反应详情

To a solution of 2-[(2-chloro-6-methylphenyl)amino]-7,7-dimethyl-7,8-dihydro-1H-furo[3,2-e]benzimidazole-5-carboxylic acid (Intermediate-35, 0.100 g, 0.268 mmol) in benzene (2 mL), thionyl chloride (3.0 mL) was added at 5-10° C. and the reaction mass was refluxed for 3 h. To the reaction mixture, stirred solution of 4-trifluoromethyl phenyl amine (0.065 g, 0.403 mmol) and DIPEA (0.069 g, 0.534 mmol) in THF (10.0 mL) for 1 h at RT under N2-atmosphere was added and stirring was continued for another 1 h at RT. Excess of thionyl chloride was co-evaporated with THF under vacuum. Water was added to the reaction mass and it was extracted with ethyl acetate. The organic layer was separated, dried over anhydrous sodium sulphate and concentrated. The obtained crude product was purified by column chromatography on neutral alumina eluting with 0.7-1.0% MeOH:DCM to afford 0.012 g of the desired product. 1HNMR (DMSO-d6): δ 1.58 (s, 6H), 2.24 (s, 3H), 3.44 (s, 2H), 7.25-7.31 (m, 2H), 7.42 (d, J=7.2 Hz, 1H), 7.50 (s, 1H), 7.70 (d, J=8.7 Hz, 2H), 7.91 (d, J=8.4 Hz, 2H), 9.09 (s, 1H), 10.01 (s, 1H), 10.94 (s, 1H); MS [M−H]−: 513.42.

1. temperaturethe reaction mass was refluxed for 3 h
2. additionwas added
3. extractionwas extracted with ethyl acetate
4. customThe organic layer was separated
5. dry with materialdried over anhydrous sodium sulphate
6. concentrationconcentrated
7. customThe obtained crude product
8. customwas purified by column chromatography on neutral alumina eluting with 0.7-1.0% MeOH