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

HRID 857747ノート

反応式

HRID 857747 の反応式
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]

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 21863450Trifluoroacetic acid methylene chloride溶媒

実験手順

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.

後処理

  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)]

出典と根拠

ORDレコード
ord-887e5bdb1d0640088e2c84cf7b814087
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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