Ammonium Chloride → 4-[4-[(5-Cyano-furan-2-carbonyl)-amino]-3-(4-methyl-piperidin-1-yl)-phenyl]-piperazine-1-carboxylic acid benzyl ester

Participants

Reaction Steps

A procedure similar to Example 9, step (c) was followed using 153 mg (0.349 mmol) of 4-[3-(4-methyl-piperidin-1-yl)-4-nitro-phenyl]-piperazine-1-carboxylic acid benzyl ester (as prepared in the previous step), 97.7 mg (1.75 mmol) of iron powder, 187 mg (3.49 mmol) of ammonium chloride in 10 mL of EtOH-water (2:1) to afford 104 mg (73%) of the corresponding aniline after chromatography on silica with 4-12% EtOAc-dichloromethane. The aniline (100 mg) together with 33.6 mg (0.245 mmol) of 5-cyanofuran-2-carboxylic acid (as prepared in Example 1), 42.7 μL (0.490 mmol) of oxalyl chloride, and 64.1 μL (0.368 mmol) of DIEA afforded, after chromatography on a 20-g silica SPE column with 2% EtOAc-dichloromethane, 118 mg (91%) of the title compound as a light yellow solid: 1H-NMR (CDCl3; 400 MHz): δ 9.59 (br s, H), 8.31 (d, 1H, J=8.9 Hz), 7.33-7.38 (m, 5H), 7.21, 7.24 (AB q, 2H, J=3.7 Hz), 6.79 (d, 1H, J=2.6 Hz), 6.72 (dd, 1H, J=8.9, 2.6 Hz), 5.17 (s, 2H), 3.66-3.69 (m, 4H), 3.12 (br s, 4H), 2.97-3.00 (m, 2H), 2.69-2.75 (m, 2H), 1.83-1.86 (m, 2H), 1.50-1.65 (m, 1H), 1.46-1.52 (m, 2H) and 1.07 (d, 3H, J=6.2 Hz). Mass spectrum (ESI, m/z): Calcd. for C30H33N5O4, 528.3 (M+H), found 528.1.

Provenance & Evidence