Dimethylacetamide → 6-cyano-1-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide

Participants

Reaction Conditions

Reaction Steps

To 20 mL microwave vial containing a mixture of 6-bromo-1-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide (0.25 g, 0.564 mmol), zinc cyanide (0.066 g, 0.564 mmol), zinc (7.37 mg, 0.113 mmol), and dppf (0.063 g, 0.113 mmol) was added N,N-Dimethylacetamide (DMA) (5.0 mL). The suspension was stirred with degassing under nitrogen for 5 min. Next added PdCl2(dppf)-CH2Cl2 adduct (0.046 g, 0.056 mmol). The reaction contents were sealed and stirred with heating at 135° C. (heat block) for 16 h. The reaction mixture was allowed to cool to RT, diluted with 80 mL of water, and adjusted to pH˜8 with sat NaHCO3. The contents were stirred for 30 min, filtered, and the filter cake was washed with water. The collected solid was dried under hi vacuum for 4 h. The crude product was dissolved in DCM/MeOH followed by addition of silica gel, and concentrated in vacuo to dryness. The contents were purified by silica gel chromatography (dry loaded; eluent: 2-65% gradient of 10% methanol in dichloromethane and dichloromethane). The product was concentrated from MTBE and dried in hi-vac oven for 6 h at 45° C. to afford the title compound as 0.190 g (85%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.64-1.75 (m, 2H) 1.83-1.93 (m, 2H) 1.94-2.06 (m, 2H) 2.10-2.19 (m, 5H) 2.21 (s, 3H) 4.35 (d, J=4.80 Hz, 2H) 5.31 (t, J=7.07 Hz, 1H) 5.89 (s, 1H) 7.91 (d, J=1.26 Hz, 1H) 8.51 (s, 1H) 8.60 (s, 1H) 8.66 (t, J=4.93 Hz, 1H) 11.54 (s, 1H); LC-MS (ES) m/z=390.2 [M+H]+

Provenance & Evidence