Triethylamine → 5-Cyano-furan-2-carboxylic acid [2-(4-methyl-piperidin-1-yl)-4-(1,2,3,6-tetrahydro-pyridin-4-yl)-phenyl]-amide dihydrochloride

Participants

Reaction Conditions

Reaction Steps

A flask was charged with 5-cyano-furan-2-carboxylic acid (0.015 g, 0.10 mmol) (as prepared in Example 1), DCM (1 mL), DMF (5 μL), and oxalyl chloride (10 μL, 0.11 mmol) and stirred at 25° C. for 1 h and then concentrated. The resulting 5-cyano-furan-2-carbonyl chloride was dissolved in DCM (1 mL) and added to a solution of 4-[4-amino-3-(4-methyl-piperidin-1-yl)-phenyl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (0.040 g, 0.10 mmol) (as prepared in the previous step) and NEt3 (25 μL, 0.15 mmol) in DCM (1 mL) at 0° C. The solution was allowed to attain RT and stirred for 10 h. The intermediate BOC protected compound was eluted from a 5-g SPE cartridge (silica) with 20% EtOAc/hexane, and then dissolved in DCM (1 mL) and TFA (0.30 mL) and stirred at 25° C. for 30 min. The reaction was concentrated and purified by RP-HPLC (C18), eluting with a linear gradient of 40% CH3CN to 70% CH3CN in 0.1% TFA/H2O over 10 min to give the title compound as a di-TFA salt. This product was then eluted from a 10-g column of BioRad AG-2X8 resin (chloride ion form) with methanol to give 0.017 g (37%) of the title compound. 1H-NMR (400 MHz, DMSO-d6): δ 9.81 (s, 1H), 9.40 (br s, 2H), 8.18 (d, 1H), 7.82 (d, 1H), 7.50 (d, 1H), 7.36 (s, 1H), 7.28 (d, 1H), 6.22 (m, 1H), 3.76 (m, 2H), 3.46 (3, 3H), 2.98 (m, 2H), 2.74 (m, 6H), 1.82 (m, 2H), 1.50 (m, 3H), 1.00 (d, 3H), Mass spectrum (ESI, m/z): Calcd. for C23H26N4O2, 391.2 (M+H), found 391.2.

Provenance & Evidence