Reaktion #2011151

Reaktionsgleichung

(2S)-4-(benzyloxy)-2-{[(tert-butoxy)carbonyl]amino}-4-oxobutanoic acid

DIPEA

(2R)-2-amino-N-(quinolin-6-yl)-4-[4-(trifluoromethyl)phenyl]butanamide

TBTU

→

benzyl (3S)-3-{[(tert-butoxy)carbonyl]amino}-3-{[(1R)-1-[(quinolin-6-yl)carbamoyl]-3-[4-(trifluoromethyl)phenyl]propyl]carbamoyl}propanoate

Ausbeute 82.6%

Lösungsmittel

DCM

Reaktionsbedingungen

Aufarbeitung

1. 1
   WaschenThe reaction mixture was then washed with 1 M K2CO3, 1 M HCl, brine
2. 2
   Trocknendried over MgSO4
3. 3
   SonstigeThe residue was then purified on a silica gel column (50:1 CHCl3/methanol)

Vorschrift

To the solution of (2S)-4-(benzyloxy)-2-{[(tert-butoxy)carbonyl]amino}-4-oxobutanoic acid VIII (430 mg, 1.33 mmol) in DCM (10 mL) was added DIPEA (0.65 mL, 3.75 mmol), (2R)-2-amino-N-(quinolin-6-yl)-4-[4-(trifluoromethyl)phenyl]butanamide VII (540 mg 1.21 mmol) and TBTU (428 mg, 1.33 mmol). The mixture was stirred at r.t. overnight. The reaction mixture was then washed with 1 M K2CO3, 1 M HCl, brine and dried over MgSO4. The residue was then purified on a silica gel column (50:1 CHCl3/methanol) to yield benzyl (3S)-3-{[(tert-butoxy)carbonyl]amino}-3-{[(1R)-1-[(quinolin-6-yl)carbamoyl]-3-[4-(trifluoromethyl)phenyl]propyl]carbamoyl}propanoate IX (680 mg, 1.00 mmol, 75% yield). 1H NMR (CDCl3) 1.46 (s, 9H), 1.88-2.20 (m, 2H), 2.40-2.64 (m, 1H), 2.66-2.88 (m, 1H), 2.92 (d, J=6 Hz, 1H), 3.27 (dd, J=5 Hz, J=17 Hz, 1H), 4.49-4.70 (m, 2H), 5.12 (d, J=5 Hz, 2H), 5.59 (d, J=8 Hz, 1H), 7.07 (d, J=8 Hz, 1H), 7.22-7.42 (m, 8H), 7.53 (s, 1H), 7.57 (s, 1H), 7.72 (dd, J=2 Hz, J=9 Hz, 1H), 8.00 (d, J=9 Hz, 1H), 8.08 (d, J=8 Hz, 1H), 8.41 (d, J=2 Hz, 1H), 8.82 (d, J=4 Hz, 1H), 8.89 (s, 1H); 19F NMR (DMSO-d6) −61.73 (s, 3F); ESIMS found for C36H37F3N4O6 m/z 679 (M+H).

Quelle