Method for preparing fused oxazinones from ortho-amino aromatic carboxylic acid and carboxylic acid in the presence of a sulfonyl chloride and pyridine

1. A method for preparing a fused oxazinone of Formula 1,

wherein

K is, together with the two contiguous linking carbon atoms, a fused phenyl ring optionally substituted with from one to four substituents independently selected from G, U, W or R 13 ;

J is a pyrrole ring or a pyrazole ring, each optionally substituted with from one to four substituents independently selected from G, U, W or R 13 ;

each G is a 5- or 6-membered nonaromatic heterocyclie ring optionally with one or two ring members selected from the group consisting of C(═O), SO or S(O) 2 , each optionally substituted with from one to four substituents independently selected from W;

each U is a phenyl ring, a benzyl group, a benzoyl group, a 5- or 6-membered heteroaromatic ring, an aromatic 8-, 9- or 10-membered fused carbobicyclic ring system, an aromatic 8-, 9- or 10-membered fused heterobicyclic ring system, each optionally substituted with from one to four substituents independently selected from W;

each W is independently C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 3 -C 6 cycloalkyl, C 1 -C 4 haloalkyl, C 2 -C 4 haloalkenyl, C 2 -C 4 haloalkynyl, C 3 -C 6 halocycloalkyl, halogen, CN, NO 2 , C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, C 1 -C 4 alkylamino, C 2 -C 8 dialkylamino, C 3 -C 6 cycloalkylamino, (C 1 -C 4 alkyl)(C 3 -C 6 cycloalkyl)amino or C 3 -C 6 trialkylsilyl;

each R 12 is independently R 19 C(═E)- or —O(Q═)P(OR 19 ) 2 ;

each R 13 is B(OR 17 ) 2 ; NH 2 ; SH; thiocyanato; C 3 -C 8 trialkylsilyloxy; C 1 -C 4 alkyldisulfide; SF 5 ; R 19 C(═E)-; R 19 C(═E)M-; R 19 MC(═E)-; (R 19 )MC(═E)M-; —OP(═Q)(OR 19 ) 2 ; —S(O) 2 MR 19 ; or R 19 S(O) 2 M-;

each E independently O, S, NR 15 , NOR 15 , NN(R 15 ) 2 , N—S═O, N—CN or N—NO 2 ;

each M is independently O, NR 18 or S;

Q is O or S;

each R 15 and each R 19 is independently H; C 1 -C 6 alkyl optionally substituted with one, or more substituents selected from the group consisting of CN, NO 2 , hydroxy, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 1 -C 4 alkythio, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, C 1 -C 4 haloalkylthio, C 1 -C 4 haloalkylsulfinyl, C 1 -C 4 haloalkylsulfonyl, C 1 -C 4 alkylamino, C 2 -C 8 dialkylamino, CO 2 H, C 2 -C 6 alkoxycarbonyl, C 2 -C 6 alkylcarbonyl, C 3 -C 6 trialkylsilyl, and a phenyl ring optionally substituted with one to three substituents independently selected from W; C 1 -C 6 haloalkyl; C 3 -C 6 cycloalkyl; or a phenyl ring optionally substituted with from one to three substituents independently selected from W;

each R 17 is independently H or C 1 -C 4 alkyl; or

B(OR 17 ) 2 can form a ring wherein the two oxygen atoms are linked by a chain of two to three carbons optionally substituted with one or two substituents independently selected from methyl or C 2 -C 6 alkoxycarbonyl; and

each R 18 is independently H, C 1 -C 6 alkyl or C 1 -C 6 haloalkyl,

comprising:

(1) contacting a carboxylic acid of Formula 2

J—CO 2 H  2

with a sulfonyl chloride of Formula 4

LS(O) 2 Cl  4

wherein

L is selected from alkyl, haloalkyl, and phenyl optionally substituted with from one to three substituents independently selected from alkyl or halogen;

in the presence of a Formula 3 compound selected from the group consisting of pyridine, quinoline, isoquinoline and pyridine substituted with alkyl, dimethylamino, or pyrrolidino,

the nominal mole ratio of sulfonyl chloride to carboxylic acid being from about 0.75 to 1.5;

(2) contacting the mixture prepared in (1) with an ortho-amino aromatic carboxylic acid of Formula 5

in the presence of a Formula 3 compound selected from the group consisting of pyridine, quinoline, isoquinoline and pyridine substituted with alkyl, dimethylamino, or pyrrolidino, the nominal mole ratio of the ortho-amino aromatic carboxylic acid to carboxylic acid charged in (1) being from about 0.8 to 1.2; and

(3) adding additional sulfonyl chloride to the mixture prepared in (2), the nominal mole ratio of additional sulfonyl chloride added in (3) to carboxylic acid charged in (1) being at least about 0.5.

2. The method of claim 1 wherein in (1) the carboxylic acid of Formula 2 is contacted with sulfonyl chloride of Formula 4 in the presence of a Formula 3 compound selected from the group consisting of pyridine, 3-picoline, 2,6-lutidine, collidine, 2-picoline and 4-picoline and in (2) the mixture prepared in (1) is contacted with the ortho-amino aromatic carboxylic acid of Formula 5 in the presence of a Formula 3 compound selected from the group consisting of pyridine, 3-picoline, 2,6-lutidine, collidine, 2-picoline and 4-picoline.

3. The method of claim 1 wherein sulfonyl chloride of Formula 4 is selected from the group consisting of methanesulfonyl chloride, propanesulfonyl chloride and benzene sulfonyl chloride.

4. The method of claim 1 wherein the nominal mole ratio of sulfonyl chloride to carboxylic acid in (1) is from about 1.0 to 1.5; the nominal mole ratio of the ortho-amino aromatic carboxylic acid in (2) to carboxylic acid charged in (1) is from about 0.9 to 1.1; the nominal mole ratio of additional sulfonyl chloride added in (3) to carboxylic acid charged in (1) is from about 1.0 to 1.5.

5. The method of claim 4 wherein the nominal mole ratio of the Formula 3 compound charged in (1) to carboxylic acid charged in (1) is from about 1.0 to 2.0; additional Formula 3 compound is charged in (2); and the nominal mole ratio of the additional Formula 3 compound charged in (2) to carboxylic acid charged in (1) is from about 2.0 to 4.0.

6. The method of claim 1 wherein K is, together with the two contiguous linking carbon atoms, a fused phenyl ring optionally substituted with from one to four substituents independently selected from W or R 13 .

7. The method of claim 1 wherein a compound of Formula 1a

wherein

X is N or CR 6 ;

Y is N or CH;

R 4 is C 1 -C 4 alkyl or halogen;

R 5 is H, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl or halogen;

R 6 and R 7 are independently H, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, halogen, CN or C 1 -C 4 haloalkoxy,

R 8 is H, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 3 -C 6 cycloalkyl, C 1 -C 4 haloalkyl, C 2 -C 4 haloalkenyl, C 2 -C 4 haloalkynyl, C 3 -C 6 halocycloalkyl, halogen, CN, NO 2 , C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, C 1 -C 4 alkylamino, C 2 -C 8 dialkylamino, C 3 -C 6 cycloalkylamino, (C 1 -C 4 alkyl)(C 3 -C 6 cycloalkyl)amino, C 2 -C 4 alkylcarbonyl, C 2 -C 6 alkoxycarbonyl, C 2 -C 6 alkylaminocarbonyl, C 3 -C 8 dialkylaminocarbonyl or C 3 -C 6 trialkylsilyl; and

R 9 is CF 3 , OCF 3 , OCHF 2 , OCH 2 CF 3 or halogen;

is prepared using a compound of Formula 2′ as the Formula 2 compound and a compound of Formula 5′ as the Formula 5 compound

8. The method of claim 7 wherein

X is N;

Y is N;

R 4 is CH 3 , F, Cl or Br;

R 5 is CF 3 , F, Cl, Br or I;

R 7 is Cl or Br,

R 8 is H; and

R 9 is CF 3 , OCHF 2 , OCH 2 CF 3 , Cl or Br.

9. A method for preparing a fused oxazinone of Formula 1a

wherein

X is N or CR 6 ;

Y is N or CH;

R 4 is C 1 -C 4 alkyl or halogen;

R 5 is H, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl or halogen;

R 6 and R 7 are independently H, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, halogen, CN or C 1 -C 4 haloalkoxy;

R 8 is H, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 3 -C 6 cycloalkyl, C 1 -C 4 haloalkyl, C 2 -C 4 haloalkenyl, C 2 -C 4 haloalkynyl, C 3 -C 6 halocycloalkyl, halogen, CN, NO 2 , C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, C 1 -C 4 alkylamino, C 1 -C 4 dialkylamino, C 3 -C 6 cycloalkylamino, (C 1 -C 4 alkyl)(C 3 -C 6 cycloalkyl)amino, C 2 -C 4 alkylcarbonyl, C 2 -C 6 alkoxycarbonyl, C 2 -C 6 alkylaminocarbonyl, C 3 -C 8 dialkylaminocarbonyl or C 3 -C 6 trialkylsilyl;

R 9 is CF 3 , OCF 3 , OCHF 2 , OCH 2 CF 3 , S(O) p CHF 3 , S(O) p CHF 2 or halogen; and

p is 0, 1 or 2;

comprising:

(1) contacting a carboxylic acid of Formula 2′

with a sulfonyl chloride of Formula 4

LS(O) 2 Cl  4

wherein

L is selected from alkyl, haloalkyl, and phenyl optionally substituted with from one to three substituents independently selected from alkyl or halogen;

in the presence of a Formula 3 compound selected from the group consisting of pyridine, quinoline, isoquinoline and pyridine substituted with alkyl, dimethylamino, or pyrrolidino, the nominal mole ratio of sulfonyl chloride to carboxylic acid being from about 0.75 to 1.5;

(2) contacting the mixture prepared in (1) with an ortho-amino aromatic carboxylic acid of Formula 5′

in the presence of a Formula 3 compound selected from the group consisting of pyridine, quinoline, isoquinoline and pyridine substituted with alkyl, dimethylamino, or pyrrolidino, the nominal mole ratio of the ortho-amino aromatic carboxylic acid to carboxylic acid charged in (1) being from about 0.8 to 1.2; and

(3) adding additional sulfonyl chloride to the mixture prepared in (2), the nominal mole ratio of additional sulfonyl chloride added in (3) to carboxylic acid charged in (1) being at least about 0.5.

10. The method of claim 9 wherein in (1) the carboxylic acid of Formula 2 is contacted with sulfonyl chloride of Formula 4 in the presence of a Formula 3 compound is selected from the group consisting of pyyridine, 3-picoline, 2,6-lutidine, collidine, 2-picoline and 4-picoline and in (2) the mixture prepared in (1) is contacted with the ortho-amino aromatic carboxylic acid of Formula 5 in the presence of a Formula 3 compound selected from the group consisting of pyridine, 3-picoline, 2,6-lutidine, collidine, 2-picoline and 4-picoline.

11. The method of claim 9 wherein sulfonyl chloride of Formula 4 is selected from the group consisting of methanesulfonyl chloride, propanesulfonyl chloride and benzene sulfonyl chloride.

12. The method of claim 9 wherein the nominal mole ratio of sulfonyl chloride to carboxylic acid in (1) is from about 1.0 to 1.5; the nominal mole ratio of the an ortho-amino aromatic carboxylic acid in (2) to carboxylic acid charged in (1) is from about 0.9 to 1.1; the nominal mole ratio of additional sulfonyl chloride added in (3) to carboxylic acid charged in (1) is from about 1.0 to 1.5.

13. The method of claim 12 wherein the nominal mole ratio of the Formula 3 compound charged in (1) to carboxylic acid charged in (1) is from about 1.0 to 2.0; additional Formula 3 compound is charged in (2); and the nominal mole ratio of the additional Formula 3 compound charged in (2) to carboxylic acid charged in (1) is from about 2.0 to 4.0.