Water → 3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-(4,5-dihydro-1H-imidazol-1-ylmethyl)thiophene-2-carboxamide

Participants

Reaction Steps

To N-(5-chloropyridin-2-yl)-2-[((4-(chloromethyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide (1.5 g, 3.0 mmol) in DMF (15 mL), was added ethylene diamine (0.09 g, 15 mmol) at ambient temperature. After 2 hours, the reaction was poured into water and extracted with ethyl acetate. The ethyl acetate solution was dried (NaSO4) and concentrated in vacuo to afford the crude amine adduct. To the adduct was added triethyl orthoformate (1.33 g, 9 mmol) in acetic acid (20 mL). After stirring at ambient temperature for 1 hour, the reaction was poured into water and extracted with ethyl acetate. The ethyl acetate layer was dried (NaSO4), concentrated in vacuo, and purified by HPLC on a C18 Dynamax column with acetonitrile in water gradient with 0.1 % trifluoroacetic acid to afford 0.87 g of N-(5-chloropyridin-2-yl)-2-[((4-((imidazolin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide (870 mg), trifluoroacetic acid salt; NMR (DMSO-d6 /TFA) 10.9 (s, 1), 10.3 (s., 1 ), 9.4 (s, 1), 8.6 (d, 2), 8.3 (d, 1), 8.1 (d, 1), 7.8 (dd, 1), 7.3 (d, 1), 7.2 (d, 1), 4.6 (s, 2), 3.7~3.9 (m, 7) ppm.

Provenance & Evidence