Cl CO NH 3,5-Cl-Ph

4-Cl-Ph- CH ₂ - CO Cl CO NH 3,5-F-Ph

4-Cl-Ph- CH ₂ - CO Cl CO - 4-Cl-Ph

4-Cl-Ph- CH ₂ - CO Cl CO - 4-CN-Ph

4-Cl-Ph- CH ₂ - CO Cl CO - p-biphenyl

4-CF ₃ -Ph -CH ₂ - CO Cl CO NH 3,5-Cl-Ph

4-CF ₃ -Ph -CH ₂ - CO Cl CO - 2-naphthyl

4-CF ₃ -Ph -CH ₂ - CO Cl CO - p-biphenyl

Formula o

The compounds of this invention will generally be used in formulation with a liquid or solid diluent or with an organic solvent. Useful formulations of the compounds of Formula I can be prepared in conventional ways. They include dusts, granules, pellets, solutions, emulsions, wettable powders, eraulsifiable concentrates and the like. Many of these may be applied directly. Sprayable formulations can be extended in suitable media and used at spray volumes of from about one to several hundred liters per hectare. High strength compositions are primarily used as intermediates for further formulation. The formulations, broadly, contain about 1% to 99% by weight of active ingredient(s) and at least one of a) about 0.1% to 35% surfactant(s) and b) about 5% to 99% solid or liquid inert diluent(s) . More specifically, they will contain these ingredients in the following approximate proportions:

Percent by Weight

Active Ingredient Diluent(s) surfactantfs)

Wettable Powders 20-90 0-74 1-10 and Water Disper- sible Granules

Oil Suspensions, 5-50 40-95 0-35 Emulsions, Solutions, (including Emulsifiable Concentrates)

Aqueous Suspensions 10-50 40-84 1-20

Dusts 1-25 70-99 0-5

Granules and Pellets 1-95 5-99 0-15

High Strength 90-99 0-10 0-2

Compositions

Lower or higher levels of active ingredient can, of course, be present depending on the intended use and the physical properties of the compound. Higher ratios of surfactant to active ingredient are sometimes desirable, and are achieved by incorporation into the formulation or by tank mixing.

Typical solid diluents are described in Watkins, e_t al. , "Handbook of Insecticide Dust Diluents and Carriers", 2nd Ed., Dorland Books, Caldwell, New Jersey. The more absorptive diluents are preferred for the wettable powders and the denser ones for dusts. Typical liquid diluents and solvents are described in Marsden, "Solvents Guide," 2nd Ed.,

Interscience, New York, 1950. Solubility under 0.1% is preferred for suspension concentrates; solution concentrates are preferably stable against phase separation at 0°C. "McCutcheon's Detergents and Emulsifiers Annual", MC Publishing Corp., Ridgewood, New Jersey, as well as Sisely and Wood, "Encyclopedia of Surface Active Agents", Chemical Publ. Co., Inc., New York, 1964, list surfactants and recommended uses. All formulations can contain minor amounts of additives to reduce foam, caking, corrosion, microbio¬ logical growth, etc. Preferably, ingredients should be approved by the U.S. Environmental Protection Agency for the use intended.

The methods of making such compositions are well known. Solutions are prepared by simply mixing the ingredients. Fine solid compositions are made by blending and, usually, grinding as in a hammer or fluid energy mill. Water dispersible granules may be produced by agglomerating a fine powder composition (see, for example, B. Cross and H. Scher, "Pesticide Formulations", ACS Symposium Series 371, American

Chemical Society, Washington, D. C, 1988, pp. 251---259). Suspensions are prepared by wet milling 5 (see, for example, Littler, U.S. Patent 3,060,084). Granules and pellets may be made by spraying the active material upon preformed granular carriers or by agglomeration techniques. See J. E. Browning, "Agglomeration", Chemical Engineering. Dec. 4, 1967, 10 pp. 147£f. and "Perry's Chemical Engineer's Handbook", 4th Edn., McGraw-Hill, N.Y., 1963, pp. &-59ff.

For further information regarding the art of formulation, see for example:

H. M. Loux, U.S. Patent 3,235,361, Feb. 15, 15 1966, Col. 6, Line 16 through Col. 7, Line 19 and Examples 10 through 41.

R, W. Luckenbaugh, U.S. Patent 3,309,192, r. March 14, 1967, Col. 5, Line 43 through Col. 7, Line

62 pd Examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 20 138-140, 162-164, 166, 167, 169-182.

H. Gysin and E. Knusli, U.S. Patent 2,891,855, June 23, 1959, Col. 3, Line 66 through Col. 5, Line 17 and Examples 1-4.

G. C. Klingman, "Weed Control as a Science", 25 . John Wiley and Sons, Inc., New York, 1961, pp. 81-96. J. D. Fryer and S. A. Evans, "Weed Control Hand¬ book", 5th Edn. Blackwell Scientific Publications, Oxford, 1968, pp. 101-103.

30 Examples of useful formulations of compounds of the present invention are as follows:

35

EXAMPLE 371

Wettable Powder

N-[[[3,5-(dichlorophenyl)amino]carbonyl]oxy]- 2-(dimethylamino)-2-oxoethanimidoyl chloride

80%

Sodium Alkylnapthalenesulfonate 4% Sodium Ligninsulfonate 2%

Synthetic Amorphous Silica 1% Kaolinite 13%

The ingredients are blended, hammermilled, re-blended and packaged.

EXAMPLE 372

High Strength Concentrate N-[[[3,5-(dichlorophenyl)amino]carbonyl]oxy]-

2-( imethylamino)-2-oxoethanimidoyl chloride

98.5% Silica Aerogel 0.5%

Synthetic Amorphous Silica 1.0%

The ingredients are blended and ground in a ham ermill to produce a high strength concentrate essentially all passing a U.S.S. No. 50 Sieve (0.3 mm openings). This material may then be formulated in a variety of ways.

EXAMPLE 373

Solution

N-[[[3,5-(dichloropheny1)amino]carbony1]oxy]- 2-(dimethylamino)-2-oxoethanimidoyl chloride

30% N-methyl-2-pyrrolidone 70% The ingredients are combined and stirred to produce a solution, which can be used for low volume applications.

Utility

The compounds of this invention are useful as plant disease control agents. They provide control of diseases caused by a broad spectrum of fungal plant pathogens in the Basidiomycete. Ascomycete and Oomvcete classes. They are effective in controlling a broad spectrum of plant diseases, particularly foliar pathogens of ornamental, vegetable, field, cereal and fruit crops. These pathogens include, Plasmopora viticola-. Phvtophthora infestans. Peronospora tabacina, Pseudoperonosoora cubensis. Pvthium aphanidermatum. Alte_.nai.ia brassicae. SeptOfia nodorum. Cercosporidium personatum. Cercospora arachidicola, pgeu OO FCQSPOrellg herpotrichoides. Cercospora beticola. Botrvtis cinerea. Monilinia fructicόSLa. pyrjcularia prysae, Podosphaera leucotricha. Vent ria inaeαualis. Puccinia recondita. Puccinia gramπiinis / Hero le a vastatrix . Puccinia strilformis. Puccinia arachidis. and other species closely related to these pathogens.

The compounds of this invention can be mixed with fungicides, bactericides, acaricides, neiώaticides, insecticides, or other biologically active compounds in order to achieve desired results with a minimum expenditure of time, effort and

material. Suitable agents of this type are well-known to those skilled in the art. Some are listed below: Fungicides methyl 2-benzimidazolecarbamate (carbendazim) tetramethylthiuram disulfide (thiuram) n-dodecylguanidine acetate (dodine) manganese ethylenebisdithiocarbamate (maneb) l,4-dichloro-2,5-dimethoxybenzene (chloroneb)methyl l-(butylcarbamoyl)-2-benzimidazolecarbamate (benomyl) 2-cyano-N-ethylcarbamoyl-2-methoxyiminoace amide (cymoxanil) N-trichloromethylthiotetrahydrophthalamide (captan) N-trichloromethylthiophthalimide (folpet) dimethyl 4,4'-(o-phenylene)bis(3-thioallophanate)-

(thiophanate-methyl) 2-(thiazol-4-yl)benzimidazole (thiabendazole) aluminum tris(0-ethyl phosphonate)(phosethyl aluminum) tetrachloroisophthalonitrile (chlorothalonil)

2,6-dichloro-4-nitroaniline (dichloran) N-(2,6-dimethylphenyl)-N-(methoxyacetyl)alanine methyl ester (metalaxyl) cis-N-t1,1,2,2-tetrachloroethyl)thio]cyclohex-4-ene- 1,2-dicarbioximide (captafol)

3-(3,5-dichlorophenyl)-N-(l-methylethyl)-2,4-dioxo-l- imidazolidine carboxamide (iprodione) 3-(3,5-dichlorophenyl)-5-ethenyl-5-methyl-2,4-oxazoli- dinedione (vinclozolin) kasugamycin

0-ethyl-S,S-diphenylphosphorodithioate(edifenphos) 4-(3-(4-(l,l-dimethyl-ethyl)phenyl)-2-methyl)propyl- 2,6-dimethylmorpholine (Fenpropimorph)

4-(3-4(l,l-dimethyl-ethyl)phenyl)-2-methyl)propylpi- peridine (Fenpropidine)

Bayleton® l-(4-chlorophenoxy)-3,3-dimethyl-l- 1H-1,2,4-triazol-l-yl)butanone Systhane® 2-(4-chlorophenyl)-2-(lH-l,2,4- triazol-l-ylmethyl)hexanenitrile Folicur® (tebuconazol)

Score® 3-chloro-4-[4-methyl-2-(lH-l,2,4- triazol)-l-ylmethyl)-l,3-diσxolan- 2-yl]phenyl-4-chlorophenyl ether

Topaz® l-[2-(2,4-dichlorophenyl)pentyl]lH-l,2,4- triazole Impact® (±α-(2-fluorophenyl-«-(4-fluorophenyl)- 1H-1,2,4-triazole-1-ethano Nustar® l-[[bis(4-fluorophenyl)methylsilyl) methyl]-1H-1,2,4-triazole Sportak® l-N-propyl-N-[2(2,4,6-trichlorophenoxy) ethyl]carbamoylimidazole Tilt® 1-[[2-(2,4-dichlorophenyl)-4-propyl-l,3- dioxolan-2-yl]methyl]-lH-l,2,4-triazole

Rubigan® α-(2-chloroρhenyl)-α-(4-chlorophenyl)-5- pyridine-methanol copper oxychloride furalaxyl methyl N-(2,6-dimethylphenyl)-N- (2-furanylcarbonyl)-DL-alaninate

Bactericides tribasic copper sulfate streptomycin sulfate oxytetracycline

Acaricides senecioic acid, ester with 2-sec-butyl-4,6-dinitro- phenol (binapacryl) 6-methyl-l,3-dithiolo[2,3-B]quinonolin-2-one (oxythio- quinox)

2,2,2-trichloro-l,l-bis(4-chlorophenyl)ethanol- (dicofol) bis(pentachloro-2,4-cyclopentadien-l-yl) (dienochlor) tricyclohexyltin hydroxide (cyhexatin) hexakis(2-methyl-2-phenylpropyl)distannoxane (fenbutin oxide)

Nematicides

2-[diethoxyphosphinylimino]-l,3-diethietane

(fosthietan) S-methyl-1-( imethylcarbamoyl)-N-(methylcarbamoyloxy)- thioformimidate(oxamyl) S-methyl-1-carbamoyl-N-(methylcarbamoyloxy)thio- formimidate N-isopropylphosphoramidic acid, 0-ethyl-0'-[4-(methyl- thio)-m-tolyl]diester (fenamiphos)

Insecticides

3-hydroxy-N-methylcrotonamide(dimethylphosphate)ester

(monocrotophos) methylcarbamic acid, ester with 2,3-dihydro-2,2- dimethyl-7-benzofuranol (carbofuran) 0-[2,4,5-trichloro-a-(chloromethyl)benzyl]phosphoric acid, O' ,0'-dimethyl ester (tetrachlorvinphos) 2-mercaptosuccinic acid, diethyl ester, S-ester with thionophosphoric acid, dimethyl ester (malathion) phosphorothioic acid, 0,0-dimethyl, O-p-nitrophenyl ester (methyl parathion) methylcarbamic acid, ester with a-naphthol

(carbaryl) methyl N-[[(methylamino)carbonyl]oxy]ethanimidothio- ate (methomyl) N'-(4-chloro-o-tolyl)-N,N-dimethylformamidine (chlordimeform)

O,O-diethyl-0-(2-isoρropyl-4-methyl-6-pyrimidyl)- phosphorothioate (diazinon) octachlorocamphene (toxaphene)

O-ethyl O-p-nitrophenyl phenylphosphonothioate (EPN) cyano(3-phenoxyphenyl)-methyl 4-chloro-a-(l-methyl- ethyl)benzeneacetate (fenvalerate) (3-phenoxyphenyl)methyl (+)-cis,trans-3-(2,2-dichloro- ethenyl)-2,2-dimethylcyclopropanecarboxylate

(perraethrin) dimethyl N,N'-[thiobis(N-methylimmo)carbonyloxy]]- bis[ethanimidothioate] (thiodicarb) phosphorothiolothionic acid, 0-ethyl-0-[4-(methyl- tbio)phenyl]-S-n-propyl ester (sulprofos) a-cyano-3-phenoxybenzyl 3-(2,2-dichlorovinyl)-2,2- dimethylcyclopropane carboxylate (cypermethrin) cyano(3-phenoxyphenyl)methyl 4-(difluoromethoxy)- a-(methylethyl)benzeneacetate (flucythrinate) 0,0-diethyl-0-(3,5,6-trichloro-2-pyridyl)phosphoro- thioate (chlorpyrifos) O,0-dimethyl-S-[(4-oxo-l,2,3-benzotriazin-3-(4H)-yl)- methyl]phosphorodithioate (azinphos-methyl) 5,6-dimethyl-2-dimethylamino-4-pyrimidinyl dimethyl carbamate (pirimicarb)

S-(N- ormyl-N-methylcarbamoylmethyl)-O,0-dimethy1 phosphorodithioate (formothion) S-2-(ethylthioethyl)-0,0-dimethyl phosphiorothioate

(demeton-S-methyl) a-cyano-3-phenoxybenzyl cis-3-(2,2-dibromovinyl)-

2,2-dimethylcyclopropane carboxylate (deltamethrin) cyano(3-phenoxyphenyl)methyl ester of N-(2-chloro-4- trifluoromethylphenyl)alanine (fluvalinate)

Application

Disease control is ordinarily accomplished by applying an effective amount of the compound, pre-infection, to the portion of the plant to be protected such as the roots, stems, foliage, fruit, seeds, tubers or bulbs. The compound may also be applied to the seed, to protect the seed and seedling. Rates of application for these compounds can be influenced by many factors of the environment and should be determined under actual use conditions. Foliage can normally be protected when treated at a rate of from less than 10 g/ha to 10,000 g/ha of active ingredient. Seed and seedlings can normally be protected when seed is treated at a rate of from .1 to 10 g per kilogram of seed.

Examp -A

The test compounds were dissolved in acetone in an amount equal to 3% of the final volume and then suspended at a concentration of 200 ppm in purified water containing 250 ppm of the surfactant Trem 014 (polyhydric alcohol esters) . This suspension was sprayed to the point of run-off on apple seedlings. The following day the seedlings were inoculated with a spore suspension of Venturia inaequalis (the causal agent of apple scab) and incubated in a saturated atmosphere at 20°C for 24 hr, and then moved to a growth chamber at 22°C for 11 days, after which disease ratings were made.

Example g

The test compounds were dissolved in acetone in an amount equal to 3% of the final volume and then suspended at a concentration of 200 ppm in purified water containing 250 ppm of the surfactant Trem 014 (polyhydric alcohol esters) . This suspension was sprayed to the point of run-off on peanut seedlings.

The following day the seedlings were inoculated with a spore suspension of Cercosporidium persoriatum (the causal agent of peanut late leafspot) and incubated in a s.aturated atmosphere at 22°C for 24 hr, a high humidity atmosphere at 22 to 30°C for 5 days, and then moved to a growth chamber at 29°C for 6 days, after which disease ratings were made.

Example C

The test compounds were dissolved in acetone in an amount equal to 3% of the final volume and then suspended at a concentration of 200 ppm in purified water containing 250 ppm of the surfactant Trem 014 (polyhydric alcohol esters). This suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore suspension of Puccinia recondita (the causal agent of wheat leaf rust) and incubated in a saturated atmosphere at 20°C for 24 hr, and then moved to a growth chamber at 20°C for 6 days, after which disease ratings were made.

Example D

The test compounds were dissolved in acetone in an amount equal to 3% of the final volume and then suspended at a concentration of 200 ppm in purified water containing 250 ppm of the surfactant Trem 014 (polyhydric alcohol esters). This suspension was sprayed to the point of run-off on rice seedlings.

The following day the seedlings were inoculated with a spore suspension of Pyricularia oryzae (the causal agent of rice blast) and incubated in a saturated atmosphere at 27°C for 24 hr, and then moved to a growth chamber at 30°C for 5 days, after which disease ratings were made.

Example E

The test compounds were dissolved in acetone in an amount equal to 3% of the final volume and then suspended at a concentration of 200 ppm in purified water containing 250 ppm of the surfactant Trem 014 (polyhydric alcohol esters). This suspension was sprayed to the point of run-off on tomato seedlings. The following day the seedlings were inoculated with a spore suspension of Phvtophthora infestans (the causal agent of potato and tomato late blight) and incubated in a saturated atmosphere at 20°C for 24 hr, and then moved to a growth chamber at 20°C for 5 days, after which disease ratings were made.

Example F

The test compounds were dissolved in acetone in an amount equal to 3% of the final volume and then suspended at a concentration of 200 ppm in purified water containing 250 ppm of the surfactant Trem 014 (polyhydric alcohol esters). This suspension was sprayed to the point of run-off on grape seedlings.

The ^" following day the seedlings were inoculated with a spore ^' suspension of Plasmopara viticola (the causal agent of gra^e downy mildew) and incubated in a saturated atmosphere at 20°C for 24 hr, moved to a growth chamber at 20°C for 6 days,and then incubated in a saturated atmosphere at 20°C for 24 hr, after which disease ratings were made.

Example G

The test compounds were dissolved in acetone in an amount equal to 3% of the final volume and then suspended at a concentration of 200 ppm in purified water containing 250 ppm of the surfactant Trem 014 (polyhydric alcohol esters). This suspension was sprayed to the point of run-off on cucumber seedlings. The following day the seedlings were inoculated with a spore suspension of Botrvtis cinerea (the causal agent of gray mold on many crops) and incubated in a saturated atmosphere at 20°C for 48 hr, and moved to a growth chamber at 20°C for 5 days, after which disease ratings were made.

Example fl

The test compounds were dissolved in acetone in an amount equal to 3% of the final volume and then suspended at a concentration of 200 ppm in purified water containing 250 ppm of the surfactant Trem 014 (polyhydric alcohol esters) . This suspension was sprayed to the point of run-off on sugar beet seedlings. The following day the seedlings were inoculated with a spore suspension of Cercospora beticola (the causal agent of sugar beet leafspot) and incubated in a a high humidity atmosphere at 22 to 30°C for 3 days, and then moved to a greenhouse at 20 to 25°C for 7 days, after which disease ratings were made.

Example I

The test compounds were dissolved in acetone in an amount equal to 3% of the final volume and then suspended at a concentration of 1000 ppm in purified water containing 250 ppm of the surfactant Trem 014 (polyhydric alcohol esters). This suspension was sprayed to the point of run-off on tobacco seedlings. The following day the seedlings were inoculated with a spore suspension of Peronospora tabacina (the causal agent of tobacco blue mold) and incubated in a saturated atmosphere at 20°C for 24 hr, moved to a growth chamber at 22°C for 6 days,and then incubated in a saturated atmosphere at 20°C for 24 hr, after which disease ratings were made.

Example J

The test compounds were dissolved in acetone in an amount equal to 3% of the final volume and then suspended at a concentration of 200 ppm in purified water containing 250 ppm of the surfactant Trem 014 (polyhydric alcohol esters) . This suspension was sprayed to the point of run-off on cucumber seedlings. The following day the seedlings were inoculated with a spore suspension of Pseudoperonospora cubensis (the causal agent of cucumber downy mildew) and incubated in a saturated atmosphere at 20°C for 24 hr, moved to a growth chamber at 20°C for 6 days, and then incubated in a saturated atmosphere at 20°C for 24 hr, after which disease ratings were made.

Results for Examples A to J are given in Table A, B, and/or C. Data in Tables A and C are the average of three replicates. Data in Table B are from a single replicate. In the tables, a rating of 100 indicates 100% disease control and a rating of 0 indicates no disease control relative to the carrier sprayed controls) . NT indicates that no test was performed.

TABLE A

CMPD EX EX EX EX EX EX EX

NO. A B C D E F G

1 100 88 97 93 100 100 99

2 100 NT 97 NT 100 100 NT

3 100 88 90 93 100 100 99

4 100 92 96 94 100 100 99

5 100 49 50 80 100 100 NT

6 100 95 97 97 100 100 NT

7 100 100 82 85 100 100 99

8 100 100 100 95 100 100 99

9 100 75 85 93 100 100 14

10 100 98 97 91 100 100 99

11 100 100 97 97 100 100 99

12 100 98 97 89 100 100 90

13 100 90 99 73 100 100 99

14 100 82 27 26 100 91 5

15 100 98 97 94 100 100 97

16 100 95 99 95 100 100 67

17 100 40 84 0 73 100 3

28 100 98 97 79 100 100 99

19 100 92 96 40 100 100 66

20 100 97 100 93 100 100 99

21 95 96 100 97 100 100 99

22 95 NT 8 NT NT 100 NT

26 29 NT 0 NT NT 55 NT

27 100 99 84 92 100 100 99

28 0 NT NT NT NT NT NT

30 96 NT 26 NT 81 100 NT

31 100 NT NT NT NT NT NT

CMPD EX EX EX EX EX EX EX

NO. A B C D E F G

32 100 100 97 94 100 100 99

33 100 89 100 94 100 100 99

34 100 62 37 0 99 100 94

35 34 36 96 0 91 99 0

36 100 69 91 71 100 100 99

37 100 75 90 27 100 100 99

38 100 14 69 21 96 100 3

39 100 97 99 84 99 100 0

40 96 29 43 21 95 99 0

41 99 14 0 14 9 100 2

42 100 99; 94 93 100 100 99

43 ιop NT 0 NT 84 100 NT

44 99 10 43 0 0 86 34

45 99 0 0 13 43 96 1

46 100 91 86 91 100 100 90

47 100 21 56 71 92 100 3

48 100 69 77 96 100 100 1

49 99 58 52 34 97 98 0

50 100 89 91 74 99 100 3

51 100 96 43 41 100 100 4

52 100 94 100 60 100 100 NT

53 100 NT 26 NT NT 100 NT

54 100 NT 95 77 100 100 NT

55 100 77 99 89 100 100 94

56 ^* 100 96 47 84 100 100 NT

57 100 96 69 67 100 100 NT

58 6 NT NT 10 7 39 NT

59 1043 NT 87 38 99 98 99

60 99 NT 88 41 96 100 94

61 100 91 88 97 98 100 0

CMPD EX EX EX EX EX EX EX

NO . A B C D E F G

62 100 87 88 97 91 100 29

63 100 79 17 76 98 100 15

64 100 26 17 13 85 74 15

65 100 9 0 13 0 2 0

66 100 13 0 28 84 65 1

67 100 99 85 NT 100 100 59

68 100 98 25 60 95 100 1

69 100 96 94 52 52 100 0

70 100 NT 80 60 99 100 4

71 100 NT 90 60 97 100 17

72 100 NT 97 53 99 100 31

73 100 NT 97 62 99 100 94

74 100 NT 92 86 97 100 1

75 100 NT 93 83 99 100 31

76 100 NT 94 88 99 98 49

77 100 NT 75 10 98 100 4

78 100 88 87 57 100 100 74

79 100 85 100 97 100 100 49

80 100 98 99 71 100 100 97

81 96 93 63 71 100 100 90

82 100 93 91 66 100 100 97

83 100 9 53 14 61 100 18

84 100 100 58 NT 100 99 NT

85 100 81 26 74 100 100 45

86 100 83 62 85 100 100 85

87 100 97 70 62 100 100 85

88 100 63 87 85 100 100 77

89 100 77 90 82 100 100 NT

90 100 97 70 85 100 100 32

91 100 31 66 NT 98 100 NT

92 100 NT 53 85 100 100 83

CMPD EX EX EX EX EX EX EX

NO. A B C D E F G

93 100 NT 0 NT 9 52 NT

94 100 NT 0 NT 31 42 NT

95 100 62 18 NT 99 95 0

96 100 NT 0 NT 9 70 NT

97 100 96 99 89 100 100 99

98 100 26 93 14 95 100 4

99 96 55 96 14 95 100 4

100 96 26 100 14 99 100 30

101 0 26 0 7 0 39 15

102 81 13 63 0 87 100 1

103 99 13 91 14 89 100 4

104 100 0 70 0 87 99 0

106 100 93 63 91 100 100 18

107 100 35 87 32 100 100 3

108 100 94 100 96 100 100 99

109 96 64 18 16 100 100 1

110 100 94 84 94 100 100 99

111 81 50 0 16 17 100 3

112 100 88 91 96 100 100 4

113 100 88 100 38 100 100 31

114 36 3 0 11 0 15 4

115 100 NT NT NT NT NT NT

116 100 NT NT NT 46 37 NT

117 100 NT NT NT 9 22 NT

118 100 NT NT NT 0 100 NT

119 100 NT 16 NT 72 100 NT

120 100 85 89 NT 98 100 99

121 100 76 0 0 98 100 0

122 93 70 34 48 99 100 40

12a 20 65 0 12 7 30 0

CMPD EX EX EX EX EX EX EX

NO. A B C D E F G

124 100 70 46 0 0 100 0

125 87 41 10 0 0 8 62

126 100 86 97 93 100 100 NT

127 100 NT 93 73 100 100 NT

128 100 58 62 NT 100 100 NT

129 100 72 98 95 100 100 4

130 100 42 91 54 100 100 NT

131 96 0 0 0 96 94 1

132 100 18 0 0 82 100 1

133 100 35 36 26 100 100 29

134 16 0 0 0 0 59 1

135 100 0 0 0 73 97 16

136 81 55 84 NT 97 100 21

137 100 61 82 NT 100 100 94

138 100 71 84 NT 99 100 99

139 100 NT 24 NT 55 98 NT

140 81 NT 79 NT 99 100 90

141 100 88 77 NT 98 98 95

142 100 74 87 NT 99 100 NT

143 99 90 82 NT 100 100 94

144 100 83 100 9 100 100 48

145 100 73 97 39 100 100 17

146 100 NT NT NT 29 86 NT

147 100 NT NT NT NT NT NT

148 100 NT NT NT 96 100 NT

149 100 NT NT NT 85 86 NT

150 100 74 100 NT 100 100 45

151 100 82 49 0 94 91 3

152 100 71 75 0 100 100 31

153 100 34 96 17 100 100 34

154 100 0 0 0 39 100 3

CMPD EX EX EX EX EX EX EX

NO. A B C D E F G

155 100 0 0 0 0 30 4

156 100 0 0 0 8 99 3

157 10,0 12 0 0 0 70 3

158 87 0 0 0 0 66 3

159 53 0 0 0 0 91 1

160 41 0 0 0 0 14 0

161 87 0 0 0 0 62 3

162 100 27 96 90 98 100 4

163 100 0 87 27 94 100 0

164 100 84 87 90 99 100 1

165 100 96 89 87 100 100 NT

166 100 78 100 84 100 100 NT

167 100 0 93 85 68 100 1

168 100 NT 80 9 96 100 NT

169 100 0 32 0 24 90 0

170 92 64 85 85 100 100 0

171 82 0 16 0 0 4 0

172 100 NT NT NT NT NT NT

175 34 NT 18 4 NT NT NT

176 100 NT NT NT NT NT NT

177 100 NT NT NT NT NT NT

178 100 36 NT NT 100 100 NT

179 100 NT 78 0 99 100 NT

180 lQO 82 86 8 99 100 18

181- 100 25 18 NT 99 100 20

182 NT NT NT NT NT NT NT

183 100 66 89 NT 100 100 NT

184 100 66 70 51 100 100 NT

185 100 93 90 8 100 100 7

186 184 39 0 NT 84 100 NT

CMPD EX EX EX EX EX EX EX

NO. A B C D E F G

188 91 NT 36 0 92 100 NT

190 100 NT 36 NT 100 100 NT

191 NT 97 96 6 98 100 NT

192 100 99 93 8 100 100 6

193 100 95 97 15 100 100 93

194 100 9 94 8 100 100 6

195 NT NT NT NT 27 0 NT

197 63 NT NT NT NT NT NT

198 72 NT NT NT NT NT NT

199 100 17 22 NT 99 97 NT

200 25 NT NT NT NT NT NT

203 8 NT 24 0 8 42 NT

204 16 NT NT NT NT NT NT

205 100 35 90 0 100 100 NT

207 100 38 14 NT 44 100 NT

208 NT NT NT 0 NT NT 0

209 99 NT 55 19 97 100 0

210 91 NT 45 10 98 100 27

211 66 NT 37 0 88 100 0

212 99 NT 0 NT 17 99 NT

213 NT 100 100 99 100 100 NT

214 93 42 69 0 36 96 NT

215 87 20 88 0 88 100 NT

216 100 70 99 67 100 100 NT

217 67 0 17 NT 98 97 NT

218 69 NT 17 NT 42 97 NT

219 100 NT 90 NT 99 100 NT

220 100 NT 93 NT 99 100 NT

221 100 61 100 85 100 100 4

222 100 97 97 26 100 100 NT

223 100 61 99 NT 100 100 99

CMPD EX EX EX EX EX EX EX

NO. A B C D E F G

224 100 98 97 26 100 100 4

225 93 NT 69 NT 94 100 NT

226 100 14 61 NT 100 100 NT

227 100 14 35 NT 100 100 NT

228 75 NT 88 NT 98 99 NT

229 100 56 88 NT 100 100 NT

230 67 0 17 NT 100 100 NT

231 0 NT 35 NT 84 85 NT

232 100 14 84 NT 100 100 NT

233 86 0 17 NT 98 100 NT

235 100 51 92 21 97 100 NT

237 99 60 67 NT 31 54 NT

238 NT NT NT NT 31 35 NT

239 NT 60 67 NT NT NT NT

240 NT 14 51 NT 97 NT NT

241 NT 14 75 NT NT NT 61

242 100 NT 35 NT 100 100 NT

243 100 NT 75 NT 100 100 NT

244 93 0 12 NT NT NT NT

245 9 NT NT 0 NT NT NT

TABM: B

CMPD EX EX EX EX EX

NO. A B D E G

23 33 0 0 0 6

29 47 14 0 0 0

105 69 0 0 0 7

173 69 24 0 0 0

174 42 0 0 0 0

187 0 0 0 0 0

189 4 0 25 0 0

196 NT 0 0 0 0

201 12 0 0 0 0

202 0 27 0 0 0

206 0 1 0 0 9

234 100 95 85 99 0

236 67 34 27 76 11

246 100 91 67 99 0

247 100 96 97 99 4

248 100 96 85 92 0

249 100 0 27 97 0

251 100 0 0 97 0

252 100 0 27 44 0

253 90 0 27 0 0

254 100 0 27 NT 0

255 90 34 0 22 0

256 100 96 97 99 90

257 100 82 97 99 11

258 100 64 0 92 0

259 100 64 86 99 94

260 96 0 0 63 0

261 100 91 99 99 99

262 100 0 0 25 0

CMPD EX EX EX EX EX

NO. A B D E G

263 100 81 99 99 89

264 100 64 99 99 89

288 100 29 0 99 0

289 96 29 0 96 0

291 96 62 0 96 8

292 100 96 0 99 82

293 96 62 27 61 8

296 0 29 0 19 8

297 0 29 0 42 0

298 100 62 0 92 0

299 100 62 0 75 0

300 100 91 85 99 98

301 100 62 67 99 69

302 99 29 0 61 8

303 90 62 0 85 0

304 68 0 0 19 8

TABLE C

CMPD EX EX EX

NO. H I J

1 100 100 100

2 63 100 94

3 88 98 96

4 26 70 10

5 32 96 64

6 95 96 100

7 100 96 100

8 94 96 100

9 51 100 61

10 94 98 100

11 75 96 100

12 27 100 32

42 100 80 100