Sodium Carbonate → N-(4'-Cyano-2-trifluoromethyl-biphen-4-yl)-2-(4-imidazo[4,5-b]pyridin-3-yl-phenyl)-acetamide

HRID 1660949ノート

反応式

HRID 1660949 の反応式
[C:1]([C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1)#[N:2].[N:12]1[C:20]2[C:15](=[N:16][CH:17]=[CH:18][CH:19]=2)[N:14]([C:21]2[CH:26]=[CH:25][C:24]([CH2:27][C:28]([NH:30][C:31]3[CH:36]=[CH:35][C:34](I)=[C:33]([C:38]([F:41])([F:40])[F:39])[CH:32]=3)=[O:29])=[CH:23][CH:22]=2)[CH:13]=1.C([O-])([O-])=O.[Na+].[Na+]>CCO.C1(C)C=CC=CC=1.CCOC(C)=O.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:34]2[C:33]([C:38]([F:39])([F:40])[F:41])=[CH:32][C:31]([NH:30][C:28](=[O:29])[CH2:27][C:24]3[CH:23]=[CH:22][C:21]([N:14]4[C:15]5=[N:16][CH:17]=[CH:18][CH:19]=[C:20]5[N:12]=[CH:13]4)=[CH:26][CH:25]=3)=[CH:36][CH:35]=2)=[CH:5][CH:4]=1)#[N:2]

参加物

9

反応物 3

HCID 10340Sodium CarbonateHCID 27343264-Cyanophenylboronic acidHCID 119935762-(4-imidazo[4,5-b]pyridin-3-yl-phenyl)-N-(4-iodo-3-trifluoromethyl-phenyl)-acetamide

生成物 1

HCID 11993577N-(4'-Cyano-2-trifluoromethyl-biphen-4-yl)-2-(4-imidazo[4,5-b]pyridin-3-yl-phenyl)-acetamide

試薬・触媒・溶媒 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 702Ethanol溶媒HCID 962Water溶媒HCID 1140Toluene溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A mixture of 4-cyanophenylboronic acid (62 mg, 0.42 mmol, 2 equiv) in EtOH (0.2 mL) is added dropwise to a mixture of 2-(4-imidazo[4,5-b]pyridin-3-yl-phenyl)-N-(4-iodo-3-trifluoromethyl-phenyl)-acetamide (Example 12) (110 mg, 0.21 mmol), PdCl2(dppf)2 (5 mg, 0.01 mmol, 0.03 equiv), Na2CO3 (2 M solution in H2O, 0.42 mL, 0.84 mmol, 4 equiv) in toluene (1 mL) at reflux. The reaction mixture is stirred at reflux for 1 h, allowed to cool to rt and diluted with EtOAc and H2O. The aqueous layer is separated and extracted twice with EtOAc. The combined organic phase is washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. Silica gel column chromatography purification (CH2Cl2/MeOH, 96:4) provides the title compound as a white solid: ES-MS: 495.9 [M-H]−; single peak at tR=4.68 min (System 1); Rf=0.15 (CH2Cl2/MeOH, 96:4).

後処理

  1. temperatureat reflux
  2. temperatureat reflux for 1 h
  3. customThe aqueous layer is separated
  4. extractionextracted twice with EtOAc
  5. washThe combined organic phase is washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customSilica gel column chromatography purification (CH2Cl2/MeOH, 96:4)

出典と根拠

ORDレコード
ord-6168c1083e834184a75fc31f4925010e
出典データセット
uspto-grants-2011_10
特許番号
US08030311B2

反応ノート

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