L-Valine → N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-6-(methylsulfonyl)-1H-indazole-4-carboxamide

Participants

Reaction Conditions

Reaction Steps

To a 10 mL microwave vial containing a stirring mixture of L-valine (8.42 mg, 0.072 mmol), NaOH (0.024 mL, 0.072 mmol), and DMSO (1.6 mL) were added sodium methanesulfinate (0.065 g, 0.539 mmol), copper(I) iodide (6.85 mg, 0.036 mmol) and 1-Ethyl-3-methylimidazoliym bromide (0.014 g, 0.072 mmol). After stirring for 15 min, 6-bromo-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-indazole-4-carboxamide (0.15 g, 0.359 mmol) was added. The reaction vial was sealed and the mixture was stirred with heating at 90° C. (heat block) for 18 h. The contents were then irradiated (microwave) at 130° C. for 2 hr. After cooling to RT, the reaction mixture was poured onto 50 mL of water and stirred. The contents were extracted with hot 30% THF/EtOAc (2×) (need to heat to break up emulsion). The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography (eluent: 5-75% chloroform (containing 10% 2M ammonia in methanol) and dichloromethane. The isolated product was concentrated from DCM and MTBE, and dried under hi vacuum. The title compound was collected as 75 mg (49%); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.50 (d, J=6.57 Hz, 6H) 2.13 (s, 3H) 2.22 (s, 3H) 3.30 (s, 3H) 4.38 (d, J=4.80 Hz, 2H) 5.23 (quin, J=6.57 Hz, 1H) 5.90 (s, 1H) 8.02 (d, J=1.01 Hz, 1H) 8.45 (s, 1H) 8.52 (s, 1H) 8.77 (t, J=4.80 Hz, 1H) 11.56 (s, 1H); LCMS: (M+H)+=417.1.

Provenance & Evidence