Oxalyl chloride → 4,5-Dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid (2-chloro-4-methylcarbamoyl-phenyl)-methyl-amide

Participants

Reaction Conditions

Reaction Steps

4,5-Dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid ethyl ester was prepared according to Example 136 for 226, and hydrolyzed to the corresponding acid using General Procedure B. To a suspension of 4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid (130 mg) in dry dichloromethane (10 mL) was added oxalyl chloride (78 μL) and DMF (1 drop). After 1 hour the solvent was reduced in vacuo and the residue was dissolved in acetonitrile (10 mL) and to this was added 3-chloro-N-methyl-4-methylamino-benzamide from Example 21 (116 mg) and sodium bicarbonate (49 mg). The reaction mixture was warmed to 60° C. After 3 hours the reaction mixture was cooled, diluted with dichloromethane, washed with water, dried (MgSO4) and the solvent removed in vacuo. The residue was recrystallized form ethyl acetate/methanol/hexane to yield 121 (132 mg). NMR: (CDCl3): 3.04 (3H,d), 3.31 (2H,t), 3.48 (3H,s), 4.28-4.31 (2H,m), 6.05 (1H,sbr.), 6.81-6.83 (1H,m), 6.96 (1H,d), 7.05-7.15 (2H,m), 7.48 (1H,d), 7.78 (1H,dd), 7.93 (1H,s). MS: (ESI+) MH+ 428

Provenance & Evidence