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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
ノート
印刷プレビュー

反応式

HRID 446982 の反応式
[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]
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 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

生成物 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
収率 60%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

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)+.

後処理

  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)

出典と根拠

ORDレコード
ord-8f8d63b448d142ff9ce62e85170eebac
出典データセット
uspto-grants-2013_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08481495B2

反応ノート

読み込み中…

このページの内容参加物実験手順後処理出典と根拠反応ノート