Benzamide, 3-bromo-N-cyclopropyl-4-fluoro- (9CI) synthesis

Yield:639858-63-2 93.3%

Reaction Conditions:

Stage #1: 3-bromo-4-fluorobenzoic acidwith triethylamine;N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate in N,N-dimethyl-formamide at 10; for 0.5 h;
Stage #2: Cyclopropylamine in N,N-dimethyl-formamide at 10; for 14 h;

Steps:

36 3-bro o-A-cy cl opropy 1 -4-fl uorobenza i de

To a solution of 3-bromo-4-fluorobenzoic acid (500 mg, 2.28 mmol) and Et₃N (0.953 mL, 6.85 mmol) in DMF (3 mL) was added HATU (868 mg, 2.28 mmol). The mixture was stirred at 10°C for 30 minutes. Cyclopropanamine (0.158 mL, 2.28 mmol) was added. The reaction mixture was stirred at 10°C for 14 hours, and then water (20 mL) was added, forming a precipitate. The solids were isolated by filtration. The filter cake was triturated with a mixture of petroleum ether (5 mL) and EtOAc (50 mL) to give the title compound as a yellow solid (550 mg, 93.3%). NMR (400 MHz, CDCh) d ppm 0.61 - 0.65 (m, 2 H) 0.84 - 0.91 (m, 2 H) 2.87 - 2.91 (m, 1 H) 6.33 (d, =72.8 Hz, 1 H) 7.14 - 7.27 (m, 1 H) 7.71 - 7.68 (m, 1 H) 7.95 - 7.98 (m, 1 H).

References:

WO2020/198053,2020,A1 Location in patent:Paragraph 0345-0346