Cesium carbonate → HCID 10133843, compound

HRID 2184009Notes

Reaction equation

HRID 2184009 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].CC1(C)COB([C:29]2[CH:30]=[N:31][CH:32]=[C:33]([CH3:35])[CH:34]=2)OC1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.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: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:29]1[CH:30]=[N:31][CH:32]=[C:33]([CH3:35])[CH:34]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 22473579HCID 22473579, compoundHCID 69708751HCID 69708751, compound

Product 1

HCID 10133843HCID 10133843, compoundYield 35%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

To a mixture of 3-(3-bromo-4-fluorophenyl)-7-trifluoromethylimidazo[1,2-α]pyrimidine (150 mg, 0.42 mmol) and 3-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)-5-methylpyridine in 1,4-dioxane (5 ml) was added a solution of caesium carbonate (340 mg, 1.04 mmol) in water (0.5 ml). The reaction was degassed with nitrogen and tetrakis(triphenylphosphine)palladium(0) (48 mg, 0.04 mmol) was added and the mixture heated at 70° C. for 1 h. The solvent was evaporated in vacuo and the residue was partitioned between dichloromethane and water. The aqueous phase was re-extracted with dichloromethane and the combined organic layers dried over anhydrous magnesium sulphate, filtered and evaporated. The residue was purified using a short silica gel column eluting with 2% diethyl ether in dichloromethane followed by 15% diethyl ether in dichloromethane to give a yellow solid. This was purified further by loading as a solution in methanol onto a cartridge of strong cation-exchange resin, eluting with methanol then with 2M ammonia in methanol. The basic fractions were concentrated in vacuo to give a dark cream solid. The solid was triturated with diethyl ether to give 3-[4-fluoro-3-(5-methylpyridin-3-yl)phenyl]-7-trifluoromethylimidazo[1,2-α]pyrimidine as a cream solid (55 mg, 35%): δH (360 MHz, d6-DMSO) 2.39 (3H, s), 7.51 (1H, d, J 7), 7.60 (1H, dd, J 11 and 9), 7.85 (1H, ddd, J 9, 5 and 2), 7.91-7.94 (1H, m), 8.00 (1H, dd, J 7 and 2), 8.33 (1H, s), 8.49 (2H, d, J 2), 8.68-8.71 (1H, m), 9.36 (1H, d, J 7); m/z (ES+) 373 (M++H).

Workup

  1. additionwas added
  2. customThe solvent was evaporated in vacuo
  3. customthe residue was partitioned between dichloromethane and water
  4. extractionThe aqueous phase was re-extracted with dichloromethane
  5. dry with materialthe combined organic layers dried over anhydrous magnesium sulphate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified
  9. washeluting with 2% diethyl ether in dichloromethane
  10. customto give a yellow solid
  11. customThis was purified further by loading as a solution in methanol onto a cartridge of strong cation-exchange resin
  12. washeluting with methanol
  13. concentrationThe basic fractions were concentrated in vacuo
  14. customto give a dark cream solid
  15. customThe solid was triturated with diethyl ether

Sources & evidence

ORD record
ord-7b4c4081994b46bfa8e084a5695252ab
Source dataset
uspto-grants-2005_05
Patent number
US06900215B2

Reaction notes

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