Hydrochloride methanol → Ammonia

Participants

Reaction Conditions

Reaction Steps

A solution of 12N aq. HCl:MeOH (1:1, 3 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}(propan-2-yl)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., stirred at 40° C. for 4 hrs. Upon completion, the reaction mixture was concentrated in vacuo. The residue was dissolve in DCM (100 ml) and MeOH (1 ml). This was washed with sat. NaHCO3 (2×50 ml), dried over Na2SO4, filtered and evaporated. Purification by prep.TLC, eluting with MeOH:DCM (1:9) and then 7N NH3 in MeOH:DCM (5:95) gave the desired product. This was then dissolved in MeOH (1 ml). To this was added HCl (4M in dioxane, 5 eq), shaken for 5 mins and evaporated to dryness. This was then re-dissolved in Water (1 ml) and MeOH (3 drops) and lyophilised to give an off white solid (100 mg, 55%); MS (ESI+) for C30H37ClF3N7O2 m/z 620 [M+H]+: HPLC purity>95% (ret. time, 1.35 min): 1H NMR (500 MHz, MeOD) δ ppm 8.31 (1H, s), 8.16 (1H, s), 8.01 (1H, br. s.), 7.59 (1H, d, J=3.31 Hz), 6.91 (1H, br. s.), 5.08 (1H, br. s.), 4.30 (1H, t, J=5.91 Hz), 4.16 (1H, br. s.), 3.85 (1H, br. s.), 3.38-3.59 (2H, m), 2.85 (1H, br. s.), 2.52 (2H, br. s.), 1.93-2.21 (4H, m), 1.86 (1H, s), 1.32-1.52 (6H, m), 1.00-1.24 (2H, m), 0.73-1.00 (2H, m).

Provenance & Evidence