Binap, (A+-)- → 4-((4,5-dimethylthiazol-2-yl)methylamino)-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyridazin-3(2H)-one

Participants

Reaction Conditions

Reaction Steps

A mixture of (4,5-dimethylthiazol-2-yl)methanamine (28 mg, 0.2 mmol), 4-bromo-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyridazin-3(2H)-one (73 mg, 0.2 mmol), Pd2(dba)3 (18 mg, 0.02 mmol), BINAP (18 mg, 0.03 mmol) and t-BuONa (38 mg, 0.4 mmol) in toluene (4 mL) under N2 was heated at 85° C. for 4 h. filtered and concentrated to give crude product which was purified by Pre-HPLC to give the title compound 6 as a oil. 1H NMR (400 MHz, CD3OD) δ 7.92 (d, 1H), 7.14 (dd, 1H), 7.02 (d, 1H), 5.66 (s, 1H), 4.45 (d, 2H), 4.05-4.01 (m, 1H), 3.92-3.88 (m, 1H), 3.71 (s, 3H), 3.51 (s, 3H), 2.18 (s, 3H), 2.15 (s, 3H), 1.95-1.90 (m, 1H), 1.63-1.58 (m, 1H), 1.06-1.01 (m, 1H), 0.91-0.86 (m, 1H), LCMS m/z (M+H) 428.1 found, 428.1 required.

Provenance & Evidence