Water → 2,5-Dimethyl-3-[2-(2-methyl-2H-[1,2,4]triazol-3-yl)-thiazol-5-yl]-7-(1-propyl-butyl)-pyrazolo[1,5-a]pyrimidine

HRID 1660738Notes

Reaction equation

HRID 1660738 reaction equation
Br[C:2]1[S:6][C:5]([C:7]2[N:11]([CH3:12])[N:10]=[CH:9][N:8]=2)=[N:4][CH:3]=1.[CH3:13][C:14]1[CH:30]=[C:17]2[N:18]=[C:19]([CH3:29])[CH:20]=[C:21]([CH:22]([CH2:26][CH2:27][CH3:28])[CH2:23][CH2:24][CH3:25])[N:16]2[N:15]=1.C([O-])(=O)C.[K+].O>CN1CCCC1=O.CCCC[N+](CCCC)(CCCC)CCCC.[Br-].C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(C1C=C(C(C)(C)C)C=CC=1P(C1C=CC(C(C)(C)C)=CC=1C(C)(C)C)C1C=CC(C(C)(C)C)=CC=1C(C)(C)C)(C)(C)C>[CH3:13][C:14]1[C:30]([C:2]2[S:6][C:5]([C:7]3[N:11]([CH3:12])[N:10]=[CH:9][N:8]=3)=[N:4][CH:3]=2)=[C:17]2[N:18]=[C:19]([CH3:29])[CH:20]=[C:21]([CH:22]([CH2:26][CH2:27][CH3:28])[CH2:23][CH2:24][CH3:25])[N:16]2[N:15]=1

Participants

9

Reactant 4

HCID 962WaterHCID 517044Potassium AcetateHCID 248985217-(1-Propyl-butyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidineHCID 534011685-Bromo-2-(1-methyl-1H-1,2,4-triazol-5-yl)thiazole

Product 1

HCID 674286482,5-Dimethyl-3-[2-(2-methyl-2H-[1,2,4]triazol-3-yl)-thiazol-5-yl]-7-(1-propyl-butyl)-pyrazolo[1,5-a]pyrimidineYield 341.8%

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalystHCID 167845palladium(II) acetateCatalystHCID 15860411Tris(2,4-di-tert-butylphenyl)phosphaneCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
125 °C

Procedure

Combine 5-(5-bromo-thiazol-2-yl)-1-methyl-1H-[1,2,4]triazole (6.5 g, 23 8 mmol) and 2,5-dimethyl-7-(1-propyl-butyl)-pyrazolo[1,5-a]pyrimidine (6 g, 24 5 mmol) in N-methylpyrrolidinone (58 mL) and stir to complete solution under nitrogen. Then add tetra-N-butylammonium bromide (5.47 g, 16.7 mmol) and potassium acetate (11.8 g, 119 mmol) and heat the mixture to 100° C. under a nitrogen atmosphere. Degas the hot mixture by three cycles of vacuum/nitrogen purge. Then add palladium acetate (216 mg, 0.94 mmol) and tris(2,4-di-tert-butyl-phenyl)-phosphane (787 mg, 1.2 mmol). Heat the mixture 4 h at 125° C. under nitrogen. Cool the mixture to 22° C. and add to water (750 mL). Extract the aqueous layer with methyl-t-butyl ether (3×200 mL), combine the organic portions, and evaporate. Purify the residue by filtration through a silica gel pad eluting with hexanes/ethyl acetate (4/1). Combine the product containing fractions and evaporate the solvent to afford the title compound (7 g, 72%). ES/MS m/z 410 (M+1)+.

Workup

  1. customDegas the hot mixture by three cycles of vacuum/nitrogen
  2. custompurge
  3. temperatureCool the mixture to 22° C.
  4. extractionExtract the aqueous layer with methyl-t-butyl ether (3×200 mL)
  5. customevaporate
  6. customPurify the residue
  7. filtrationby filtration through a silica gel pad
  8. washeluting with hexanes/ethyl acetate (4/1)
  9. additionCombine the product containing fractions
  10. customevaporate the solvent

Sources & evidence

ORD record
ord-02069114a8714e0e96004dc20ce9c877
Source dataset
uspto-grants-2011_10
Patent number
US08030304B2

Reaction notes

Loading…