Process for preparing acylsulfamoylbenzamides
View Patent ↗The invention relates to a process for the preparation of a compound of formula (I): Which comprises reaction of a compound of formula (II) with a compound of the formula (III) in the presence of a chlorinating agent, followed by reaction of the resultant compound of the formula (IV) with a compound of formula (V) in the presence of a base: wherein the various symbols are as defined in claim 1.
1. A compound of formula (IV):
in which R 3 and R 5 are each independently halogen, (C 1 -C 6 )-alkyl, (C 1 -C 6 )-haloalkyl, (C 1 -C 6 )-alkoxy, S(O) q —(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkylcarbonyl, —CO-aryl, cyano or nitro; or two adjacent R 5 groups form a —O—CH 2 CH 2 — moiety,
R 4 is hydrogen, (C 1 -C 4 )-alkyl, (C 2 -C 4 )-alkenyl or (C 2 -C 4 )-alkynyl,
n is an integer from 0 to 4,
m is an integer from 0 to 5, and
q is 0, 1 or 2; or a salt thereof.
2. A compound or a salt thereof as claimed in claim 1 , wherein
R 3 is each independently halogen, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-haloalkyl, (C 1 -C 4 )-alkoxy, S(O) q —(C 1 -C 4 )-alkyl, cyano or nitro,
R 4 is hydrogen or (C 1 -C 4 )-alkyl,
R 5 is each independently halogen, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-haloalkyl, (C 1 -C 4 )-alkoxy, cyano or nitro,
n is 0, 1 or 2,
m is 0 or 1 or 2, and
q is 0, 1 or 2.
3. A compound or a salt thereof as claimed in claim 1 , wherein
R 4 is hydrogen,
R 3 is (C 1 -C 6 )-alkoxy,
n is 0,
m is 0 or 1,
and the sulfamoyl group is located para to the COCl moiety in the phenyl ring.
4. A compound or a salt thereof as claimed in claim 1 , wherein
R 4 is hydrogen,
R 5 is (C 1 -C 4 )-alkoxy,
n is 0,
m is 1,
and the sulfamoyl group is located para to the COCl moiety in the phenyl ring.
5. A process for the preparation of a compound of formula (IV), or a salt thereof, as defined in claim 1 , which comprises reaction of a compound of formula (II):
wherein R 3 , R 4 and n are as defined in formula (IV),
with a compound of formula (III):
wherein R 5 and m are as defined in formula (IV) and Y is OH or Cl, in the presence of a chlorinating agent.
6. A process as claimed in claim 5 wherein Y is OH.
7. A process as claimed in claim 5 wherein the chlorinating agent is thionylchloride.
8. A process as claimed in claim 5 wherein the amount of chlorinating agent used is, when Y is OH from 1 to 2 molar equivalents per equivalents of (II) and (IIIa), or when Y is Cl from 1 to 2 molar equivalents per equivalent of (II).
9. A process as claimed in claim 5 , wherein the solvent used in the reaction of the compound of formula (II) with the compound of formula (III) is chlorobenzene.
10. A process for the preparation of a compound of formula (I) or a salt thereof,
wherein:
R 1 is hydrogen, —(CH 2 ) p -heterocyclyl or a hydrocarbon radical, where the two last-mentioned radicals are unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, (C 1 -C 6 )-alkyl, (C 1 -C 6 )-haloalkyl, (C 1 -C 6 )-alkoxy, cyano and nitro;
R 2 is hydrogen, (C 1 -C 6 )-alkyl, (C 2 -C 6 )-alkenyl, (C 2 -C 6 )-alkynyl, (C 1 -C 6 )-alkoxy, (C 2 -C 6 )-alkenyloxy, where the five last-mentioned radicals are unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, (C 1 -C 4 )-alkoxy and (C 1 -C 4 )-alkylthio; or
R 1 and R 2 together with the linking nitrogen atom form a 3- to 8-membered saturated or unsaturated ring;
R 3 and R 5 are each independently halogen, (C 1 -C 6 )-alkyl, (C 1 -C 6 )-haloalkyl, (C 1 -C 6 )-alkoxy, S(O) q —(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkylcarbonyl, —CO-aryl, cyano or nitro; or two adjacent R 5 groups form a —O—CH 2 CH 2 — moiety;
R 4 is hydrogen, (C 1 -C 4 )-alkyl, (C 2 -C 4 )-alkenyl or (C 2 -C 4 )-alkynyl;
n is an integer from 0 to 4;
m is an integer from 0 to 5;
p is 0 or 1; and
q is 0, 1 or 2; or a salt thereof,
which process comprises the reaction of a compound of formula (IV),
in which R 3 , R 4 , R 5 m and n are defined as in formula (I),
with a compound of formula (V):
R 1 R 2 NH (V)
wherein R 1 , R 2 , R 3 , R 4 , R 5 , m and n are as defined in formula (I),
in the presence of a base.
11. A process as claimed in claim 10 , wherein
R 3 is each independently halogen, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-haloalkyl, (C 1 -C 4 )-alkoxy, S(O) q —(C 1 -C 4 )-alkyl, cyano or nitro,
R 4 is hydrogen or (C 1 -C 4 )-alkyl,
R 5 is each independently halogen, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-haloalkyl, (C 1 -C 4 )-alkoxy, cyano or nitro,
n is 0, 1 or 2,
m is 0 or 1 or 2, and
q is 0, 1 or 2.
12. A process as claimed in claim 10 , wherein
R 4 is hydrogen,
R 5 is (C 1 -C 6 )-alkoxy,
n is 0,
m is 0 or 1,
and the sulfamoyl group is located para to the COCl moiety in the phenyl ring.
13. A compound or a salt thereof as claimed in claim 1 ,
wherein R 3 is (C 5 -C 6 )-haloalkyl, S(O) q —(C 1 -C 6 )-alkyl, (C 5 -C 6 )-alkylcarbonyl, —CO-aryl; or two adjacent R 5 groups form a —O—CH 2 CH 2 — moiety.
14. A compound or a salt thereof as claimed in claim 1 ,
wherein R 5 is (C 5 -C 6 )-haloalkyl, S(O) q —(C 1 -C 6 )-alkyl, (C 5 -C 6 )-alkylcarbonyl, —CO-aryl; or two adjacent R 5 groups form a —O—CH 2 CH 2 — moiety.
15. A compound or a salt thereof as claimed in claim 1 ,
wherein R 3 and R 5 are each independently (C 5 -C 6 )-haloalkyl, S(O) q —(C 1 -C 6 )-alkyl, (C 5 -C 6 )-alkylcarbonyl, —CO-aryl; or two adjacent R 5 groups form a —O—CH 2 CH 2 — moiety.