Process for preparing 2-amino-5-cyanobenzoic acid derivatives

摘要

Disclosed is a method for preparing a compound of Formula 1 comprising contacting a compound of Formula 2 with at least one compound of Formula 3 in the presence of a solvent comprising one or more organic solvents selected from ethers and nitriles and a catalytically effective amount of a palladium complex comprising at least one tertiary phosphine ligand of Formula 4;
wherein R1 is NHR3 or OR4; R2 is CH3 or Cl; R3 is H, alkyl, cyclopropyl, cyclopropylmethyl or methylcyclopropyl; R4 is H or C1-C4 alkyl; M1 is an alkali metal; and R5, R6 and R7 are defined in the disclosure; provided that when R2 is Cl, then X is Br. Also disclosed is a method for preparing a compound of Formula 5 wherein R14, R15, R16 and Z are as defined in the disclosure using a compound of Formula 1 characterized by preparing the compound of Formula 1 by the aforedescribed method.
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主权项

1. A method for preparing a compound of Formula 1 wherein
R1 is NHR3 or OR4;R2 is Cl or CH3;R3 is H, C1-C4 alkyl, cyclopropyl, cyclopropylmethyl or methylcyclopropyl; andR4 is H or C1-C4 alkyl; comprising contacting (1) a compound of Formula 2 wherein X is Br or Cl; with (2) at least one compound of Formula 3
M1CN  3 wherein M1 is an alkali metal in the presence of (3) a solvent comprising one or more organic solvents selected from ethers and nitriles; and (4) a catalytically effective amount of a palladium complex comprising at least one tertiary phosphine ligand selected from the group consisting of benzyl-di-1-adamantylphosphine, di-tert-butylneopentylphosphine or tri-tert-butylphosphine; provided that when R2 is Cl, then X is Br; and when X is Cl, then the tertiary phosphine ligand is tri-tert-butylphosphine.