Sodium Iodide → 3-(3-Chloro-5-methoxy-thiophene-2-yl)-7-(1-ethyl-propyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine

HRID 1639659Notes

Reaction equation

HRID 1639659 reaction equation
Br[C:2]1[S:6][C:5]([C:7]2[C:8]([CH3:22])=[N:9][N:10]3[C:15]([CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])=[CH:14][C:13]([CH3:21])=[N:12][C:11]=23)=[C:4]([Cl:23])[CH:3]=1.[I-].[Na+].[CH3:26][O-:27].[Na+].CO>[Cu]=O.CO>[Cl:23][C:4]1[CH:3]=[C:2]([O:27][CH3:26])[S:6][C:5]=1[C:7]1[C:8]([CH3:22])=[N:9][N:10]2[C:15]([CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])=[CH:14][C:13]([CH3:21])=[N:12][C:11]=12

Participants

6

Reactant 3

HCID 5238Sodium IodideHCID 23694274Sodium methanolate methanolHCID 248987433-(5-Bromo-3-chloro-thiophene-2-yl)-7-(1-ethyl-propyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine

Product 1

HCID 248989733-(3-Chloro-5-methoxy-thiophene-2-yl)-7-(1-ethyl-propyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidineYield 21%

Reagents, catalysts & solvents 2

HCID 14829Copper oxideCatalystHCID 887MethanolSolvent

Procedure

Charge an oven dried flask with 3-(5-bromo-3-chloro-thiophene-2-yl)-7-(1-ethyl-propyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine (0.46 g, 1.1 mmol), copper oxide (0.045 g, 0.56 mmol), sodium iodide (0.020 g, 0.11 mmol), 25% sodium methoxide/methanol solution (10 mL) and anhydrous methanol (10 mL). Reflux the reaction in an oil bath (90° C.) over the weekend under an inert atmosphere. Quench the reaction with ice water and extract with ether (3×100 mL). Combine the organic portions, dry over anhydrous magnesium sulfate, filter, and concentrate under reduced pressure. Purify the resulting residue using flash chromatography, eluting with 100% hexane/0% (35% ethyl acetate/hexane) to 0% hexane/100% (35% ethyl acetate/hexane) in a step gradient of 10% increments to give a white foam (0.086 g, 21%). ES/MS m/z (35Cl) 363.7 (M+1)+.

Workup

  1. additionCharge an oven
  2. temperatureReflux
  3. customthe reaction in an oil bath (90° C.) over the weekend under an inert atmosphere
  4. customQuench
  5. customthe reaction with ice water
  6. extractionextract with ether (3×100 mL)
  7. dry with materialCombine the organic portions, dry over anhydrous magnesium sulfate
  8. filtrationfilter
  9. concentrationconcentrate under reduced pressure
  10. customPurify the resulting residue
  11. washeluting with 100% hexane/0% (35% ethyl acetate/hexane) to 0% hexane/100% (35% ethyl acetate/hexane) in a step gradient of 10% increments

Sources & evidence

ORD record
ord-f70fd44164e44b57a93cae7449b360bd
Source dataset
uspto-grants-2012_02
Patent number
US08110580B2

Reaction notes

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