反应详情

温度

40 °C

A solution of 12N HCl:MeOH (1:1, 6 ml) was added to 7-[(3aS,4R,6R,6aR)-6-[({4-[6-chloro-5-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl]butyl}(methyl)amino)methyl]-2,2-dimethyl-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-N-cyclopropyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine at 0° C. The mixture was stirred at 40° C. for 5 hrs, a further aliquot of HCl (12N, 1 ml) was added to the reaction mixture and continued at 40° C. for a further 1 h. This was then evaporated in vacuo. The residue was dissolved in DCM (100 ml) and MeOH (1 ml), washed with sat. NaHCO3 (2×50 ml), dried over Na2SO4, filtered and evaporated. Purification by prep.TLC, eluting with 7N NH3 in MeOH:DCM (5:95, then 2×1:9) gave the desired product. AcCl(5 eq) was added slowly to MeOH (1 ml) at 0° C., this was then added to a solution of the above product in MeOH and stirred for 5 mins before concentrating. Water (1 ml) was added and then lyophilized to give a white solid (129 mg, 81%); MS (ESI+) for C28H33ClF3N7O2 m/z 592.20 [M+H]+; HPLC purity 99% (ret. time, 2.61 min); 1H NMR (500 MHz, MeOD) δ ppm 8.33 (1H, s), 8.21 (1H, s), 8.07 (1H, s), 7.62 (1H, d, J=3.47 Hz), 6.91 (1H, br. s.), 5.04-5.14 (1H, m), 4.33 (1H, t, J=6.38 Hz), 4.10-4.21 (1H, m), 3.38-3.65 (3H, m), 3.31-3.37 (3H, m), 2.98 (3H, d, J=4.89 Hz), 2.85 (1H, br. s.), 2.44-2.63 (2H, m), 1.94-2.11 (4H, m), 1.88 (1H, q, J=11.24 Hz), 1.07-1.15 (2H, m), 0.81-0.89 (2H, m).

1. waitcontinued at 40° C. for a further 1 h
2. customThis was then evaporated in vacuo
3. dissolutionThe residue was dissolved in DCM (100 ml)
4. washMeOH (1 ml), washed with sat. NaHCO3 (2×50 ml)
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. customevaporated
8. customPurification by prep.TLC,
9. washeluting with 7N NH3 in MeOH:DCM (5:95