反应详情

To a suspension of 0.0262 g (0.000062 mole) of 4-[(9-cyclopentyl-6,7,8,9-tetrahydro-5-methyl-6-oxospiro[5H-pyrimido[4,5-b][1,4]diazepine-7,1′-cyclopropan]-2-yl)amino]-3-methylbenzoic acid (I-60) in 3 mL of dimethylformamide was added 0.0144 g (0.000107 mole) of 1-hydroxybenzotriazole, 0.0365 g (0.000096 mole) of 1-[bis(dimethylamino)methylene]-1H-benzotriazolium 3-oxide hexafluorophosphate and 0.07 mL (0.000402 mole) of ethyldiisopropylamine. The mixture was stirred for 20 minutes and then 0.012 g (0.0001 mole) of 4-amino-1-methylpiperidine was added. The mixture was stirred for an additional 2.5 hours and then concentrated under reduced pressure. The residue was dissolved in ethyl acetate and washed successively with 1 M sodium hydroxide, brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with dichloromethane-methanol (98:2-80:20) to give 0.021 g of 4-[(9-cyclopentyl-6,7,8,9-tetrahydro-5-methyl-6-oxospiro[5H-pyrimido[4,5-b][1,4]diazepine-7,1′-cyclopropan]-2-yl)amino]-3-methyl-N-(1-methyl-4-piperidinyl)benzamide (I-61)

1. stirringThe mixture was stirred for an additional 2.5 hours
2. concentrationconcentrated under reduced pressure
3. dissolutionThe residue was dissolved in ethyl acetate
4. washwashed successively with 1 M sodium hydroxide, brine
5. dry with materialdried over anhydrous sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified by silica gel chromatography
9. washeluting with dichloromethane-methanol (98:2-80:20)