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

HRID 629272Notes

Reaction equation

HRID 629272 reaction equation
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

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 901891376-Bromo-3-(4-fluorophenyl)-imidazo[1,2-a]pyridine2×HCID 901893681-(4-fluorophenyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole2×

Product 1

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

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-b92e13fb1ed246aab28d5c24368ac4fc
Source dataset
uspto-grants-2016_04
Patent number
US09315502B2

Reaction notes

Loading…