N,N-Dimethylaniline → 7-Chloro-5-(tetrahydro-2H-thiopyran-4-yl)pyrazolo[1,5-a]pyrimidine

HRID 1913207Notes

Reaction equation

HRID 1913207 reaction equation
[S:1]1[CH2:6][CH2:5][CH:4]([C:7]2[CH:12]=[C:11](O)[N:10]3[N:14]=[CH:15][CH:16]=[C:9]3[N:8]=2)[CH2:3][CH2:2]1.CN(C)C1C=CC=CC=1.P(Cl)(Cl)([Cl:28])=O>>[Cl:28][C:11]1[N:10]2[N:14]=[CH:15][CH:16]=[C:9]2[N:8]=[C:7]([CH:4]2[CH2:5][CH2:6][S:1][CH2:2][CH2:3]2)[CH:12]=1

Participants

4

Reactant 3

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychlorideHCID 178515710HCID 178515710, compound

Product 1

HCID 866678347-Chloro-5-(tetrahydro-2H-thiopyran-4-yl)pyrazolo[1,5-a]pyrimidine

Conditions

Temperature
50 °C

Procedure

To a mixture of 5-(tetrahydro-2H-thiopyran-4-yl)pyrazolo[1,5-a]pyrimidin-7-ol (Int-1b, 1.50 g, 6.38 mmol) and dimethylaniline (2.0 mL, 15 mml) was added phosphoryl trichloride (20 mL). The mixture was heated at 50° C. for 5 h and concentrated. The residue was diluted with methylene chloride (50 mL) and quenched with saturated NaHCO3 (50 mL). The mixture was separated and the aqueous layer was extracted with methylene chloride (50 mL×2). The combined organic layers were dried over Na2SO4, filtered and concentrated. The residue was purified by Biotage (CH2Cl2/EtOAc, 20:1 to 4:1). LC/MS RT=1.92 Min (5 min method). Mass calculated for, M+H 254.04, observed 254.04.

Workup

  1. concentrationconcentrated
  2. additionThe residue was diluted with methylene chloride (50 mL)
  3. customquenched with saturated NaHCO3 (50 mL)
  4. customThe mixture was separated
  5. extractionthe aqueous layer was extracted with methylene chloride (50 mL×2)
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by Biotage (CH2Cl2/EtOAc, 20:1 to 4:1)
  10. customLC/MS RT=1.92 Min (5 min method)

Sources & evidence

ORD record
ord-f2a95196c1c6450182c2946061e88699
Source dataset
uspto-grants-2013_12
Patent number
US08609675B2

Reaction notes

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