Sodium Carbonate → 7-Chloro-2-(1,1-difluoropropyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidine

HRID 591227Notes

Reaction equation

HRID 591227 reaction equation
[F:1][C:2]([C:6]1[N:16]=[C:9]2[N:10]=[C:11]([CH3:15])[CH:12]=[C:13](O)[N:8]2[N:7]=1)([F:5])[CH2:3][CH3:4].P(Cl)(Cl)([Cl:19])=O.C([O-])([O-])=O.[Na+].[Na+]>O>[Cl:19][C:13]1[N:8]2[N:7]=[C:6]([C:2]([F:5])([F:1])[CH2:3][CH3:4])[N:16]=[C:9]2[N:10]=[C:11]([CH3:15])[CH:12]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 24813Phosphorus oxychlorideHCID 178455691HCID 178455691, compound

Product 1

HCID 533919807-Chloro-2-(1,1-difluoropropyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A suspension of Intermediate 6 (0.660 g, 2.89 mmol) in phosphorus oxychloride (ALDRICH, 0.404 mL, 43.4 mmol) was heated under reflux for 2 h, the starting material dissolving during the process. The mixture was slowly added to a mixture of water and ice. The resulting solution was neutralized with solid Na2CO3 and extracted with DCM (25 mL). The aqueous layer was further extracted with DCM (2×5 mL) and the combined organic layers were washed with water (20 mL); then with brine (20 mL), and dried over MgSO4. Solvent was removed under reduced pressure and the crude product was purified (silica gel column, eluting with Hexane/EtOAc mixtures from 100:0 to 40:60%) to afford Intermediate 7 as a pale yellow solid.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 2 h
  3. dissolutionthe starting material dissolving during the process
  4. extractionextracted with DCM (25 mL)
  5. extractionThe aqueous layer was further extracted with DCM (2×5 mL)
  6. washthe combined organic layers were washed with water (20 mL)
  7. dry with materialthen with brine (20 mL), and dried over MgSO4
  8. customSolvent was removed under reduced pressure
  9. customthe crude product was purified
  10. wash(silica gel column, eluting with Hexane/EtOAc mixtures from 100:0 to 40:60%)

Sources & evidence

ORD record
ord-55330ab32236469aac873ee01579a28c
Source dataset
uspto-grants-2016_01
Patent number
US09238653B2

Reaction notes

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