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

HRID 857781ノート

反応式

HRID 857781 の反応式
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]

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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.

出典と根拠

ORDレコード
ord-23ef6d3f27d54987aaf9449ab888a579
出典データセット
uspto-grants-2006_12
特許番号
US07144899B2

反応ノート

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