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

Participants

Reaction Conditions

Reaction Steps

To a 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), benzophenone imine (0.142 mL, 0.846 mmol) and Cs2CO3 (0.735 g, 2.256 mmol) was added 1,4-dioxane (5 mL) and the suspension stirred with degassing under N2 for 5 min. Next added Xantphos (0.098 g, 0.169 mmol), degassed for 5 min, and then added Pd2(dba)3 (0.077 g, 0.085 mmol) and degassed for 1 min. The reaction vial was sealed and the mixture heated at 100° C. (heat block) with stirring for 2 h. The contents were cooled to RT, diluted with water (80 mL), and extracted with EtOAc (2×). The combined organic layers were dried over MgSO4, filtered through Celite, and concentrated in vacuo. The crude solid was dissolved in THF (5 mL) and treated with HCl (0.564 mL, 1.692 mmol). The volatiles were removed in vacuo. The residue was dried under hi-vacuum, and then dissolved in MeOH/DCM followed by addition of silica gel. The contents were concentrated to dryness and dried under hi-vacuum for 1 h. The contents were purified by silica gel chromatography (dry loaded, eluent: 3-95% gradient chloroform (containing 10% 2M ammonia in methanol) and DCM). The collected solid was triturated from hot acetonitrile, and then placed in freezer for 15 min. The contents were filtered cold and washed with additional acetonitrile. The title compound was collected as 90 mg (41%); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.60-1.72 (m, 2H), 1.78-1.89 (m, 2H), 1.91-2.00 (m, 2H), 2.01-2.10 (m, 2H), 2.12 (s, 3H), 2.22 (s, 3H), 4.32 (d, J=5.05 Hz, 2H), 4.84 (t, J=7.07 Hz, 1H), 5.41 (s, 2H), 5.88 (s, 1H), 6.65 (s, 1H), 6.88 (d, J=1.52 Hz, 1H), 7.95 (s, 1H), 8.14 (t, J=5.18 Hz, 1H), 11.53 (s, 1H); LC-MS (ES) m/z=379.2 [M+H]

Provenance & Evidence