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

Participants

Reaction Conditions

Reaction Steps

To the solution of 4-bromo-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyridazin-3(2H)-one (5) (80 mg, 0.219 mmol) in toluene (5 mL) under N2, (5-chloro-6-methylpyridin-2-yl)methanamine (4) (50 mg, 0.320 mmol), Pd2(dba)3 (15 mg, 0.0219 mmol), BINAP (20 mg, 0.0328 mmol) and NaOt-Bu (42 mg, 0.438 mmol) were added. After the reaction mixture was stirred at 85° C. for 4 h, 15 mL water was added. The mixture was extracted with EtOAc (3×10 mL). The combined organics were dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by reverse phase chromatography (X bridge Prep C18OBD, 40-60% acetonitrile in water with 10 mmol NH4HCO3 modifier) to afford the compound as an oil (15 mg, 15.5% yield). 1H NMR (400 MHz, MeOD) δ 8.05-8.04 (s, 1H), 7.75-7.73 (d, 1H), 7.30-7.27 (m, 1H), 7.20-7.15 (m, 2H), 5.72 (s 1H), 4.40 (s, 2H), 4.18-4.14 (m, 1H), 4.10-4.00 (m, 1H), 3.86 (s, 3H), 3.71 (s, 3H), 2.61 (s, 3H), 2.08-2.03 (m, 1H), 1.75-1.70 (m, 1H), 1.18-1.13 (m, 1H) 1.03-0.95 (m, 1H); LRMS m/z (M+H) 441.1 found, 441.15 required.

Provenance & Evidence