1,2-Dichloroethane → N-(tert-butoxycarbonyl)-4-methyl-D-leucyl-N-[2-(1H-tetraazol-1-yl)-5-(trifluoromethyl)benzyl]-L-prolinamide
Reaction equation
Cl.[N:2]1([C:7]2[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][C:8]=2[CH2:9][NH:10][C:11](=[O:17])[C@@H:12]2[CH2:16][CH2:15][CH2:14][NH:13]2)[CH:6]=[N:5][N:4]=[N:3]1.[C:26]([O:30][C:31]([NH:33][C@@H:34]([C:40](O)=[O:41])[CH2:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:32])([CH3:29])([CH3:28])[CH3:27].C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[C:26]([O:30][C:31]([NH:33][C@@H:34]([C:40]([N:13]1[CH2:14][CH2:15][CH2:16][C@H:12]1[C:11]([NH:10][CH2:9][C:8]1[CH:18]=[C:19]([C:22]([F:25])([F:23])[F:24])[CH:20]=[CH:21][C:7]=1[N:2]1[CH:6]=[N:5][N:4]=[N:3]1)=[O:17])=[O:41])[CH2:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:32])([CH3:29])([CH3:28])[CH3:27]Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 2
Procedure
A mixture of N-[2-(1H-tetraazol-1-yl)-5-(trifluoromethyl)benzyl]-L-prolinamide hydrochloride (35 mg, 0.09 mmol), N-(tert-butoxycarbonyl)-4-methyl-D-leucine (24 mg, 0.10 mmol), EDC (27 mg, 0.14 mmol), HOAt (6.3 mg, 0.05 mmol) and Hünig's base (34 mL, 0.20 mmol) in DMF (1.2 mL) was stirred at room temperature for 16 h. The title compound was isolated by extractive workup (EtOAc) and silica gel chromatography (60%-80% EtOAc-hexanes) as an oily foam which was carried on directly to the deprotection step. 1H NMR (400 MHz, CDCl3): δ 9.20 (s, 1H), 7.88 (s, 1H), 7.78 (br m, 1H), 7.71 (d, J=8.2 Hz, 1H), 7.45 (d, J=8.0 Hz, 1H), 4.97 (d, J=6.0 Hz, 1H), 4.59 (d, J=6.4 Hz, 1H), 4.32–4.20 (m, 2H), 3.99–3.95 (m, 1H), 3.51–3.45 (m, 1H), 2.31–2.29 (m, 1H), 2.05–1.92 (m, 3H), 1.62–1.52 (m, 2H), 1.28 (s, 9H), 1.01 (s, 9H). LCMS (M+H): 568.3.
Sources & evidence
- ORD record
- ord-23ef6d3f27d54987aaf9449ab888a579
- Source dataset
- uspto-grants-2006_12
- Patent number
- US07144899B2
Reaction notes
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