Binap, (A+-)- → 2-methyl-6-(((1S,2S)-2-(1-methyl-1H-pyrazol-3-yl)cyclopropyl)methoxy)-4-((2-methylthiazol-5-yl)methylamino)pyridazin-3(2H)-one

Participants

Reaction Conditions

Reaction Steps

To the solution of 4-bromo-2-methyl-6-(((1S,2S)-2-(1-methyl-1H-pyrazol-3-yl)cyclo propyl)methoxy)pyridazin-3(2H)-one (made according to Example 1, by replacing ((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methanol with ((1S,2S)-2-(1-methyl-1H-pyrazol-3-yl)cyclopropyl)methanol, 27 mg, 0.08 mmol) in toluene (2 mL) under N2, (2-methylthiazol-5-yl)methanamine (13 mg, 0.096 mmol), Pd2(dba)3 (7 mg, 0.008 mmol), BINAP (7 mg, 0.012 mmol) and NaOtBu (9 mg, 0.096 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 MgSO4, 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 title compound as an oil. 1H NMR (400 MHz, MeOD) δ 7.56 (s, 1H), 7.42 (d, 1H), 5.96 (d, 1H), 5.89 (s, 1H), 4.59 (s, 2H), 4.15-5.11 (m, 1H), 4.04-4.01 (m, 1H), 3.81 (s, 3H), 3.63 (s, 3H), 2.66 (s, 3H), 1.95-1.89 (m, 1H), 1.61-1.53 (m, 1H), 1.01-0.95 (m, 2H); LRMS m/z (M+H) 387.1 found, 387.15 required.

Provenance & Evidence