Diethyl Ether → 3-[2-(2,5-Dimethyl-pyrrol-1-yl)-4-trifluoromethyl-thiazol-5-yl]-7-(1-ethyl-propyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine

HRID 1660759Notes

Reaction equation

HRID 1660759 reaction equation
Br[C:2]1[S:6][C:5]([N:7]2[C:11]([CH3:12])=[CH:10][CH:9]=[C:8]2[CH3:13])=[N:4][C:3]=1[C:14]([F:17])([F:16])[F:15].C([Li])(C)(C)C.[CH2:23]([CH:25]([C:28]1[N:33]2[N:34]=[C:35]([CH3:38])[C:36](I)=[C:32]2[N:31]=[C:30]([CH3:39])[CH:29]=1)[CH2:26][CH3:27])[CH3:24].C(OCC)C>C1COCC1.[Cl-].[Zn+2].[Cl-].CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH3:13][C:8]1[N:7]([C:5]2[S:6][C:2]([C:36]3[C:35]([CH3:38])=[N:34][N:33]4[C:28]([CH:25]([CH2:23][CH3:24])[CH2:26][CH3:27])=[CH:29][C:30]([CH3:39])=[N:31][C:32]=34)=[C:3]([C:14]([F:17])([F:16])[F:15])[N:4]=2)[C:11]([CH3:12])=[CH:10][CH:9]=1

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 248985233-Iodo-2,5-dimethyl-7-(pentan-3-yl)pyrazolo[1,5-a]pyrimidineHCID 674291065-Bromo-2-(2,5-dimethyl-pyrrol-1-yl)-4-trifluoromethyl-thiazoleHCID 178418306HCID 178418306, compound

Product 1

HCID 594740583-[2-(2,5-Dimethyl-pyrrol-1-yl)-4-trifluoromethyl-thiazol-5-yl]-7-(1-ethyl-propyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidineYield 72.4%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418851HCID 178418851, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Cool a solution of 5-bromo-2-(2,5-dimethyl-pyrrol-1-yl)-4-trifluoromethyl-thiazole (2.2 g, 6.6 mmol) in THF (25 mL) in a dry ice bath. Add t-butyl lithium (1.7 M in pentane, 8.5 mL, 14.5 mmol) dropwise. Stir for 45 min and then add zinc chloride (0.5 M in THF, 14.6 mL, 7.3 mmol) dropwise. Stir 5 min and remove the cooling bath. Stir 30 min and then add 7-(1-ethyl-propyl)-3-iodo-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine (1.5 g, 4.4 mmol) and bis(tri-t-butylphosphine)palladium (0) (450 mg, 0.9 mmol). Reflux for 24 h. Cool the reaction, pour the mixture into diethyl ether, and wash with water (2×). Extract the combined water layers with diethyl ether. Dry the combined organic portions over sodium sulfate, filter, and concentrate to dryness under vacuum. Purify the resulting residue by silica gel chromatography (75-100% CH2Cl2 in hexanes) to give the title compound (1.47 g, 72%). HR-ToF-MS m/z calcd for C23H26F3N5S+H+: 462.1939, found: 462.1915.

Workup

  1. stirringStir 5 min
  2. customremove the cooling bath
  3. stirringStir 30 min
  4. temperatureReflux for 24 h
  5. temperatureCool
  6. customthe reaction
  7. washwash with water (2×)
  8. extractionExtract the combined water layers with diethyl ether
  9. dry with materialDry the combined organic portions over sodium sulfate
  10. filtrationfilter
  11. concentrationconcentrate to dryness under vacuum
  12. customPurify the resulting residue by silica gel chromatography (75-100% CH2Cl2 in hexanes)

Sources & evidence

ORD record
ord-e5b3ae756091406ba1fab4b407a04d2b
Source dataset
uspto-grants-2011_10
Patent number
US08030304B2

Reaction notes

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