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1,2-Dichloroethane → {1-Cyclohexyl-2-[4-cyclopropanecarbonyl-6-(1,2,3,4-tetrahydro-naphthalen-1-ylcarbamoyl)-hexahydro-pyrrolo[3,2-b]pyrrol-1-yl]-2-oxo-ethyl}-carbamic acid tert-butyl ester

HRID 446982
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HRID 446982 반응식
[C:1]([O:5][C:6]([NH:8][CH:9]([CH:28]1[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1)[C:10]([N:12]1[CH:19]2[CH:15]([N:16]([C:23]([CH:25]3[CH2:27][CH2:26]3)=[O:24])[CH2:17][CH:18]2[C:20]([OH:22])=O)[CH2:14][CH2:13]1)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:34](Cl)[CH2:35]Cl.[CH:38]1[CH:39]=[CH:40][C:41]2N(O)N=[N:44][C:42]=2[CH:43]=1.[CH3:48][CH2:49]N(C(C)C)C(C)C>C(Cl)Cl>[C:1]([O:5][C:6](=[O:7])[NH:8][CH:9]([CH:28]1[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33]1)[C:10]([N:12]1[CH2:13][CH2:14][CH:15]2[N:16]([C:23]([CH:25]3[CH2:27][CH2:26]3)=[O:24])[CH2:17][CH:18]([C:20](=[O:22])[NH:44][CH:42]3[C:41]4[C:40](=[CH:48][CH:49]=[CH:34][CH:35]=4)[CH2:39][CH2:38][CH2:43]3)[CH:19]12)=[O:11])([CH3:2])([CH3:4])[CH3:3]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

6

반응물 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 672806544-(2-tert-Butoxycarbonylamino-2-cyclohexyl-acetyl)-1-cyclopropanecarbonyl-octahydro-pyrrolo[3,2-b]pyrrole-3-carboxylic acid

생성물 1

HCID 67280896{1-Cyclohexyl-2-[4-cyclopropanecarbonyl-6-(1,2,3,4-tetrahydro-naphthalen-1-ylcarbamoyl)-hexahydro-pyrrolo[3,2-b]pyrrol-1-yl]-2-oxo-ethyl}-carbamic acid tert-butyl ester
수율 60%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

A solution of 45 (563 mg, 1.21 mmol) in DCM (15 mL) was cooled to 0° C. and treated with R-(−)-tetrahydronaphthylamine (0.17 mL, 1.21 mmol), EDC (279 mg, 1.46 mmol), HOBt (197 mg, 1.46 mmol) and DIPEA (0.66 mL, 3.76 mmol), respectively. After 18 h, the solution was diluted with DCM, washed successively with 1M HCl, saturated aqueous NaHCO3, and brine, dried over anhydrous Na2SO4, filtered and concentrated. Purification by reverse phase HPLC (2″ Dynamax® C18, 20-100% ACN in H2O with 0.1% HOAc over 30 min) afforded 46 (430 mg) as a white foam. 1H NMR (CDCl3, 300 MHz), ˜1:1 mixture of rotomers: δ8.36 (d, J=8.4 Hz, 0.25H), 8.09 (d, J=8.7 Hz, 0.25H), 7.35 (d, J=9 Hz, 0.5H), 7.28-7.20 (m, 0.5H), 7.18-7.05 (m, 3.5H), 6.52 (d, J=8.4 Hz, 0.25H) 5.25-5.02 (m, 2H), 4.91-4.84 (m, 0.5H), 4.72-4.44 (m, 2H), 4.33-4.19 (m, 1.5H), 4.05-3.93 (m, 1H), 3.67-3.58 (m, 0.5H), 3.49-3.31 (m 1H), 3.15-2.98 (m, 1H), 2.86-2.71 (m, 2H), 2.44-2.35 (m, 1H), 1.98-1.54 (m, 10H), 1.44 (s, 5.5H), 1.17-0.75 (m, 15H) ppm. Mass spectrum, m/z [593.8] (M+H)+.

후처리

  1. washwashed successively with 1M HCl, saturated aqueous NaHCO3, and brine
  2. dry with materialdried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by reverse phase HPLC (2″ Dynamax® C18, 20-100% ACN in H2O with 0.1% HOAc over 30 min)

출처 및 근거

ORD 기록
ord-8f8d63b448d142ff9ce62e85170eebac
출처 데이터셋
uspto-grants-2013_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08481495B2

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