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Ethanamine, 2,2,2-trifluoro- → (2R)-2-[(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutyl-2,5-dioxopiperazin-1-yl]-2-(4-fluorophenyl)-N-(2,2,2-trifluoroethyl)ethanamide

HRID 45607
ノート
印刷プレビュー

反応式

HRID 45607 の反応式
C(O[C:6]([NH:8][C@H:9]([CH:33]1[CH2:41][C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH2:34]1)[C:10]([N:12]([C@H:22]([C:26]1[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=1)[C:23](O)=[O:24])[C@@H:13](C(OC)=O)[CH2:14][CH:15]([CH3:17])[CH3:16])=[O:11])=[O:7])(C)(C)C.C(N(C(C)C)CC)(C)C.[F:51][C:52]([F:56])([F:55])[CH2:53][NH2:54]>CN(C)C=O>[CH2:41]1[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH2:34][CH:33]1[C@H:9]1[NH:8][C:6](=[O:7])[C@@H:13]([CH2:14][CH:15]([CH3:17])[CH3:16])[N:12]([C@H:22]([C:26]2[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=2)[C:23]([NH:54][CH2:53][C:52]([F:56])([F:55])[F:51])=[O:24])[C:10]1=[O:11]
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 9773Ethanamine, 2,2,2-trifluoro-HCID 81531DiisopropylethylamineHCID 57439045(2R)-{[(2R)-2-[(tert-butoxycarbonyl)amino]-2-(2,3-dihydro-1H-inden-2-yl)ethanoyl][(1R)-1-(methoxycarbonyl)-3-methylbutyl]amino}(4-fluorophenyl)ethanoic acid

生成物 1

HCID 11375822(2R)-2-[(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutyl-2,5-dioxopiperazin-1-yl]-2-(4-fluorophenyl)-N-(2,2,2-trifluoroethyl)ethanamide

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A solution of (2R)-{[(2R)-2-[(tert-butoxycarbonyl)amino]-2-(2,3-dihydro-1H-inden-2-yl)ethanoyl][(1R)-1-(methoxycarbonyl)-3-methylbutyl]amino}(4-fluorophenyl)ethanoic acid (73 mg) in N,N-dimethylformamide (2 ml) was sequentially treated with diisopropylethylamine (51 μl), phosphorusI (1-hydroxy-1H-benzotriazolato-O)tri-1-pyrrolidinyl-(T-4)-hexafluorophosphate (80 mg) and then after 2 minutes, 2,2,2-trifluoroethylamine (25 μl). This reaction mixture was stirred for 2 hours before being partitioned between 2M aqueous hydrochloric acid and ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate solution and brine before being dried over magnesium sulphate and evaporated in vacuo. The residue was dissolved in 4M hydrogen chloride in dioxane and stirred for 7 hours at room temperature. The reagent was removed in vacuo and the residue partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution. The separated organic fraction was washed with brine before being dried over magnesium sulphate and evaporated in vacuo. The crude material was purified by column chromatography (silica) eluting with methanol:dichloromethane (1% to 3%) to furnish ((2R)-2-[(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutyl-2,5-dioxopiperazin-1-yl]-2-(4-fluorophenyl)-N-(2,2,2-trifluoroethyl)ethanamide (10 mg)

後処理

  1. custombefore being partitioned between 2M aqueous hydrochloric acid and ethyl acetate
  2. washThe organic layer was washed with saturated aqueous sodium bicarbonate solution and brine
  3. dry with materialbefore being dried over magnesium sulphate
  4. customevaporated in vacuo
  5. dissolutionThe residue was dissolved in 4M hydrogen chloride in dioxane
  6. stirringstirred for 7 hours at room temperature
  7. customThe reagent was removed in vacuo
  8. customthe residue partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution
  9. washThe separated organic fraction was washed with brine
  10. dry with materialbefore being dried over magnesium sulphate
  11. customevaporated in vacuo
  12. customThe crude material was purified by column chromatography (silica)
  13. washeluting with methanol

出典と根拠

ORDレコード
ord-d2c49389091e4e5e99cd75694aff8b82
出典データセット
uspto-grants-2013_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08541579B2

反応ノート

読み込み中…

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