2-(Tributylstannyl)pyridine → HCID 10269749, compound

HRID 2183924Notes

Reaction equation

HRID 2183924 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:9]2[N:13]3[CH:14]=[CH:15][C:16]([C:18]([F:21])([F:20])[F:19])=[N:17][C:12]3=[N:11][CH:10]=2)[CH:5]=[CH:6][C:7]=1[F:8].C([Sn](CCCC)(CCCC)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=1)CCC>CN(C)C=O.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[F:8][C:7]1[CH:6]=[CH:5][C:4]([C:9]2[N:13]3[CH:14]=[CH:15][C:16]([C:18]([F:21])([F:20])[F:19])=[N:17][C:12]3=[N:11][CH:10]=2)=[CH:3][C:2]=1[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=1

Participants

5

Reactant 2

HCID 6077842-(Tributylstannyl)pyridineHCID 69708751HCID 69708751, compound

Product 1

HCID 10269749HCID 10269749, compound

Reagents, catalysts & solvents 2

HCID 53485975CID 53485975CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 3-(3-bromo-4-fluorophenyl)-7-trifluoromethylimidazo[1,2-α]pyrimidine (0.190 g, 0.528 mmol) in N,N-dimethylformamide (5 ml) was added 2-tri-n-butylstannylpyridine (0.265 g) followed by dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (0.187 g). The mixture was heated at 100° C. for 9 h. The solvent was evaporated at reduced pressure and the residue chromatographed on silica gel eluting with 4% methanol in dichloromethane. The residue was then loaded onto a cartridge of strong cation-exchange resin. Elution with methanol gave non-basic impurities. Further elution with 2M ammonia in methanol gave crude product. Further purification by preparative thin-layer chromatography on silica gel using 4% methanol in dichloromethane as eluant and crystallisation of the residue from toluene/isohexane afforded 3-[4-fluoro-3-(pyridin-2-yl)phenyl]-7-trifluoromethylimidazo[1,2-α]pyrimidine as yellow needles: δH (400 MHz, DMSO) 7.46 (1H, m), 7.53 (1H, d, J 7), 7.61 (1H, dd, J 11 and 9), 7.86-7.91 (2H, m), 7.95-7.99 (1H, m), 8.24 (1H, dd, J 7 and 2), 8.30 (1H, s), 8.74-8.76 (1H, m), 9.27 (1H, d, J 7); m/z (ES+) 359 (M++H).

Workup

  1. customThe solvent was evaporated at reduced pressure
  2. customthe residue chromatographed on silica gel eluting with 4% methanol in dichloromethane
  3. washElution with methanol
  4. customgave non-basic impurities
  5. washFurther elution with 2M ammonia in methanol
  6. customgave crude product
  7. customFurther purification by preparative thin-layer chromatography on silica gel using 4% methanol in dichloromethane as eluant
  8. customcrystallisation of the residue from toluene/isohexane

Sources & evidence

ORD record
ord-6f791877148345cab2d1980a0f430dae
Source dataset
uspto-grants-2005_05
Patent number
US06900215B2

Reaction notes

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