Acetaldehyde → HCID 71657866, compound

Participants

Reaction Conditions

Reaction Steps

The above obtained mixture of tert-butyl 2-(6-amino-2-(4-fluorophenyl)-5-(4-methoxy-3-((1-(pyrimidin-2-yl)cyclopropyl)carbamoyl)phenyl)benzofuran-3-yl)-1H-imidazole-1-carboxylate and 5-(6-amino-2-(4-fluorophenyl)-3-(1H-imidazol-2-yl)benzofuran-5-yl)-2-methoxy-N-(1-(pyrimidin-2-yl)cyclopropyl)benzamide (170 mg, 0.257 mmol) in MeOH (25 mL) was cooled to 0° C. and then added with acetaldehyde (45.3 mg, 1.029 mmol). The reaction mixture was allowed to warm to rt and stirred for 45 min. The reaction mixture was again cooled to 0° C. and then added with sodium cyanoborohydride (32.3 mg, 0.515 mmol). The reaction mixture was allowed to warm to rt and stirring continued at rt for 2 hr. The reaction mixture was concentrated completely at reduced pressure at 35° C. The residue was diluted with water and 10% NaHCO3 solution, filtered, and the solid obtained dried under suction. The crude product was purified by preparative HPLC to separate the two compounds. 1H NMR (400 MHz, DMSO-d6) δ ppm: 12.32 (br s, 1H) 8.92 (s, 1H) 8.69 (d, J=4.8 Hz, 2H) 7.94-8.03 (m, 2H) 7.86 (d, J=2.51 Hz, 1H) 7.55 (dd, J=8.53, 2.51 Hz, 1H) 7.22-7.33 (m, 5H) 7.21 (s, 1H) 7.13 (s, 1H) 6.91 (s, 1H) 4.58 (t, J=5.65 Hz, 1H) 3.99 (s, 3H) 3.13-3.22 (m, 2H) 1.59-1.66 (m, 2H) 1.38-1.46 (m, 2H) 1.10-1.21 (m, 3H). 19F NMR (376.6 MHz, DMSO-d6) δ ppm: 112.76. LCMS: (ES−) m/z=587.2 (M−H); Column—Acentis Express C8 (50×2.1 mm; 2.7 u); M phase A: 2% MeCN-98% H2O-10 mM NH4COOH; M phase B: 98% MeCN-2% H2O-10 mM NH4COOH

Provenance & Evidence