Ammonia → Methyl 3-(carbamoylamino)benzoate

Participants

Reaction Steps

3-Isocyanato-benzoic acid methyl ester (500 mg, 2.82 mmol) was treated with 0.5 M NH3 in dioxane (20 mL). The mixture was agitated for 48 h, and the product, 3-ureido-benzoic acid methyl ester (200 mg, 1.03 mmol), was isolated by filtration as a white solid (404 mg, 73.7%). This intermediate was dissolved in methanol (2 mL) and Amberlyst A26® (OH− form) was added. The resulting mixture was agitated overnight. The resin was then filtered and washed with methanol (3×2 mL). The product was eluted with a solution of 20% formic acid in methanol (3×2 mL) and the resin was washed with methanol (1 mL) and DMF (2×2 mL). The combined eluant solvents were evaporated to provide 139 mg (75% yield) of the urea 3-ureido-benzoic acid. This reagent was then coupled with 3-aminomethyl-N-(4-dimethylaminomethyl-phenyl)-benzamide using the same coupling procedure described in Example 14 to provide the title compound; MS, electrospray, 446 (M+H)

Provenance & Evidence