Methanol → Tert-butyl 4-(1-(3,4-dichlorophenyl)-3-(hydroxymethyl)-6-oxo-1,6-dihydropyridazin-4-yloxy)piperidine-1-carboxylate

Participants

Reaction Steps

To a mixture of 4-(1-(tert-butoxycarbonyl)piperidin-4-yloxy)-1-(3,4-dichlorophenyl)-6-oxo-1,6-dihydropyridazine-3-carboxylic acid (from example 15 step A) (5 mg, 0.01 mmol) in THF (1 ml) at room temperature under argon was added 1 M BH3 in THF (31 uL, 0.031 mmol). The reaction mixture was stirred at room temperature for one hour. Methanol (2 mL) was carefully added to the reaction mixture and stirred at room temperature for two hours. Solvents were removed in vacuo. EtOAc (10 mL) and 1 N NaOH (10 mL) were added to the reaction mixture. Layers were separated. Organic layer were washed with water (10 mL), and brine (10 mL). Organic phase was dried (MgSO4), filtered and concentrated. The crude product was purified by preparative HPLC (C18 column; 10-100% methanol in water without TFA) to give tert-butyl 4-(1-(3,4-dichlorophenyl)-3-(hydroxymethyl)-6-oxo-1,6-dihydropyridazin-4-yloxy)piperidine-1-carboxylate (2.3 mg, gum, 42.6%). 1H NMR (400 MHz, CDCl3) δ ppm 1.45-1.48 (m, 9H) 1.68-1.93 (m, J=3.95 Hz, 2H) 1.88-2.17 (m, 2H) 2.65-2.84 (m, 1H) 3.27-3.46 (m, 2H) 3.55-3.76 (m, 2H) 4.43-4.60 (m, 1H) 4.67 (s, 2H) 6.08-6.35 (m, 1H) 7.40-7.62 (m, 2H) 7.63-7.83 (m, 1H). MS (ESI) 414 (M+H-tBu).

Provenance & Evidence