Acetic Acid → HCID 57794534, compound

Participants

Reaction Steps

Solid NaCNBH3 (38.3 mg, 0.614 mmol) was added to a stirred solution of (2S)-2-amino-3-[4-({4-[3-chloro-2-fluoroanilino]-6-methoxyquinazolin-7-yl}oxy)piperidin-1-yl]-3-oxopropan-1-ol (150 mg, 0.307 mmol, Example 15), sodium acetate trihydrate (251 mg, 3.07 mmol), formaldehyde 37% (aq) (2.5 ml) and acetic acid (184 mg, 3.07 mmol) at 0-5° C. The resulting solution was allowed to warm to room temperature and stir for 1 hour. The mixture was then evaporated and the resulting yellow residue was purified by flash chromatography on silica gel eluting with increasingly polar mixtures of dichloromethane/7N ammonia in methanol (100/0-85/15). Fractions containing the desired product were combined and evaporated to give the title compound as a white solid (26%); 1H NMR Spectrum: 1.52-1.69 (m, 2H), 1.94-2.07 (m, 2H), 2.28-2.30 (2 x s, 6H), 3.15-3.22 (m, 2H), 3.53-3.76 (m, 4H), 3.94 (s, 3H), 4.02 (m, 1H), 4.49 (m, 1H), 4.92-4.94 (m, 1H), 7.27(dd, 1H), 7.34 (s, 1H), 7.47 (dd, 1H), 7.51 (dd, 1H), 7.81 (s, 1H), 8.38 (s, 1H), 9.65 (s, 1H); Mass Spectrum: (M+H)+ 518.

Provenance & Evidence