1H-1,2,4-Triazole, 1-methyl- → 3-(4-Bromo-2-(2-methyl-2H-[1,2,4]triazol-3-yl)-thiazol-5-yl)-7-(1-ethyl-propyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine

HRID 1660744Notes

Reaction equation

HRID 1660744 reaction equation
C([Li])CCC.[CH3:6][N:7]1[CH:11]=[N:10][CH:9]=[N:8]1.Br[C:13]1[S:14][C:15]([C:19]2[C:20]([CH3:34])=[N:21][N:22]3[C:27]([CH:28]([CH2:31][CH3:32])[CH2:29][CH3:30])=[CH:26][C:25]([CH3:33])=[N:24][C:23]=23)=[C:16]([Br:18])[N:17]=1>C1COCC1.C(OCC)(=O)C.[Cl-].[Zn+2].[Cl-]>[Br:18][C:16]1[N:17]=[C:13]([C:11]2[N:7]([CH3:6])[N:8]=[CH:9][N:10]=2)[S:14][C:15]=1[C:19]1[C:20]([CH3:34])=[N:21][N:22]2[C:27]([CH:28]([CH2:29][CH3:30])[CH2:31][CH3:32])=[CH:26][C:25]([CH3:33])=[N:24][C:23]=12

Participants

7

Reactant 3

HCID 224591H-1,2,4-Triazole, 1-methyl-HCID 674295502,4-Dibromo-5-(2,5-dimethyl-7-(pentan-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)thiazoleHCID 178418339Butyllithium

Product 1

HCID 248989763-(4-Bromo-2-(2-methyl-2H-[1,2,4]triazol-3-yl)-thiazol-5-yl)-7-(1-ethyl-propyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidineYield 33.4%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Under nitrogen atmosphere, add n-butyl lithium (2.5 M in hexane, 0.6 mL, 1.5 mmol) to a solution of 1-methyl-1,2,4-triazole (124.5 mg, 1 5 mmol) in THF (3 mL) at −78° C. and stir for 30 min. Add anhydrous zinc chloride (409 mg, 3 0 mmol), continue stirring for 30 min, warm up to room temperature and stir for 2 h. Add 3-(2,4-dibromo-thiazol-5-yl)-7-(1-ethyl-propyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine (229 mg, 0.5 mmol), followed by tetrakis(triphenylphosine)palladium (58 mg, 0.05 mmol) and reflux overnight. Cool to room temperature, dilute with ethyl acetate, and wash with saturated ammonia chloride. Dry the organic portion over sodium sulfate, filter, and concentrate to a residue. Purify the crude material by flash chromatography, eluting with hexanes:ethyl acetate (10:2.5) to give the title compound as a yellow foam (77 mg). MS (APCI) m/z (79Br) 460.4 (M+1)+.

Workup

  1. stirringstir for 2 h
  2. temperaturereflux overnight
  3. temperatureCool to room temperature
  4. washwash with saturated ammonia chloride
  5. dry with materialDry the organic portion over sodium sulfate
  6. filtrationfilter
  7. concentrationconcentrate to a residue
  8. customPurify the crude material by flash chromatography
  9. washeluting with hexanes:ethyl acetate (10:2.5)

Sources & evidence

ORD record
ord-ae9514e516a14f6fbdd45ef397009a19
Source dataset
uspto-grants-2011_10
Patent number
US08030304B2

Reaction notes

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