Formaldehyde → HCID 11525433, compound

Participants

Reaction Steps

Molecular sieves (0.5 g) followed by aqueous formaldehyde (1 ml) were added to a stirred solution of (2R,4R)-4-({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}oxy)piperidine-2-carboxamide (9) (0.102 g, 0.23 mmol) in DCM-AcOH (10:1 ml) at room temperature. The reaction mixture was stirred for 1-2 minutes before solid sodium triacetoxyborohydride (0.10 g, 0.463 mmol) was added portionwise over 5 minutes. The reaction was essentially complete after all the sodium triacetoxyborohydride reducing agent had been added. DCM was added (20 ml) and the reaction was carefully neutralised with saturated aqueous NaHCO3(aq). The organic extract was washed with brine, dried (MgSO4) and concentrated to a yellow foam. The residue was purified by preparative LCMS (standard basic conditions) to give the title product as a white solid (0.85 g, 80%): 1H NMR Spectrum: (DMSO d6) 1.87-1.92 (m, 3H), 2.07-2.09 (m, 1H), 2.20 (s, 3H), 2.43-2.47 (m, 1H), 2.71-2.80 (m, 2H), 3.96 (s, 3H), 4.82 (m, 1H), 7.03 (s, 1H), 7.23 (s, 1H), 7.26-7.30 (m, 2H), 7.47-7.54 (m, 2H), 7.82 (s, 1H), 8.37 (s, 1H), 9.60 (s, 1H); Mass Spectrum: (M+H)+ 459.9.

Provenance & Evidence