1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → ((S)-2-[(S)-5-(6-Chloro-4-methyl-9H-beta-carbolin-8-ylcarbamoyl)-2,2-dimethyl-morpholin-4-yl]-1-methyl-ethyl)-carbamic acid tert-butyl ester

Participants

Reaction Steps

A solution of (S)-4-((S)-2-tert-butoxycarbonylamino-propyl)-6,6-dimethyl-morpholine-3-carboxylic acid (3.316 g, 10.5 mmol) (prepared by reductively alkylating (S)-6,6-dimethyl-morpholine-3-carboxylic acid with N-(tert-butoxycarbonyl)-L-alanal) in anhydrous pyridine (75 mL) was stirred at room temperature. 6-chloro-4-methyl-9H-β-carbolin-8-ylamine (1.869 g, 8.09 mmol) was added, followed by EDCI (2.894 g, 15.1 mmol). The reaction was stirred at room temperature for 14-18 hours under argon. The reaction was partially concentrated, diluted with H2O (20 mL) and transferred to a separatory funnel. The mixture was diluted with brine (50 mL) and extracted with EtOAc (3×100 mL). The combined organic layers were washed with brine, dried, filtered and concentrated to afford a dark residue. Column chromatography (0-8% MeOH/CH2Cl2) yielded ((S)-2-[(S)-5-(6-Chloro-4-methyl-9H-β-carbolin-8-ylcarbamoyl)-2,2-dimethyl-morpholin-4-yl]-1-methyl-ethyl)-carbamic acid tert-butyl ester as a light tan solid (2.688 g). 1H-NMR (300 MHz, DMSO-d6): δ 11.25 (s, 1) 9.94 (s, 1) 8.88 (s, 1) 8.18 (s, 1) 8.02 (s, 1) 7.92 (s, 1) 6.73 (d, 1) 3.95-3.85 (m, 2) 3.66 (br s, 1) 3.16-3.08 (m, 1) 2.88 (d, 1) 2.76 (s, 3) 2.51-2.40 (m, 1) 2.23 (dd, 1) 1.99 (d, 1) 1.34 (br s, 12) 1.17 (s, 3) 1.08 (d, 3). NH4OAc standard conditions. ELSD Rf=2.07 min. M+H=530.

Provenance & Evidence