2-Methylbenzenesulfonic acid hydrate → 4-(9-cyclohexyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(1-methyl-piperidin-4-yl)-benzamide

Participants

Reaction Steps

A mixture of 0.0562 g (0.17 mmole) 2-chloro-9-cyclohexyl-7,7-difluoro-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-246), 0.0485 g (0.255 mmole) of toluenesulfonic acid monohydrate, 0.0397 g (0.17 mmole) of 4-amino-N-(1-methyl-piperidin-4-yl)-benzamide and 1 mL of isopropanol was heated in a sealed vessel at 140 degrees for 15 hours, cooled and concentrated under reduced pressure. The residue taken up in ethyl acetate and washed successively with 50 mL of saturated aqueous sodium bicarbonate, 50 mL of water, 50 mL of brine. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was recrystallized from acetonitrile to give 0.0501 g of 4-(9-cyclohexyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(1-methyl-piperidin-4-yl)-benzamide (I-262) as a white solid.

Provenance & Evidence