Hydrochloric Acid → HCID 10297013, compound

Participants

Reaction Steps

To a 25 mL round-bottomed flask at rt was charged with 4-{2-(ethoxycarbonyl)-1-[(3-methoxyphenyl)methyl]indol-3-yl}benzoic acid (Example 98, 270 mg, 0.63 mmol), tetrahydrofuran (2 mL) and one drop of N,N-dimethylformamide. Oxalyl chloride (240 mg, 0.16 mL, 1.89 mmol) was added to the above mixture dropwise. After 1 hour, the reaction mixture was concentrated and re-dissolved in tetrahydrofuran (2 mL) and cyclopropylamine (359 mg, 6.3 mmol) was added. After 10 minutes at rt, aqueous sodium hydroxide (3 N) was added to the reaction mixture and enough methanol was added to make the mixture one phase. The resulting solution was refluxed for 1 hour before it was cooled to rt and acidified with hydrochloric acid (1N) and extracted with ethyl acetate (25 mL). The organic layer was washed with water, brine and dried over anydrous sodium sulfate. The solution was concentrated in vacuo to give a white solid which was triturated with diethyl ether to provide 3-[4-(N-cyclopropylcarbamoyl)phenyl]-1-[(3-methoxyphenyl)methyl]indole-2-carboxylic acid as a white solid (142 mg, 51%): mp 237° C.; MS (electrospray, MH+) calcd for C27H25N2O4 441, found 441; 1H NMR (DMSO-d6) δ 13.1 (br s, 1H), 8.48 (d, J=4.0 Hz, 1H), 7.88 (d, J=8.3 Hz, 2H), 7.62 (d, J=8.4 Hz, 1H), 7.50 (d, J=8.6 Hz, 2H), 7.46 (d, J=8.1 Hz, 1H), 7.30-7.37 (m, 1H), 7.12-7.22 (m, 2H), 6.79 (dd, J=8.2, 2.5 Hz, 1H), 6.69 (dd, 1H), 6.62 (d, J=7.6 Hz, 1H), 5.83 (s, 2H), 3.68 (s, 3H), 2.85-2.89 (m, 1H), 0.56-0.64 (m, 2H), 0.65-0.75 (m, 2H).

Provenance & Evidence