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Water → 3-(4-Fluoro-phenyl)-6-[2-(4-fluoro-phenyl)-2H-pyrazol-3-yl]-imidazo[1,2-a]pyridine

HRID 629272
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HRID 629272 반응식
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)=[CH:9][N:10]=2)[CH:7]=1.[F:18][C:19]1[CH:24]=[CH:23][C:22]([N:25]2[C:29](B3OC(C)(C)C(C)(C)O3)=[CH:28][CH:27]=[N:26]2)=[CH:21][CH:20]=1.C([O-])([O-])=O.[Na+].[Na+].O>COCCOC.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>[F:17][C:14]1[CH:15]=[CH:16][C:11]([C:8]2[N:6]3[CH:7]=[C:2]([C:29]4[N:25]([C:22]5[CH:23]=[CH:24][C:19]([F:18])=[CH:20][CH:21]=5)[N:26]=[CH:27][CH:28]=4)[CH:3]=[CH:4][C:5]3=[N:10][CH:9]=2)=[CH:12][CH:13]=1
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참가 물질

7

반응물 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 901891376-Bromo-3-(4-fluorophenyl)-imidazo[1,2-a]pyridine2회HCID 901893681-(4-fluorophenyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole2회

생성물 1

HCID 760725243-(4-Fluoro-phenyl)-6-[2-(4-fluoro-phenyl)-2H-pyrazol-3-yl]-imidazo[1,2-a]pyridine수율 31.2%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 80711,2-Dimethoxyethane용매

실험 절차

To a mixture of 6-bromo-3-(4-fluorophenyl)-imidazo[1,2-a]pyridine (intermediate E) (100 mg, 344 μmol) and 1-(4-fluoro-phenyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (intermediate A) (119 mg, 412 μl) in 1,2-dimethoxyethane (2 ml), was added 1M Na2CO3 (859 μl, 859 μmol), and the reaction mixture was purged with argon for 10 min in an ultrasonic bath. Afterwards tetrakis(triphenylphosphine)palladium(0) (39.7 mg, 34.4 μmol) was added, and the stirred reaction mixture was heated under reflux conditions for 17 h. The reaction mixture was cooled to room temperature, poured into water (20 ml) and extracted with ethyl acetate (2×20 ml). The combined organic layers were washed with brine (20 ml), dried (MgSO4) and evaporated. The crude material (190 mg) was further purified by flash chromatography on silica gel (dichloromethane/MeOH, 0-20%) and trituration (diethyl ether) to yield the title compound as an off-white solid (40 mg, 31%), MS (ISP) m/z=373.4 [(M+H)+], mp 172° C.

후처리

  1. customthe reaction mixture was purged with argon for 10 min in an ultrasonic bath
  2. customthe stirred reaction mixture
  3. temperaturewas heated under reflux conditions for 17 h
  4. extractionextracted with ethyl acetate (2×20 ml)
  5. washThe combined organic layers were washed with brine (20 ml)
  6. dry with materialdried (MgSO4)
  7. customevaporated
  8. customThe crude material (190 mg) was further purified by flash chromatography on silica gel (dichloromethane/MeOH, 0-20%) and trituration (diethyl ether)

출처 및 근거

ORD 기록
ord-b92e13fb1ed246aab28d5c24368ac4fc
출처 데이터셋
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09315502B2

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