Ammonium Chloride → 7-(1-Ethyl-propyl)-3-(2-methoxymethyl-thiazol-5-yl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine

HRID 1660751Notes

Reaction equation

HRID 1660751 reaction equation
C([Li])CCC.[CH2:6]([CH:8]([C:11]1[N:16]2[N:17]=[C:18]([CH3:25])[C:19]([C:20]3[S:24][CH:23]=[N:22][CH:21]=3)=[C:15]2[N:14]=[C:13]([CH3:26])[CH:12]=1)[CH2:9][CH3:10])[CH3:7].[CH3:27][O:28][CH2:29]I.[Cl-].[NH4+]>C1COCC1>[CH2:6]([CH:8]([C:11]1[N:16]2[N:17]=[C:18]([CH3:25])[C:19]([C:20]3[S:24][C:23]([CH2:27][O:28][CH3:29])=[N:22][CH:21]=3)=[C:15]2[N:14]=[C:13]([CH3:26])[CH:12]=1)[CH2:9][CH3:10])[CH3:7]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 139376Iodomethyl methyl etherHCID 674299217-(1-Ethyl-propyl)-2,5-dimethyl-3-thiazol-5-yl-pyrazolo[1,5-a]pyrimidineHCID 178418339Butyllithium

Product 1

HCID 674280047-(1-Ethyl-propyl)-3-(2-methoxymethyl-thiazol-5-yl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidineYield 53.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Under a nitrogen atmosphere, add n-butyl lithium (2.5 M in hexane, 0.4 mL, 1.0 mmol) to a solution of 7-(1-ethyl-propyl)-2,5-dimethyl-3-thiazol-5-yl-pyrazolo[1,5-a]pyrimidine (300 mg, 1.0 mmol) in THF (3 mL) at −78° C. Stir 30 min and add 1-iodomethyl methyl ether (205 mg, 1.2 mmol). Continue stirring for one hour and then slowly warm up to room temperature and stir overnight. Quench the reaction by adding saturated ammonium chloride solution and extract with ethyl acetate. Wash the organic layer with brine, dry over sodium sulfate, filter, and concentrate under vacuum to a residue. Purify the crude material by flash chromatography, eluting with hexanes/ethyl acetate (10/2) to give the title compound as a yellow foam (184 mg). MS (APCI) m/z 345.3 (M+1)+.

Workup

  1. stirringContinue stirring for one hour
  2. stirringstir overnight
  3. customQuench
  4. customthe reaction
  5. extractionextract with ethyl acetate
  6. washWash the organic layer with brine
  7. dry with materialdry over sodium sulfate
  8. filtrationfilter
  9. concentrationconcentrate under vacuum to a residue
  10. customPurify the crude material by flash chromatography
  11. washeluting with hexanes/ethyl acetate (10/2)

Sources & evidence

ORD record
ord-f6926211565b4335b21e8343b767da51
Source dataset
uspto-grants-2011_10
Patent number
US08030304B2

Reaction notes

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