反应详情

A solution of tert-butyl (5-(6-(((1R,2S)-2-((tert-butoxycarbonyl)amino)cyclo-hexyl)amino)-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yl)-1,3-thiazol-2-yl)carbamate (41.5 mg, 0.058 mmol) in TFA (5 mL) was heated to 65° C. for 3 h. After removal of the solvent, the resulting crude material was reconstituted in MeOH/DMF (6.0 mL) and purified via preparative HPLC eluting with water (0.05% TFA) and ACN (10-20% gradient, 0.035% TFA). The collected fractions were stripped to dryness via rotary evaporation to yield the title compound as a TFA salt (6.7 mg, 32%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.12-2.11 (m, 9 H), 3.73 (br s, 2 H), 4.19 (d, J=3.79 Hz, 1 H), 4.41 (d, J=3.03 Hz, 2 H), 6.95 (d, J=3.03 Hz, 1 H), 7.77 (br s, 2 H), 8.44 (s, 1 H), 8.93 (s, 1 H). [M+H] calc'd for C16H19FN6OS, 363; found, 363.

1. customAfter removal of the solvent
2. custompurified via preparative HPLC
3. washeluting with water (0.05% TFA) and ACN (10-20% gradient, 0.035% TFA)
4. customThe collected fractions were stripped to dryness via rotary evaporation