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

HRID 857781노트

반응식

HRID 857781 반응식
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]

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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.

출처 및 근거

ORD 기록
ord-23ef6d3f27d54987aaf9449ab888a579
출처 데이터셋
uspto-grants-2006_12
특허 번호
US07144899B2

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