Ammonium formate → HCID 86679985, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-methyl-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepan-4-ol (212 mg, 0.83 mmol) in MeOH (15 mL) was added ammonium formate (386 mg, 5.63 mmol) and 10% palladium on carbon (88 mg, 0.83 mmol) and the mixture was heated at 80° C. for 18 hr. The mixture was filtered through Celite® and the filtrate concentrated under reduced pressure. The residue was partitioned between DCM (20 mL) and water (20 mL) and the aqueous layer was re-extracted with DCM (3×20 mL). The combined organic layers were passed through a phase separation cartridge and concentrated under reduced pressure to give 1-(4-amino-1-methyl-1H-pyrazol-5-yl)-4-methylazepan-4-ol as a red oil. To a solution of this oil (140 mg, 0.623 mmol) in DCM (25 mL) was added 2-bromo-5-(tert-butoxycarbonylamino)thiazole-4-carboxylic acid (241 mg, 0.75 mmol), PyBOP (454 mg, 1.94 mmol) and DIPEA (0.17 mL, 1.0 mmol) and the mixture was stirred at room temperature for 16 hr. Water (20 ml) was added and the mixture was diluted with DCM (100 mL). The organic layer was washed with water (20 mL), separated, dried over MgSO4 and the solvent removed under reduced pressure. Purification via silica gel column chromatography (0-100% EtOAc/isohexane) gave tert-butyl 2-bromo-4-(5-(4-hydroxy-4-methylazepan-1-yl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)thiazol-5-ylcarbamate as an off-white solid (280 mg, 63% over two steps). 1H NMR (400 MHz, CDCl3) δ 10.49 (s, 1H), 9.41 (s, 1H), 7.95 (s, 1H), 3.71 (s, 3H), 3.41-3.30 (m, 1H), 3.24-3.11 (m, 3H), 2.39 (br s, 1H), 2.07-1.75 (m, 5H), 1.84-1.78 (m, 1H), 1.52 (s, 9H), 1.43 (s, 3H).

Provenance & Evidence