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1,2-Dichloroethane → 3-methyl-D-valyl-N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-L-prolinamide

HRID 857746
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HRID 857746 반응식
C(OC([NH:8][C@@H:9]([C:14]([OH:16])=O)[C:10]([CH3:13])([CH3:12])[CH3:11])=O)(C)(C)C.[Cl:17][C:18]1[CH:19]=[CH:20][C:21]([N:33]2[CH:37]=[N:36][N:35]=[N:34]2)=[C:22]([CH:32]=1)[CH2:23][NH:24][C:25](=[O:31])[C@@H:26]1[CH2:30][CH2:29][CH2:28][NH:27]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>[CH3:13][C:10]([CH3:11])([CH3:12])[C@H:9]([C:14]([N:27]1[CH2:28][CH2:29][CH2:30][C@H:26]1[C:25]([NH:24][CH2:23][C:22]1[CH:32]=[C:18]([Cl:17])[CH:19]=[CH:20][C:21]=1[N:33]1[CH:37]=[N:36][N:35]=[N:34]1)=[O:31])=[O:16])[NH2:8]
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참가 물질

7

반응물 4

HCID 111,2-DichloroethaneHCID 181649HOAtHCID 7005057(2R)-2-{[(tert-butoxy)carbonyl]amino}-3,3-dimethylbutanoic acidHCID 69655818N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-L-prolinamide

생성물 1

HCID 587601623-methyl-D-valyl-N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-L-prolinamide

시약·촉매·용매 2

HCID 6228
Dimethylformamide
용매
HCID 21863450Trifluoroacetic acid methylene chloride용매

실험 절차

The title compound was prepared from N-(tert-butoxycarbonyl)-3-methyl-D-valine (53 mg, 0.23 mmol), N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-L-prolinamide (Example 26, Step B, 87 mg, 0.23 mmol, 1.0 equiv), EDC (66 mg, 0.34 mmol, 1.5 equiv) and HOAt (16 mg, 0.11 mmol, 0.5 equiv) in DMF (1 mL) followed by deprotection in TFA-CH2Cl2 essentially according to the procedure described in Example 26, 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 (300 MHz, CDCl3): δ 9.22 (s, 1 H), 8.32–8.29 (m, 3 H), 7.85 (d, J=1.8 Hz, 1 H), 7.43 (dd, J=2.1, 8.4 Hz, 1 H), 7.15 (d, J=8.4 Hz, 1 H), 4.45 (app d, J=8.1 Hz, 1 H), 4.35–4.27 (m, 2 H), 3.95–3.79 (m, 2 H), 3.62–3.56 (m, 1 H), 2.31–2.25 (m, 1 H), 2.10–1.87 (m, 3 H), 1.18 (s, 9 H). HRMS (APCI) M+H: calculated for (C19H26N7O2Cl)+ 420.1910, found 420.1915.

후처리

  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)]

출처 및 근거

ORD 기록
ord-86c64e5a477f457ba7143c83d7895169
출처 데이터셋
uspto-grants-2006_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07144899B2

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