Triethylamine → 1-{[1-(2-aminopyrimidin-4-yl)-6-iodo-1H-indazol-3-yl]carbonyl}azetidin-3-ol

Participants

Reaction Steps

To a solution of 1-(2-amino-pyrimidin-4-yl)-6-iodo-1H-indazole-3-carboxylic acid (500 mg, 1.08 mmol) in DMF (5 ml) was added HATU (823.46 mg, 2.17 mmol) followed by azetidin-3-ol HCl (237.26 mg, 2.17 mmol) and triethylamine (0.45 ml, 3.25 mmol). The reaction mixture was stirred at RT for 3 hr. A white precipitate was also observed which was not soluble in EtOAc and water. The solid was filtered and washed with EtOAc and the filtrate worked up. The solid was dried and analysed by LCMS found to be clean title compound. To the filtrate water (6 ml) was added and the product extracted into EtOAc (2×10 ml). The combined organics were washed with water and brine and concentrated in vacuo. The material was then purified by column chromatography, (9:1 DCM: methanol). The combined column fractions were then triturated from acetonitrile to give the title compound; 1H NMR (500 MHz, DMSO) 3.86 (1H, dd, J=10.56, 3.94 Hz), 4.26-4.46 (2H, m), 4.52-4.64 (1H, m), 4.88 (1H, dd, J=9.77, 7.25 Hz), 5.83 (1H, d, J=6.62 Hz), 7.10 (1H, d, J=5.36 Hz), 7.17 (2H, br. s), 7.77 (1H, d, J=8.51 Hz), 8.04 (1H, d, J=8.51 Hz), 8.36 (1H, d, J=5.67 Hz), 9.34 (1 H, s). LC-MS: m/z=+436.95 (M+H)+.

Provenance & Evidence