N-[5-(Aminosulfonyl)-4-methyl-1,3-thiazol-2-yl]-N-methyl-2-[4-(2-pyridinyl)phenyl]acetamide mesylate monohydrate

摘要

The present invention relates to an improved and shortened synthesis of N-[5-(aminosulfonyl)-4-methyl-1,3-thiazol-2-yl]-N-methyl-2-[4-(2-pyridinyl)phenyl]acet-amide and the mesylate monohydrate salt thereof by using boronic acid derivatives or borolane reagents while avoiding toxic organic tin compounds and to the mesylate monohydrate salt of N-[5-(aminosulfonyl)-4-methyl-1,3-thiazol-2-yl]-N-methyl-2-[4-(2-pyridinyl)phenyl]acet-amide which has demonstrated increased long term stability and release kinetics from pharmaceutical compositions.

主权项

1. Method for synthesizing N-[5-(aminosulfonyl)-4-methyl-1,3-thiazol-2-yl]-N-methyl-2-[4-(2-pyridinyl)phenyl]acetamide according to the following steps:
Step A: Reacting compound A of the following general formula A* wherein
R1 represents a leaving group andR2 represents an alkyl residue with 1 to 6 carbon atoms or a cycloalkyl residue with 3 to 6 carbon atoms with a boronic acid derivative, borolane, borinane or diboronic acid reagent under elimination of R1—H or R1—B(OR)2 and formation of an intermediate boronic acid derivative of compound A, wherein the intermediate boronic acid derivative is then reacted with the pyridine compound B of the following general formula B* wherein
R3 represents a leaving group under basic conditions in order to directly obtain (4-pyridin-2-ylphenyl)acetic acid which is then purified. Step B: Reacting (4-pyridin-2-ylphenyl)acetic acid obtained from step A with 4-methyl-2-(methylamino)-1,3-thiazole-5-sulfonamide in order to obtain N-[5-(aminosulfonyl)-4-methyl-1,3-thiazol-2-yl]-N-methyl-2-[4-(2-pyridinyl)phenyl]acetamide of the formula