1-(2-Hydroxyethyl)piperazine → 1-Cyclohexyl-3-{3,5-dichloro-4'-[4-(2-hydroxy-ethyl)-piperazine-1-carbonyl]-biphenyl-4-ylmethyl}-pyrrolidin-2-one hydrochloride salt

HRID 416007ノート

反応式

HRID 416007 の反応式
[Cl:1][C:2]1[CH:3]=[C:4](OS(C(F)(F)F)(=O)=O)[CH:5]=[C:6]([Cl:21])[C:7]=1[CH2:8][CH:9]1[CH2:13][CH2:12][N:11]([CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]2)[C:10]1=[O:20].B([C:32]1[CH:37]=[CH:36][C:35]([C:38](Cl)=[O:39])=[CH:34][CH:33]=1)=O.[N:41]1([CH2:47][CH2:48][OH:49])[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]1.C(=O)([O-])[O-].[Na+].[Na+].[OH-].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(COC)OC>[ClH:1].[CH:14]1([N:11]2[CH2:12][CH2:13][CH:9]([CH2:8][C:7]3[C:2]([Cl:1])=[CH:3][C:4]([C:32]4[CH:37]=[CH:36][C:35]([C:38]([N:44]5[CH2:45][CH2:46][N:41]([CH2:47][CH2:48][OH:49])[CH2:42][CH2:43]5)=[O:39])=[CH:34][CH:33]=4)=[CH:5][C:6]=3[Cl:21])[C:10]2=[O:20])[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1

参加物

8

反応物 5

HCID 76771-(2-Hydroxyethyl)piperazineHCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 27733384-(Oxoboranyl)benzoyl chlorideHCID 592994213,5-Dichloro-4-((1-cyclohexyl-2-oxopyrrolidin-3-yl)methyl)phenyl trifluoromethanesulfonate

生成物 1

HCID 666218421-Cyclohexyl-3-{3,5-dichloro-4'-[4-(2-hydroxy-ethyl)-piperazine-1-carbonyl]-biphenyl-4-ylmethyl}-pyrrolidin-2-one hydrochloride salt収率 74%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
80 °C

実験手順

Combine Preparation 10 (trifluoro-methanesulfonic acid 3,5-dichloro-4-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-phenyl ester) (250 mg, 0.53 mmol), 4-chlorocarbonylphenylboronic anhydride (263 mg, 0.53 mmol) and Pd(PPh3)4 (61 mg, 0.053 mmol) and purge with nitrogen. Add 2-(piperazin-1-yl)ethanol (0.32 mL, 2.6 mmol) followed quickly by dimethoxyethane (5 mL) and 2M sodium carbonate (1 mL) and heat to 80° C. for 1 hour. Cool to room temperature and pour into 1N sodium hydroxide. Extract with ethyl acetate and wash the organic layer twice with water, followed by brine. Dry over sodium sulfate and concentrate in vacuo. Purify on SCX column (load and wash with methanol, elute with 2M ammonia in methanol). Dissolve resultant oil in methylene chloride. Add 2M hydrochloric acid in ether (1 mL) and concentrate under vacuum. Re-dissolve in small amount of methylene chloride and add dropwise to vigorously stirred ether. Filter precipitate and dry in vacuum oven to afford 231 mg (74%) of the title compound: MS (m/z): 558 (M+).

後処理

  1. custompurge with nitrogen
  2. temperatureCool to room temperature
  3. extractionExtract with ethyl acetate
  4. washwash the organic layer twice with water
  5. dry with materialDry over sodium sulfate
  6. concentrationconcentrate in vacuo
  7. customPurify on SCX column (load and wash with methanol, elute with 2M ammonia in methanol)
  8. dissolutionDissolve resultant oil in methylene chloride
  9. additionAdd 2M hydrochloric acid in ether (1 mL)
  10. concentrationconcentrate under vacuum
  11. additionRe-dissolve in small amount of methylene chloride and add dropwise to vigorously stirred ether
  12. filtrationFilter precipitate
  13. customdry in vacuum oven

出典と根拠

ORDレコード
ord-273fdd49580746f498895554e4bc5bf1
出典データセット
uspto-grants-2012_01
特許番号
US08088776B2

反応ノート

読み込み中…