1,2-Dichloroethane → N-(tert-butoxycarbonyl)-4-methyl-D-leucyl-N-[2-(1H-tetraazol-1-yl)-5-(trifluoromethyl)benzyl]-L-prolinamide

HRID 857781Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 857781
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]

Komponenten

8

Edukt 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 7021114(R)-2-((tert-Butoxycarbonyl)amino)-4,4-dimethylpentanoic acidHCID 69655976N-[2-(1H-tetraazol-1-yl)-5-(trifluoromethyl)benzyl]-L-prolinamide hydrochloride

Produkt 1

HCID 69656098N-(tert-butoxycarbonyl)-4-methyl-D-leucyl-N-[2-(1H-tetraazol-1-yl)-5-(trifluoromethyl)benzyl]-L-prolinamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

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.

Quellen und Nachweise

ORD-Eintrag
ord-23ef6d3f27d54987aaf9449ab888a579
Quelldatensatz
uspto-grants-2006_12
Patentnummer
US07144899B2

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