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

HRID 1660949노트

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HRID 1660949 반응식
[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]

참가 물질

9

반응물 3

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

생성물 1

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

시약·촉매·용매 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 702Ethanol용매HCID 962Water용매HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-6168c1083e834184a75fc31f4925010e
출처 데이터셋
uspto-grants-2011_10
특허 번호
US08030311B2

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