Diisopropylethylamine → ((3R*,5R*)-5-{Cyclopropyl-[1-(3-methoxy-propyl)-1H-indol-3-ylmethyl]-carbamoyl}-piperidin-3-yl)-carbamic acid tert-butyl ester

Participants

Reaction Steps

An ice-cooled mixture of (3R*,5R*)-5-tert-butoxycarbonylamino-piperidine-1,3-dicarboxylic acid 1-(9H-fluoren-9-ylmethyl) ester (93.3 mg, 0.2 mmol), O-(1H-6-chlorobenzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HCTU) (91 mg, 0.22 mmol) and ethyldiisopropylamine (17.1 μL, 0.1 mmol) in CH2Cl2/CH3CN 1:1 (2 mL) is stirred for 10 min. Cyclopropyl-[1-(3-methoxy-propyl)-1H-indol-3-ylmethyl]-amine (51.7 mg, 0.2 mmol) in CH2Cl2/CH3CN 1:1 (1 mL) is added and the mixture is stirred for 14 h at RT. The mixture is diluted with ethyl acetate, and washed twice with K2CO3 solution. The organic layer is dried over Na2SO4 and evaporated in vacuo. The crude product is treated with CH2Cl2/piperidine 4:1 (5 mL) and stirred for 1 h at RT. After evaporation in vacuo, the residue is purified by preparative HPLC (YMC Pack Pro C18, 10-100% CH3CN+0.1% TFA/H2O+0.1% TFA, flow 20 mL/min). The combined pure fractions are treated with solid K2CO3, CH3CN is removed in vacuo, and the residual aqueous phase is extracted twice with CH2Cl2. The combined organic layers are dried (Na2SO4) and evaporated to afford the title compound. MS: 485.5 [M+H]+; tR (HPLC, Nucleosil C18; 5-100% CH3CN+0.1% TFA/H2O+0.1% TFA for 8 min, flow 1.5 ml/min): 5.33 min.

Provenance & Evidence