Tetrahydrofuran → HCID 178483558, compound

Participants

Reaction Conditions

Reaction Steps

171.3 μL of piperidylcarbonyl chloride and 200 μL of N,N-diisopropylethylamine are added to a solution of 100 mg of intermediate 1 in 10 mL of THF. The reaction mixture is heated at 52° C. for 48 hours. The reaction medium is cooled to ambient temperature and then 20 mL of a saturated solution of sodium bicarbonate are added. The aqueous phase is extracted with 3 times 10 mL of EtOAc. The organic phases are dried over MgSO4, filtered and concentrated under vacuum in a rotary evaporator. The reaction crude is purified by flash chromatography on an Intelliflash apparatus on an Analogix RS-4 cartridge. Elution is carried out with a dichloromethane/methanol mixture. 28 mg of piperidine-1-carboxylic acid [3-[6-(3-dimethylaminopropoxy)-5-fluoro-1H-benzimidazol-2-yl]-1-(tetrahydropyran-2-yl)-1H-pyrazol-4-yl]amide are obtained in the form of a brown resin. 1H NMR (300 MHz, DMSO-d6, δ in ppm): 1.50 to 2.36 (m, 14H); 2.29 (broad s, 6H); 2.55 (m partially masked, 2H); 3.50 (m, 4H); 3.66 (m, 1H); 3.96 (m, 1H); 4.11 (m, 2H); 5.46 (broad d, J=10.0 Hz, 1H); from 7.08 to 7.55 (m, 2H); 8.14 (broad s, 1H); from 9.66 to 9.93 (m, 1H); 13.05 (m, 1H).

Provenance & Evidence