1,2-Dichloroethane → 4-methyl-D-leucyl-N-[5-chloro-2-(1H-1,2,4-triazol-1-yl)benzyl]-L-prolinamide

HRID 857747Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 857747
C(OC([NH:8][C@@H:9]([C:15]([OH:17])=O)[CH2:10][C:11]([CH3:14])([CH3:13])[CH3:12])=O)(C)(C)C.[Cl:18][C:19]1[CH:20]=[CH:21][C:22]([N:34]2[CH:38]=[N:37][CH:36]=[N:35]2)=[C:23]([CH:33]=1)[CH2:24][NH:25][C:26](=[O:32])[C@@H:27]1[CH2:31][CH2:30][CH2:29][NH:28]1.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1>CN(C=O)C.C(O)(C(F)(F)F)=O.C(Cl)Cl>[CH3:14][C:11]([CH3:12])([CH3:13])[CH2:10][C@H:9]([C:15]([N:28]1[CH2:29][CH2:30][CH2:31][C@H:27]1[C:26]([NH:25][CH2:24][C:23]1[CH:33]=[C:19]([Cl:18])[CH:20]=[CH:21][C:22]=1[N:34]1[CH:38]=[N:37][CH:36]=[N:35]1)=[O:32])=[O:17])[NH2:8]

Komponenten

7

Edukt 4

HCID 111,2-DichloroethaneHCID 181649HOAtHCID 7021114(R)-2-((tert-Butoxycarbonyl)amino)-4,4-dimethylpentanoic acidHCID 69656007N-[5-chloro-2-(1H-1,2,4-triazol-1-yl)benzyl]-L-prolinamide

Produkt 1

HCID 587601784-methyl-D-leucyl-N-[5-chloro-2-(1H-1,2,4-triazol-1-yl)benzyl]-L-prolinamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 21863450Trifluoroacetic acid methylene chlorideLösungsmittel

Versuchsvorschrift

The title compound was prepared from N-(tert-butoxycarbonyl)-4-methyl-D-leucine (32 mg, 0.13 mmol), N-[5-chloro-2-(1H-1,2,4-triazol-1-yl)benzyl]-L-prolinamide (Example 27, Step B, 50 mg, 0.21 mmol, 1.0 equiv), EDC (38 mg, 0.20 mmol, 1.5 equiv) and HOAt (9 mg, 0.07 mmol, 0.5 equiv) in DMF (1 mL) followed by deprotection in TFA-CH2Cl2 essentially according to the procedure described in Example 27, Step C. Purification by reverse phase chromatography [95:5 water (+0.1% TFA)/CH3CN (+0.1% TFA) to 50:50 water (+0.1% TFA)/CH3CN (+0.1% TFA)] followed by lyophilization of the fractions afforded the title compound as a white powder. 1H NMR (400 MHz, CDCl3): δ 8.81 (s, 1 H), 8.35 (br s, 2 H), 8.23 (s, 1 H), 8.09 (t, J=5.6Hz, 1 H), 7.50 (d, J=2.0 Hz, 1 H), 7.35 (dd, J=2.0, 8.4 Hz, 1 H), 7.24 (d, J=8.4 Hz, 1 H), 4.41–4.38 (m, 1 H), 4.29 (dd, J=5.6, 15.6 Hz, 1 H), 4.20–4.12 (m, 2 H), 3.87–3.83 (m, 1 H), 3.50–3.45 (m, 1 H), 2.12–2.02 (m, 3 H), 1.85–1.72 (m, 3 H), 0.96 (s, 9 H). HRMS (APCI) M+H: calculated for (C21H29N6O2Cl)+ 433.2113, found 433.2104.

Aufarbeitung

  1. customPurification by reverse phase chromatography [95:5 water (+0.1% TFA)/CH3CN (+0.1% TFA) to 50:50 water (+0.1% TFA)/CH3CN (+0.1% TFA)]

Quellen und Nachweise

ORD-Eintrag
ord-887e5bdb1d0640088e2c84cf7b814087
Quelldatensatz
uspto-grants-2006_12
Patentnummer
US07144899B2

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