Triethylamine → HCID 68181680, compound

Participants

Reaction Steps

To a solution of 1-(2-amino-5-chloropyrimidin-4-yl)-6-[(3R)-3-hydroxy-3-(5-methyl-1,2,4-oxadiazol-3-yl)but-1-yn-1-yl]-1H-indazole-3-carboxylic acid (100 mg at 65% purity, 0.14 mmol) in DMF (3 mL) was introduced O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (105 mg, 0.28 mmol), azetidin-3-ol hydrochloride (30 mg, 0.28 mmol) and triethylamine (0.06 mL, 0.42 mmol). After 5 hr at RT, the reaction mixture was retreated with O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (105 mg, 0.28 mmol), azetidin-3-ol hydrochloride (30 mg, 0.28 mmol) and triethylamine (0.06 mL, 0.42 mmol). The reaction was given a further 1 hr at RT, then diluted with water (2 ml) and extracted with EtOAc (2×5 mL extractions). The combined organic extracts were washed with water (5 mL) and brine (5 ml), dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by silica gel flash column chromatography (DCM containing a 2-12% gradient of methanol) furnished a solid which was suspended in acetonitrile (2 mL). Filtration furnished the title compound as a colorless solid: 1H NMR (500 MHz, DMSO-d6) delta 1.86 (3H, s), 2.62 (3H, s), 3.85 (1H, dd, J=10.9, 4.1 Hz), 4.19-4.45 (2H, m), 4.45-4.67 (1H, m), 4.71-4.97 (1H, m), 5.80 (1H, s), 6.76 (1H, s), 7.26-7.58 (3H, m), 8.02-8.35 (2H, m), 8.54 (1H, s); LC-MS: m/z=+495.05/497.10 (M+H)+.

Provenance & Evidence