反应详情

To a stirred solution of the 10-{[2-methoxy-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of Step E (0.300 g, 0.65 mmol)) in N,N-dimethylformamide (15 mL) was added 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.150 g, 0.78 mmol) and 1-hydroxybenzotriazole (0.110 g, 0.78 mmol). After the solution became homogeneous 3-methylamino-1,2-propanediol (0.082 g, 0.78 mmol) was added, and the solution was stirred at room temperature overnight. The mixture was then poured into water and extracted with ethyl acetate. The combined ethyl acetate layers were washed with water, dried and concentrated to dryness. The residue was subjected to silica chromatography eluting with 10% methanol in chloroform. The pure fractions were concentrated and the residue azeotroped and triturated several times with hexane to provide the title product (0.118 g) as a white solid, m.p. 119-123° C.

1. additionwas added
2. extractionextracted with ethyl acetate
3. washThe combined ethyl acetate layers were washed with water
4. customdried
5. concentrationconcentrated to dryness
6. washeluting with 10% methanol in chloroform
7. concentrationThe pure fractions were concentrated
8. customthe residue azeotroped
9. customtriturated several times with hexane