1,1-Dichloroethane → (3S*,5R*)-5-(3-Benzyl-ureido)-piperidine-3-carboxylic acid cyclopropyl-[1-(3-methoxy-propyl)-1H-indol-3-ylmethyl]-amide

Participants

Reaction Conditions

Reaction Steps

A mixture of (3R*,5S*)-3-amino-5-{cyclopropyl-[1-(3-methoxy-propyl)-1H-indol-3-ylmethyl]-carbamoyl}-piperidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester (91 mg, 0.15 mmol), dichloroethane (2 mL) and benzyl isocyanate (18.4 μL, 0.15 mmol) is shaken for 14 h at 50° C. A second portion of benzyl isocyanate (9.2 μL, 0.075 mmol) is added and shaking is continued for 5 h at 60° C. The mixture is evaporated in vacuo. The crude product is stirred with a solution of CH2Cl2/piperidine 4:1 (5 mL) for 2 h, the mixture is evaporated and the residue purified by preparative HPLC (C18 column, 10-100% CH3CN+0.1% TFA/H2O+0.1% TFA, 20 min, flow 20 mL/min). The combined pure fractions are treated with K2CO3, CH3CN is removed in vacuo and the residual aqueous phase extracted three times with CH2Cl2. The combined organic layers are dried (Na2SO4) and evaporated to afford the title compound as a yellow resin. MS: 518.3 [M+H]+; tR (HPLC, Nucleosil C18; 5-100% CH3CN+0.1% TFA/H2O+0.1% TFA for 8 min, flow 1.5 ml/min): 5.05 min.

Provenance & Evidence