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

HRID 857747노트

반응식

HRID 857747 반응식
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]

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 21863450Trifluoroacetic acid methylene chloride용매

실험 절차

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.

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-887e5bdb1d0640088e2c84cf7b814087
출처 데이터셋
uspto-grants-2006_12
특허 번호
US07144899B2

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