POTASSIUM DIPHOSPHATE → 4-(2-aminophenyl)-5-(3-benzenesulfonylpropyl)-1-butyl-1H-pyrazole-3-carbonitrile

HRID 1360551

反应方程式

HRID 1360551 反应方程式
Cl.[NH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1B(O)O.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[C:20]1([S:26]([CH2:29][CH2:30][CH2:31][C:32]2[N:36]([CH2:37][CH2:38][CH2:39][CH3:40])[N:35]=[C:34]([C:41]#[N:42])[C:33]=2Br)(=[O:28])=[O:27])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C1(C)C=CC=CC=1.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:33]1[C:34]([C:41]#[N:42])=[N:35][N:36]([CH2:37][CH2:38][CH2:39][CH3:40])[C:32]=1[CH2:31][CH2:30][CH2:29][S:26]([C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)(=[O:28])=[O:27]

参与物

7

反应物 3

HCID 62657POTASSIUM DIPHOSPHATEHCID 164270902-氨基苯硼酸盐酸盐HCID 669585995-(3-benzenesulfonylpropyl)4-bromo-1-butyl-1H-pyrazole-3-carbonitrile

产物 1

HCID 669588264-(2-aminophenyl)-5-(3-benzenesulfonylpropyl)-1-butyl-1H-pyrazole-3-carbonitrile收率 100.1%

试剂、催化剂与溶剂 3

HCID 9811564三(二亚苄基丙酮)二钯催化剂HCID 1140甲苯溶剂HCID 8857乙酸乙酯溶剂

反应条件

温度
110 °C

实验过程

2-Aminophenyl boronic acid hydrochloride (693 mg, 4.00 mmol) and potassium phosphate tribasic (2.12 g, 10.0 mmol) were added sequentially to a solution of 5-(3-benzenesulfonylpropyl)-4-bromo-1-butyl-1H-pyrazole-3-carbonitrile (550 mg, 1.30 mmol) in 15 mL of toluene in a pressure tube. Nitrogen was bubbled through the resultant slurry for 15 minutes. Tris(dibenzylideneacetone)dipalladium(0) (104 mg, 0.10 mmol), bis[(2-diphenylphosphino)phenyl]ether (65 mg, 0.12 mmol), and 4 angstrom molecular sieves were then added to the reaction mixture. The pressure tube was sealed and heated in a 110° C. oil bath. After 20 hours, the reaction mixture was cooled to ambient temperature, diluted with ethyl acetate and filtered through CELITE filter aid. The filtrate was diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate. The aqueous layer was extracted with additional ethyl acetate and the combined organic layers were washed with brine, dried over magnesium sulfate, filtered, and concentrated to an orange oil. Purification via flash column chromatography on silica gel (eluting with hexane:ethyl acetate in a gradient from 2:1 to 2:3) afforded 550 mg of 4-(2-aminophenyl)-5-(3-benzenesulfonylpropyl)-1-butyl-1H-pyrazole-3-carbonitrile as a thick pale yellow oil.

后处理

  1. customNitrogen was bubbled through the resultant slurry for 15 minutes
  2. customThe pressure tube was sealed
  3. temperaturethe reaction mixture was cooled to ambient temperature
  4. filtrationfiltered through CELITE
  5. filtrationfilter aid
  6. additionThe filtrate was diluted with ethyl acetate
  7. washwashed with saturated aqueous sodium bicarbonate
  8. extractionThe aqueous layer was extracted with additional ethyl acetate
  9. washthe combined organic layers were washed with brine
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated to an orange oil
  13. customPurification via flash column chromatography on silica gel (
  14. washeluting with hexane

来源与证据

ORD记录
ord-f9703a39462f40ecb80f2b571ec46514
来源数据集
uspto-grants-2011_02
专利号
US07879849B2

关联笔记

加载中…