Diisopropylethylamine → HCID 178513428, compound

Participants

Reaction Steps

Hydroxylamine hydrochloride (36 mg) is added to 2-(2-ethyl-imidazol-1-yl)-pyrimidine-5-carboxylic acid (1-cyano-piperidin-4-yl)-cyclopropyl-amide (180 mg, Intermediate 32) and ethyldiisopropylamine (0.1 mL) in ethanol (30 mL) and the mixture is refluxed for 4 h. Another 10 mg hydroxylamine hydrochloride is added and the mixture is refluxed for 1 h and stirred at room temperature for 12 h. The solvent is removed in vacuo to yield the respective (N-hydroxycarbamimidoyl)-piperidine derivative as an intermediate. Subsequently 50 mg of the aforementioned intermediate are added to tetrahydrofuran (10 mL) followed by ethyldiisopropylamine (32 μL) and cyclopropanecarbonyl chloride (11 μL). The mixture is stirred at room temperature for 1.5 h. Acetonitrile is added and the mixture is refluxed for 5 h. The mixture is concentrated and 1,2-dicholorethane (2.0 mL) and (methoxycarbonylsulfamoyl) triethylammonium hydroxide (Burgess reagent, 75 mg) are added and the mixture is heated in a microwave oven to 130° C. for 15 min. The solvent is removed in vacuo and the residue is purified by HPLC (MeOH/H2O/TFA) to yield the desired product. LC (method 9): tR=1.09 min; Mass spectrum (ESI+): m/z=449 [M+H]+.

Provenance & Evidence