Cesium carbonate → HCID 9902790, compound

HRID 1796027Notes

Reaction equation

HRID 1796027 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:7]2[N:11]3[CH:12]=[CH:13][C:14]([C:16]([F:19])([F:18])[F:17])=[N:15][C:10]3=[N:9][CH:8]=2)[S:5][CH:6]=1.B1([C:26]2[CH:31]=[CH:30][CH:29]=[N:28][CH:27]=2)OCCCO1.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>[N:28]1[CH:29]=[CH:30][CH:31]=[C:26]([C:2]2[CH:3]=[C:4]([C:7]3[N:11]4[CH:12]=[CH:13][C:14]([C:16]([F:19])([F:18])[F:17])=[N:15][C:10]4=[N:9][CH:8]=3)[S:5][CH:6]=2)[CH:27]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 41980053-(1,3,2-Dioxaborinan-2-yl)pyridineHCID 69559414HCID 69559414, compound

Product 1

HCID 9902790HCID 9902790, compoundYield 80%

Reagents, catalysts & solvents 3

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

Procedure

A mixture of 3-(4-bromothien-2-yl)-7-trifluoromethylimidazo[1,2-α]pyrimidine (104 mg, 0.3 mmol), pyridine-3-boronic acid-1,3-propanediol cyclic ester (73 g, 0.45 mmol), cesium carbonate (0.29 g, 0.9 mmol) and tetrakis(triphenylphosphine)palladium(0) (34 mg, 0.03 mmol) in 1,4-dioxane (5 ml) and H2O (0.5 ml) were degassed with a stream of N2 for 10 min. The reaction mixture was then heated at reflux for 1 h. The mixture was concentrated under reduced pressure to remove the organic solvents and H2O (20 ml) was added. The organics were extracted with dichloromethane (2×50 ml) and concentrated under reduced pressure while dry loading onto silica. The resulting crude residue was purified by column chromatography on silica using 70% EtOAc in hexanes containing 1% Et3N and 1% MeOH as the eluent. The resulting material was taken up in MeOH and was poured onto a strong cation exchange cartridge and eluted with methanol. The product was then eluted with 2.0M NH3 in MeOH and evaporated to give 3-[4-(pyridin-3-yl)thien-2-yl]-7-trifluoromethylimidazo[1,2-α]pyrimidine (83 mg, 80%): δH (400 MHz, d6-DMSO) 7.46-7.53 (1H, m), 7.60 (1H, d, J 7.1), 8.18 (1H, d, J 1.5), 8.22-8.30 (1H, m), 8.26 (1H, d, J 1.5), 8.42 (1H, s), 8.56-8.60 (1H, m), 9.10 (1H, s), 10.20 (1H, d, J 7.1); m/z (ES+) 346 (M+).

Workup

  1. customwere degassed with a stream of N2 for 10 min
  2. temperatureThe reaction mixture was then heated
  3. temperatureat reflux for 1 h
  4. concentrationThe mixture was concentrated under reduced pressure
  5. customto remove the organic solvents and H2O (20 ml)
  6. additionwas added
  7. extractionThe organics were extracted with dichloromethane (2×50 ml)
  8. concentrationconcentrated under reduced pressure
  9. customwhile dry loading onto silica
  10. customThe resulting crude residue was purified by column chromatography on silica using 70% EtOAc in hexanes containing 1% Et3N and 1% MeOH as the eluent
  11. additionwas poured onto a strong cation exchange cartridge
  12. washeluted with methanol
  13. washThe product was then eluted with 2.0M NH3 in MeOH
  14. customevaporated

Sources & evidence

ORD record
ord-fa8d0a71e63d4c4fbbd1258b56dc5344
Source dataset
uspto-grants-2006_04
Patent number
US07030128B2

Reaction notes

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