N,N-Dimethylethylenediamine → 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)-N-(2-dimethylamino-ethyl)-3-trifluoromethyl-benzamide

Participants

Reaction Steps

To a mixture of 0.125 g (0.257 mmole) 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)-3-trifluoromethyl-benzoic acid (I-204) and 9 mL of dimethylformamide was added 0.0521 g (0.386 mmole) of 1-hydroxybenzotriazole, 0.146 g (0.385 mmole) of 1-[bis(dimethylamino)methylene]-1H-benzotriazolium-3-oxide hexafluorophosphate and 0.140 g (1.081 mmole) of diisopropylethylamine. The mixture was stirred for 10 minutes, then 0.034 g (0.385 mmole) of N,N-dimethylethylenediamine was added. The reaction mixture was stirred for 2 hours and then concentrated under reduced pressure. The residue was dissolved in 80 mL of ethyl acetate and washed three times with 10 mL of 1M sodium hydroxide, twice with 15 mL of brine, dried, filtered and concentrated under reduced pressure. Purification by silica gel chromatography, eluting with dichloromethane-methanol (gradient, 95:5-80:20) gave 0.1188 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)-N-(2-dimethylamino-ethyl)-3-trifluoromethyl-benzamide (I-208) as a white solid.

Provenance & Evidence