1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 86680512, compound

Participants

Reaction Steps

A mixture of the product from Example 54F (100 mg, 0.300 mmol), 2-(4-bromo-3-(trifluoromethyl)phenyl)acetic acid (127 mg, 0.450 mmol), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (115 mg, 0.600 mmol), hydroxybenzotriazole hydrate (92 mg, 0.600 mmol), and diisopropylethylamine (0.262 mL, 1.500 mmol) in dichloromethane (3.0 mL) was stirred at room temperature for 3 hours. The mixture was partitioned between water and ethyl acetate, and the organic extract was dried over Na2SO4. The mixture was filtered, concentrated and dried in vacuo, and the residue was dissolved in anhydrous N,N-dimethylformamide (2 mL). Copper(I) cyanide (0.11 g, 1.228 mmol) was added, and the resulting mixture was stirred at 130° C. under N2 for 2 days. The mixture was allowed to cool to room temperature and was partitioned between water (10 mL) and ethyl acetate (4×10 mL). The organic layers were combined and dried over Na2SO4, filtered and concentrated in vacuo to give a crude product that was purified by column chromatography on silica gel using a solvent gradient of 0-10% methanol in dichloromethane. The title compound was obtained as a colorless solid (45 mg, 32%). 1H NMR (300 MHz, CDCl3) δ ppm 0.84-1.05 (m, 4 H), 1.80-2.07 (m, 3 H), 2.13-2.53 (m, 3.5 H), 2.73-3.10 (m, 2 H), 3.22-3.35 (m, 0.5 H), 3.63-3.99 (m, 4 H), 4.53-4.80 (m, J=38.32, 12.55 Hz, 1 H), 5.31-5.42 (m, 1 H), 7.56 (d, J=7.80 Hz, 1 H), 7.67 (s, 1 H), 7.80 (d, J=8.14 Hz, 1 H), 7.92-7.95 (m, 1 H), 8.00-8.05 (m, J=1.36 Hz, 1 H); MS (ESI) m/z 472 (M+H)+.

Provenance & Evidence