2-Dimethylaminopyridine → HCID 56944947, compound

HRID 1631353Notes

Reaction equation

HRID 1631353 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@H:8]2[CH2:12][CH2:11][CH2:10][N:9]2[C:13]2[CH:18]=[CH:17][N:16]3[N:19]=[CH:20][C:21]([C:22](O)=[O:23])=[C:15]3[N:14]=2)[CH:5]=[CH:6][CH:7]=1.S(Cl)(Cl)=O.C[N:30](C1C=CC=CN=1)C>C(Cl)(Cl)(Cl)Cl.C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([C@H:8]2[CH2:12][CH2:11][CH2:10][N:9]2[C:13]2[CH:18]=[CH:17][N:16]3[N:19]=[CH:20][C:21]([C:22]([NH2:30])=[O:23])=[C:15]3[N:14]=2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 218852-DimethylaminopyridineHCID 24386Thionyl ChlorideHCID 66692883HCID 66692883, compound

Product 1

HCID 56944947HCID 56944947, compoundYield 376.8%

Reagents, catalysts & solvents 2

HCID 5943Carbon TetrachlorideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of (R)-5-(2-(3-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (Preparation E, 50.0 mg, 0.153 mmol) in CCl4 (1.0 mL) was added thionyl chloride (182 mg, 1.53 mmol) and the mixture was heated at reflux for 4 hours (homogeneous after 5 minutes). The mixture was cooled to ambient temperature and was concentrated to give a brittle foam. The foam was dissolved in dry THF (2 mL) and dimethylaminopyridine (DMAP) (3.74 mg, 0.031 mmol) was added. Anhydrous ammonia was bubbled into the mixture with stirring for 5 minutes. The reaction vessel was sealed and the reaction was stirred at ambient temperature for 18 hours. The mixture was added to H2O (4 mL) and extracted with EtOAc. The combined extracts were washed with 1M Na2CO3, H2O and saturated NaCl. The solution was dried over MgSO4/activated carbon and filtered through a SiO2 plug (EtOAc then 10% MeOH/EtOAc for elution). The solution was concentrated to give the title compound as a white solid (38 mg, 76%). MS (apci) m/z=326.0 (M+H).

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 4 hours (homogeneous after 5 minutes)
  3. concentrationwas concentrated
  4. customto give a brittle foam
  5. customAnhydrous ammonia was bubbled into the mixture
  6. customThe reaction vessel was sealed
  7. stirringthe reaction was stirred at ambient temperature for 18 hours
  8. additionThe mixture was added to H2O (4 mL)
  9. extractionextracted with EtOAc
  10. washThe combined extracts were washed with 1M Na2CO3, H2O and saturated NaCl
  11. dry with materialThe solution was dried over MgSO4/activated carbon
  12. filtrationfiltered through a SiO2 plug (EtOAc
  13. wash10% MeOH/EtOAc for elution)
  14. concentrationThe solution was concentrated

Sources & evidence

ORD record
ord-8d71fae708c849c4afd2926f4e64d06e
Source dataset
uspto-grants-2014_07
Patent number
US08791123B2

Reaction notes

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