4-Methylmorpholine → tert-butyl N-[(1S)-2-[bis(2-{[(tert-butoxy)carbonyl]amino}ethyl)carbamoyl]-1-{[(1R)-1-[(quinolin-6-yl)carbamoyl]-3-[4-(trifluoromethyl)phenyl]propyl]carbamoyl}ethyl]carbamate

Participants

Reaction Steps

To a solution of CDMT (37 mg, 0.20 mmol) in DCM (10 mL) and cooled to 0° C. was added N-methylmorpholine (0.023 mL, 0.20 mmol). The mixture was stirred for min before adding (3S)-3-{[(tert-butoxy)carbonyl]amino}-3-{[(1R)-1-[(quinolin-6-yl)carbamoyl]-3-[4-(trifluoromethyl)phenyl]propyl]carbamoyl}propanoic acid (110 mg, 0.18 mmol). The solution was stirred for 60 min at 0° C. The tert-butyl N-{2-[(2-{[(tert-butoxy)carbonyl]amino}ethyl)amino]ethyl}carbamate X was then added and the mixture stirred at r.t. overnight. The solution was washed with 1 M aq. K2CO3, 1 M aq. HCl, brine and dried over anhydrous MgSO4. The crude product was then purified on a silica gel column (100:1 CHCl3/MeOH) and finally crystallized from ethyl ether/hexane to give tert-butyl N-[(1S)-2-[bis(2-{[(tert-butoxy)carbonyl]amino}ethyl)carbamoyl]-1-{[(1R)-1-[(quinolin-6-yl)carbamoyl]-3-[4-(trifluoromethyl)phenyl]propyl]carbamoyl}ethyl]carbamate XI (110 mg, 0.13 mmol, 72% yield). 1H NMR (CDCl3) 1.43 (s, 18H), 1.50 (s, 9H), 1.69 (brs, 2H), 2.03 (brs, 2H), 2.78 (brs, 2H), 3.23 (brs, 2H), 3.46 (brs, 4H), 4.60 (brs, 4H), 4.96-5.11 (m, 1H), 5.98-6.14 (m, 1H), 6.91-7.01 (m, 1H), 7.28-7.38 (m, 3H), 7.47-7.58 (m, 3H), 7.88-8.03 (m, 2H), 8.12 (d, J=7 Hz, 1H), 8.52 (s, 1H), 8.81 (brs, 1H), 9.31 (brs, 1H); 19F NMR (DMSO-d6) −61.75 (s, 3F); ESIMS found for C43H58F3N7O9 m/z 874 (M+H).

Provenance & Evidence