Ethyl cyanoformate → 4-Chloro-5-[7-(1-ethyl-propyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-3-yl]-thiophene-2-carboxylic acid ethyl ester

HRID 1639660Notes

Reaction equation

HRID 1639660 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.C([Mg]Cl)C.[CH2:28]([O:30][C:31](C#N)=[O:32])[CH3:29]>C1COCC1>[CH2:28]([O:30][C:31]([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)=[O:32])[CH3:29]

Participants

5

Reactant 3

HCID 69336Ethyl cyanoformateHCID 248987433-(5-Bromo-3-chloro-thiophene-2-yl)-7-(1-ethyl-propyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidineHCID 178461633HCID 178461633, compound

Product 1

HCID 248989754-Chloro-5-[7-(1-ethyl-propyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-3-yl]-thiophene-2-carboxylic acid ethyl esterYield 19%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Chill to 0° C. a mixture of 3-(5-bromo-3-chloro-thiophene-2-yl)-7-(1-ethyl-propyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidine (0.62 g, 1.5 mmol) in anhydrous THF (5 mL) under an inert atmosphere and add ethyl magnesium chloride (2 M THF solution, 0.83 mL, 1.65 mmol). Stir the reaction 5 min, warm to room temperature, and stir an additional 15 min before lowering the reaction temperature to 0° C. Add ethylcyanoformate (0.16 mL, 1.58 mmol) diluted in anhydrous THF (1 mL). Warm the reaction to room temperature and stir 1 h. Quench the reaction with saturated sodium bicarbonate (20 mL) and extract with ether (2×75 mL). Combine the organic portions, dry over anhydrous magnesium sulfate, filter, and concentrate under reduced pressure. Purify using flash chromatography, eluting with 100% hexane/0% (20% ethyl acetate/hexane) to 0% hexane/100% (20% ethyl acetate/hexane) in a step gradient of 10% increments. Dry the resulting material under vacuum to provide a white solid (0.114 g, 19%). ES/MS m/z (35Cl) 406.3 (M+1)+.

Workup

  1. customthe reaction 5 min
  2. temperaturewarm to room temperature
  3. stirringstir an additional 15 min
  4. customto 0° C
  5. temperatureWarm
  6. customthe reaction to room temperature
  7. stirringstir 1 h
  8. customQuench
  9. customthe reaction with saturated sodium bicarbonate (20 mL)
  10. extractionextract with ether (2×75 mL)
  11. dry with materialCombine the organic portions, dry over anhydrous magnesium sulfate
  12. filtrationfilter
  13. concentrationconcentrate under reduced pressure
  14. customPurify
  15. washeluting with 100% hexane/0% (20% ethyl acetate/hexane) to 0% hexane/100% (20% ethyl acetate/hexane) in a step gradient of 10% increments
  16. customDry the resulting material under vacuum

Sources & evidence

ORD record
ord-3e20752e48a74063b03a0d6e144b5c84
Source dataset
uspto-grants-2012_02
Patent number
US08110580B2

Reaction notes

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