Ethyl Acetate → 1-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1-(4-fluorobenzyl)-1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-phenylpyrrolidine

HRID 323211

反応式

HRID 323211 の反応式
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:26]=[C:27]([O:31][CH3:32])[C:28]=1[O:29][CH3:30])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([CH2:13][CH2:14]OS(C)(=O)=O)[CH2:9]1)=[O:7].[F:33][C:34]1[CH:56]=[CH:55][C:37]([CH2:38][N:39]2[C:43]3[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=3[N:41]=[C:40]2[NH:48][CH:49]2[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]2)=[CH:36][CH:35]=1.C(N(CC)C(C)C)(C)C.C(OCC)(=O)C>C(#N)C.CO.C(OCC)(=O)C>[CH3:32][O:31][C:27]1[CH:26]=[C:5]([CH:4]=[C:3]([O:2][CH3:1])[C:28]=1[O:29][CH3:30])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([CH2:13][CH2:14][N:52]2[CH2:53][CH2:54][CH:49]([NH:48][C:40]3[N:39]([CH2:38][C:37]4[CH:55]=[CH:56][C:34]([F:33])=[CH:35][CH:36]=4)[C:43]4[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=4[N:41]=3)[CH2:50][CH2:51]2)([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:9]1)=[O:7]

参加物

7

反応物 4

HCID 8857Ethyl Acetate2 回HCID 81531DiisopropylethylamineHCID 123618TecastemizoleHCID 184646303,4,5-Trimethoxybenzoyl-3-phenyl-3-(2-methanesulfonyloxyethyl)pyrrolidine

生成物 1

HCID 98748221-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1-(4-fluorobenzyl)-1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-phenylpyrrolidine

試薬・触媒・溶媒 2

HCID 6342Acetonitrile溶媒HCID 21584119Ethylacetate methanol溶媒

実験手順

Combine 1-(3,4,5-trimethoxybenzoyl)-3-phenyl-3-(2-methanesulfonyloxyethyl)pyrrolidine (0.42 g, 0.9 mmol) and (1(4-fluorobenzyl)-1H-benzimidazol-2-yl)(piperidin-4-yl)amine (0.49 g, 1.5 mmol), and N,N-diisopropylethylamine (0.40 mL, 2.3 mmol) in acetonitrile (12 mL). Heat to reflux. After 18 hours, pour the reaction mixture into ethyl acetate. Extract twice with water, saturated aqueous sodium bicarbonate solution, and aqueous sodium chloride solution. Dry the organic layer over Na2SO4, filter, and concentrate in vacuo to obtain a residue. Chromatograph the residue on a short column of silica gel eluting sequentially with ethyl acetate and then 25% methanol/ethyl acetate. Evaporate the product containing fractions and partition between dichloromethane and 1/1 brine/water. Dry the organic layer over Na2SO4, filter, and concentrate in vacuo to give the title compound: Rf=0.38 silica gel, 25% methanol/ethyl acetate).

後処理

  1. temperatureHeat to reflux
  2. extractionExtract twice with water, saturated aqueous sodium bicarbonate solution, and aqueous sodium chloride solution
  3. dry with materialDry the organic layer over Na2SO4
  4. filtrationfilter
  5. concentrationconcentrate in vacuo
  6. customto obtain a residue
  7. customEvaporate the product
  8. additioncontaining fractions
  9. custompartition between dichloromethane and 1/1 brine/water
  10. dry with materialDry the organic layer over Na2SO4
  11. filtrationfilter
  12. concentrationconcentrate in vacuo

出典と根拠

ORDレコード
ord-e2dc7ef66552441988bd284e10b849d5
出典データセット
uspto-grants-2001_04
特許番号
US06211199B1

関連ノート

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