1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 5-chloro-4-((2,2-dimethylchroman-7-yloxy)methyl)-2-fluoro-N-(N-methylsulfamoyl)benzamide

Participants

Reaction Steps

A mixture of 5-chloro-4-((2,2-dimethylchroman-7-yloxy)methyl)-2-fluorobenzoic acid (50 mg, 0.14 mmol), methyl(sulfamoyl)amine (23 mg, 0.21 mmol), 1-ethyl-(3-dimethylamino-propyl)carbodiimide hydrochloride (40 mg, 0.21 mmol) and 4-dimethylaminopyridine (26 mg, 0.21 mmol) in DCM (20 mL) was stirred at room temperature for 16 hrs. The mixture was diluted with HCl (2.0 N, 20 mL) and extracted with EtOAc (50×3 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by reverse phase Combiflash (18%-25% MeCN in 0.5% NH4HCO3) to give target product (35.4 mg, 56%) as a pale yellow solid. LCMS (ESI) Method A: RT=5.78 min, m/z: 456.7 [M+H]+; 1H-NMR (500 MHz, MeOH-d4,): δ 7.77 (d, J=6.0 Hz, 1H), 7.42 (d, J=10.5 Hz, 1H), 6.99 (d, J=8.5 Hz, 1H), 6.52 (dd, J=9.0, 2.5 Hz, 1H), 6.36 (d, J=2.5 Hz, 1H), 5.14 (s, 2H), 2.74 (t, J=6.5 Hz, 2H), 2.71 (s, 3H), 1.80 (t, J=6.5 Hz, 2H), 1.32 (s, 6H).

Provenance & Evidence