N,N-Dimethylaniline → 7-Chloro-5-methylthiopyrazolo[1,5-a]pyrimidine-6-carbonitrile

HRID 2037034Notes

Reaction equation

HRID 2037034 reaction equation
P(Cl)(Cl)([Cl:3])=O.CN(C)C1C=CC=CC=1.O[C:16]1[N:21]2[N:22]=[CH:23][CH:24]=[C:20]2[N:19]=[C:18]([S:25][CH3:26])[C:17]=1[C:27]#[N:28]>>[Cl:3][C:16]1[N:21]2[N:22]=[CH:23][CH:24]=[C:20]2[N:19]=[C:18]([S:25][CH3:26])[C:17]=1[C:27]#[N:28]

Participants

4

Reactant 3

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychlorideHCID 178503357HCID 178503357, compound

Product 1

HCID 220480807-Chloro-5-methylthiopyrazolo[1,5-a]pyrimidine-6-carbonitrileYield 80%

Conditions

Temperature
110 °C

Procedure

Under nitrogen gas atmosphere, phosphorous oxychloride (9.4 mL, 101.3 mmol) and dimethylaniline (2.6 mL, 20.3 mmol) was added successively to the intermediate, 7-hydroxy-5-(methylthio)pyrazolo[1,5-a]pyrimidine-6-carbonitrile, prepared above (4.1 g, 19.7 mmol). The mixture was heated at 110° C. for 4 hours then excess POCl3 was removed under vacuum. The residue was made basic with 3N NaOH solution (pH=9-10) and extracted with ethyl acetate (3×). The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated under vacuum. The residue was purified by recrystallization from ethyl acetate hexanes to provide the product, 7-chloro-5-(methylthio)pyrazolo[1,5-a]pyrimidine-6-carbonitrile (80% yield). LCMS (M+1=225)

Workup

  1. customprepared above (4.1 g, 19.7 mmol)
  2. customexcess POCl3 was removed under vacuum
  3. extractionextracted with ethyl acetate (3×)
  4. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by recrystallization from ethyl acetate hexanes

Sources & evidence

ORD record
ord-6973864ff1274daf9fd7141a2e9558a8
Source dataset
uspto-grants-2013_11
Patent number
US08575177B2

Reaction notes

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