Cesium carbonate → Methyl 4-((9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-B][1,4]diazepin-2-YL)amino)-2-fluoro-5-methoxybenzoate

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Reaction Steps

To a mixture of 0.67 g (0.0021 mole) of 2-chloro-9-cyclopentyl-7,7-difluoro-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-20), 0.63 g (0.00317 mole) of 4-amino-2-fluoro-5-methoxy-benzoic acid methyl ester and 30 mL of dioxane was added 0.05 g (0.00021 mole) of palladium (II) acetate and 1.91 g (0.00588 mole) of cesium carbonate. The mixture was stirred at room temperature for 5 minutes and then heated to 100 degrees for 18 hours. The solid was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was diluted with ethyl acetate, washed with water then brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with hexanes-ethyl acetate (60:40) to give 0.81 g of 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-methoxy-benzoic acid methyl ester (I-168).

Provenance & Evidence