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

HRID 323243

반응식

HRID 323243 반응식
[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].I.[NH:34]1[C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=2[N:36]=[C:35]1[NH:43][CH:44]1[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]1.C(N(CC)C(C)C)(C)C.N>C(OCC)(=O)C.ClCCl.CO.C(OCC)(=O)C.C(#N)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:47]2[CH2:46][CH2:45][CH:44]([NH:43][C:35]3[NH:34][C:38]4[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=4[N:36]=3)[CH2:49][CH2:48]2)([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:9]1)=[O:7]

참가 물질

9

반응물 4

HCID 222AmmoniaHCID 81531DiisopropylethylamineHCID 184646303,4,5-Trimethoxybenzoyl-3-phenyl-3-(2-methanesulfonyloxyethyl)pyrrolidineHCID 86754231(1H-benzimidazol-2-yl)(piperidin-4-yl)amine hydriodic acid

생성물 1

HCID 99382691-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-phenylpyrrolidine

시약·촉매·용매 4

HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매HCID 21584119Ethylacetate methanol용매

실험 절차

Combine 1-(3,4,5-trimethoxybenzoyl)-3-phenyl-3-(2-methanesulfonyloxyethyl)pyrrolidine (prepared from (−)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine (R,R)-di-p-anisoyltartaric acid salt) (2.51 g, 5.4 mmol), (1H-benzimidazol-2-yl)(piperidin-4-yl)amine hydriodic acid salt (3.07 g, 6.5 mmol), N,N-diisopropylethylamine (4.8 mL, 27.6 mmol), and acetonitrile (70 mL). Heat to reflux. After 18 hours, cool to ambient temperature, dilute the reaction mixture with ethyl acetate, and extract with water and brine. Separate the organic layer, dry over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with 305 methanol/ethyl acetate containing concentrated aqueous ammonia 22 mL/3L. Evaporate the product containing fractions to give a residue. Combine the residue and dichloromethane, filter and evaporate in vacuo to give the title compound: Rf=0.17 (silica gel, 30% methanol/ethyl acetate).

후처리

  1. temperatureHeat to reflux
  2. extractionextract with water and brine
  3. customSeparate the organic layer
  4. dry with materialdry over Na2SO4
  5. filtrationfilter
  6. customevaporate in vacuo
  7. customto give a residue
  8. customEvaporate the product
  9. additioncontaining fractions
  10. customto give a residue
  11. filtrationfilter
  12. customevaporate in vacuo

출처 및 근거

ORD 기록
ord-61019cd3e3e9455ea63690876bd55da5
출처 데이터셋
uspto-grants-2001_04
특허 번호
US06211199B1

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