反应详情

To a solution of ethyl((1S)-5-{3-[[2-chloro-5-(4-methoxyphenyl)-4-pyrimidinyl](methyl)amino]propoxy}2,3-dihydro-1H-inden-1-yl)acetate (Example 443, 70 mg, 0.137 mmol) in a mixture of THF (2 mL), ethanol (1 mL), and water (2 mL) was added LiOH.H2O (13 mg, 0.55 mmol). The mixture was maintained at rt in an orbital shaker for 16 h after which the reaction mixture was washed with Et2O. To the remaining aqueous solution was added HCl (1 N aqueous solution) dropwise until pH 5 was reached. The aqueous solution was then extracted with EtOAc, the combined organic layers dried (Na2SO4), filtered, and concentrated under reduced pressure to give 20 mg (30%) of the product as a white solid. 1H NMR (400 MHz, CDCl3): δ 1.75-1.79 (m, 1H), 2.18-2.21 (m, 2H), 2.24-2.49 (m, 2H), 2.77-2.90 (m, 3H), 3.31 (s, 3H), 3.52-3.74 (m, 1H), 3.92 (s, 3H), 3.99 (t, 2H), 4.05 (t, 2H), 6.67 (d, 1H), 6.75 (s, 1H), 6.94 (d, 2H), 7.08 (s, 1H), 8.15 (s, 1H), 8.27 (d, 2H); LC-MS: RT=2.91 min, (M+H)+ 482.2.

1. washwas washed with Et2O
2. additionTo the remaining aqueous solution was added HCl (1 N aqueous solution) dropwise until pH 5
3. extractionThe aqueous solution was then extracted with EtOAc
4. dry with materialthe combined organic layers dried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure