反应详情

To a solution of 4-(3-methyl-1H-pyrazol-1-yl)-2-trifluoromethyl benzoic acid (1.1 g, 4.1 mmole) of Step C, and triethylamine (0.57 mL, 4.1 mmol) in dichloromethane (20 mL) was added 2,4,6-trichlorobenzoyl chloride (0.63 mL, 4.0 mmol). After stirring for 5.5 hours, 6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine of Example 1, Step B (0.67 g, 3.4 mmol) and 4-dimethylamino pyridine (0.42 g, 3.4 mmol) were added. After stirring for an additional 18 hours, the mixture was poured into saturated aqueous sodium bicarbonate. The organic phase was washed with brine, dried over sodium sulfate, and evaporated to dryness. The residue was dissolved in dichloromethane and absorbed onto a silica Merck-60 flash column. Elution with hexane-ethyl acetate (gradient from 8:2 to 7:3) provided the title product (0.89 g) as a foam which crystallized by sonication from ethanol-hexane, m.p. 212-214° C. This material was identical to the compound of Example 4, Step C.

1. stirringAfter stirring for an additional 18 hours
2. washThe organic phase was washed with brine
3. dry with materialdried over sodium sulfate
4. customevaporated to dryness
5. dissolutionThe residue was dissolved in dichloromethane
6. customabsorbed onto a silica Merck-60 flash column
7. washElution with hexane-ethyl acetate (gradient from 8:2 to 7:3)