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1,2-Dichloroethane → 1-(tert-Butoxycarbonyl)-D-prolyl-N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-L-prolinamide

HRID 857762
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HRID 857762 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:15][CH2:14][CH2:13][C@@H:9]1[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:16][C:17]1[CH:18]=[CH:19][C:20]([N:32]2[CH:36]=[N:35][N:34]=[N:33]2)=[C:21]([CH:31]=1)[CH2:22][NH:23][C:24](=[O:30])[C@@H:25]1[CH2:29][CH2:28][CH2:27][NH:26]1.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:15][CH2:14][CH2:13][C@@H:9]1[C:10]([N:26]1[CH2:27][CH2:28][CH2:29][C@H:25]1[C:24]([NH:23][CH2:22][C:21]1[CH:31]=[C:17]([Cl:16])[CH:18]=[CH:19][C:20]=1[N:32]1[CH:36]=[N:35][N:34]=[N:33]1)=[O:30])=[O:12])=[O:7])([CH3:2])([CH3:3])[CH3:4]
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참가 물질

6

반응물 4

HCID 111,2-DichloroethaneHCID 181649HOAtHCID 688022(2R)-1-[(tert-butoxy)carbonyl]pyrrolidine-2-carboxylic acidHCID 69655818N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-L-prolinamide

생성물 1

HCID 696564921-(tert-Butoxycarbonyl)-D-prolyl-N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-L-prolinamide

시약·촉매·용매 1

HCID 6228
Dimethylformamide
용매

실험 절차

The title compound was prepared from 1-(tert-butoxycarbonyl)-D-proline (49 mg, 0.23 mmol), N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-L-prolinamide (Example 26, Step B, 70 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 (500 μl) essentially according to the procedure described in Example 26, Step C. Preparative reverse phase HPLC [gradient elution with 95:5 water (+0.1% TFA)/CH3CN (+0.1% TFA) to 5:95 water (+0.1% TFA)/CH3CN (+0.1% TFA)] afforded the title compound as a clear oil. 1H NMR (400 MHz, CDCl3): δ 9.17 (s, 1 H), 8.11 (br s, 1 H), 7.54 (d, J=2.0 Hz, 1 H), 7.40 (dd, J=2.0, 8.4 Hz, 1 H), 7.23 (d, J=8.4 Hz, 1 H), 4.69–4.66 (m, 1 H), 4.43–4.39 (m, 1 H), 4.18–4.16 (m, 2 H), 4.04–3.99 (m, 1 H), 3.55–3.48 (m, 3 H), 2.27–1.88 (m, 8 H), 1.30 (s, 9 H). LCMS (M+H): 504.3.

후처리

  1. washPreparative reverse phase HPLC [gradient elution with 95:5 water (+0.1% TFA)/CH3CN (+0.1% TFA) to 5:95 water (+0.1% TFA)/CH3CN (+0.1% TFA)]

출처 및 근거

ORD 기록
ord-de57a734ca1144cbb684ffb19c327cf9
출처 데이터셋
uspto-grants-2006_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07144899B2

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