4-Amino-2-fluoro-5-methoxybenzoic acid → 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-2-fluoro-5-methoxybenzoic acid

Participants

Reaction Steps

2-Chloro-9-cyclopentyl-7,7-difluoro-5-methyl-8,9-dihydro-5H-pyrimido[5,4-b][1,4]diazepin-6(7H)-one (158 mg, 0.5 mmol), 4-amino-2-fluoro-5-methoxy benzoic acid (obtained above), i-PrOH (5 mL) and conc. HCl (10 drops) were heated to 100° C. overnight. The reaction mixture was then cooled to room temperature. The reaction mixture contains desired product plus lots of de-carboxylation byproduct, which were separated by RP-HPLC to give the product as a white solid (12 mg). [M+H] calc'd for C21H22F3N5O4, 466. found 466.

Provenance & Evidence