Ammonium Chloride → 7-(1-Propyl-butyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine

HRID 1660733Notes

Reaction equation

HRID 1660733 reaction equation
[Mg].Br[CH:3]([CH2:7][CH2:8][CH3:9])[CH2:4][CH2:5][CH3:6].Cl[C:11]1[N:16]2[N:17]=[C:18]([CH3:20])[CH:19]=[C:15]2[N:14]=[C:13]([CH3:21])[CH:12]=1.[Cl-].[NH4+]>C1COCC1.BrC(CCC)CCC.II>[CH2:4]([CH:3]([C:11]1[N:16]2[N:17]=[C:18]([CH3:20])[CH:19]=[C:15]2[N:14]=[C:13]([CH3:21])[CH:12]=1)[CH2:7][CH2:8][CH3:9])[CH2:5][CH3:6]

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 704604-BromoheptaneHCID 5462224Magnesium2×HCID 184069877-Chloro-2,5-dimethylpyrazolo(1,5-a)pyrimidine

Product 1

HCID 248985217-(1-Propyl-butyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidineYield 1,086.8%

Reagents, catalysts & solvents 3

HCID 807IodineCatalystHCID 704604-BromoheptaneCatalystHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

Heat a mixture of magnesium turnings (3.5 g, 144 mmol) and a catalytic amount of iodine (100 mg) in THF (100 mL) to 65° C. under a nitrogen atmosphere. Add a few drops of neat 4-bromoheptane and heat the mixture until the reaction starts. Then add a solution of 4-bromoheptane (17.6 mL, 94 9 mmol) in THF (42 mL) keeping the temperature at 65-70° C. over 2 h. Reflux the mixture for an additional hour and then cool the reaction to 22° C. Add the prepared Grignard reagent to a solution of 7-chloro-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine (10.2 g; 53 3 mmol) in THF (60 mL) cooled to 0° C. under a nitrogen atmosphere. Add the magnesium reagent solution via cannula over 45 min while keeping the temperature below 10° C. Then stir the mixture for an additional 30 min at 5° C. Add to this mixture a 10% aqueous ammonium chloride solution (wt/wt) (125 mL) and stir at 22° C. for 30 min. Separate the organic layer and extract the aqueous layer with ethyl acetate (2×25 mL). Combine the organic layers and dry over sodium sulfate. Filter the mixture and evaporate the solvent. Purify the crude material by silica gel flash chromatography using an eluent of hexanes/ethyl acetate (5/1) to provide the title compound (8 g, 62%). ES/MS m/z 246 (M+1)+.

Workup

  1. temperatureHeat
  2. customto 65° C.
  3. temperatureheat the mixture until the reaction
  4. customat 65-70° C.
  5. customover 2 h
  6. temperatureReflux the mixture for an additional hour
  7. temperaturecool
  8. customthe reaction to 22° C
  9. customthe temperature below 10° C
  10. stirringstir at 22° C. for 30 min
  11. customSeparate the organic layer
  12. extractionextract the aqueous layer with ethyl acetate (2×25 mL)
  13. dry with materialCombine the organic layers and dry over sodium sulfate
  14. filtrationFilter the mixture
  15. customevaporate the solvent
  16. customPurify the crude material by silica gel flash chromatography

Sources & evidence

ORD record
ord-ecf40c43b84e46a59e3ace2e80a87c17
Source dataset
uspto-grants-2011_10
Patent number
US08030304B2

Reaction notes

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