Aniline → 5-cyano-N-(2-(4-methylpiperidin-1-yl)-4-morpholinophenyl)furan-2-carboxamide

Participants

Reaction Steps

The procedure of Example 4, step (c) was followed using 101 mg (0.331 mmol) of 4-[3-(4-methyl-piperidin-1-yl)-4-nitro-phenyl]-morpholine (as prepared in the previous step) and 40 mg of 10% palladium on carbon (50% by weight water) in 5 mL THF to prepare the corresponding aniline. However, 5-cyanofuran-2-carboxylic acid N-hydroxysuccinimide ester was used to acylate the aniline instead of 5-cyanofuran-2-carbonyl chloride. (5-cyanofuran-2-carboxylic acid N-hydroxysuccinimide ester was previously prepared from 5-cyanofuran-2-carboxylic acid (as prepared in Example 1), oxalyl chloride, N-hydroxysuccinimide and DIEA following the procedure of Example 4, step (c).) The aniline prepared above in 3.0 mL of anh dichloromethane was treated with 77.5 mg (0.331 mmol) of 5-cyanofuran-2-carboxylic acid N-hydroxysuccinimide ester. After stirring for 1 h, an additional 77.5 mg (0.331 mmol) of 5-cyanofuran-2-carboxylic acid N-hydroxysuccinimide ester was added. After 3 h, a final 77.5 mg (0.331 mmol) of 5-cyanofuran-2-carboxylic acid N-hydroxysuccinimide ester was added and the mixture stirred 18 h. Concentration in vacuo and chromatography on a 10-g silica SPE column with 2-4% EtOAc-dichloromethane afforded 85.1 mg (65%) of the title compound as a light yellow solid: 1H-NMR (CDCl3; 400 MHz): δ 9.60 (br s, 1H), 8.32 (d, 1H, J=8.9 Hz), 7.22, 7.26 (AB q, 2H, J=3.7 Hz), 6.78 (d, 1H, J=2.7 Hz), 6.71 (dd, 1H, J=8.9, 2.7 Hz), 3.86-3.88 (m, 4H), 3.13-3.15 (m, 4H), 2.98-3.01 (m, 2H), 2.70-2.15 (m, 2H), 1.83-1.86 (m, 2H), 1.5-1.7 (br m, 1H) and 1.43-1.53 (m, 2H). Mass spectrum (ESI, m/z): Calcd. for C22H26N4O3, 395.2 (M+H), found 395.2.

Provenance & Evidence