反应详情

A mixture of {3-[(S)-3-cyclopentyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-propionylamino]-pyrazol-1-yl}-acetic acid tert-butyl ester (133 mg, 0.26 mmol, prepared as in Example 3) and lithium hydroxide monohydrate (22 mg, 0.52 mmol) in tetrahydrofuran:water (1:1, 10 mL) at room temperature was stirred for 2 h. The reaction mixture was then concentrated in vacuo and partitioned between a 1 N aqueous hydrochloric acid solution and ethyl acetate. The organic layer was then dried over magnesium sulfate, filtered to remove the drying agent, and the filtrate concentrated in vacuo to afford {3-[(S)-3-cyclopentyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-propionylamino]-pyrazol-1-yl}-acetic acid (118 mg, 98%) as a white foam: HR-ES(+) m/e calcd for C22H23N4O4F3 [M+H]+ 465.1744, observed 465.1744; 1H NMR (400 MHz, DMSO-d6) δ ppm 10.93 (s, 1H), 8.01 (dd, J=7.67, 13.00 Hz, 2H), 7.69-7.80 (m, 1H), 7.59 (d, J=2.13 Hz, 1H), 6.45 (d, J=2.13 Hz, 1H), 4.95-5.12 (m, 2H), 4.81 (s, 2H), 4.72 (d, J=17.90 Hz, 1H), 1.09-2.11 (m, 11H).

1. concentrationThe reaction mixture was then concentrated in vacuo
2. custompartitioned between a 1 N aqueous hydrochloric acid solution and ethyl acetate
3. dry with materialThe organic layer was then dried over magnesium sulfate
4. filtrationfiltered
5. customto remove the drying agent
6. concentrationthe filtrate concentrated in vacuo