2-Amino-3-methylpyridine → HCID 49869936, compound

HRID 1631312Notes

Reaction equation

HRID 1631312 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C@H:9]1[CH2:13][CH2:12][CH2:11][N:10]1[C:14]1[CH:19]=[CH:18][N:17]2[N:20]=[CH:21][C:22]([C:23](O)=[O:24])=[C:16]2[N:15]=1.S(Cl)(Cl)=O.[NH2:30][C:31]1[C:36]([CH3:37])=[CH:35][CH:34]=[CH:33][N:32]=1>C(Cl)(Cl)(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C@H:9]1[CH2:13][CH2:12][CH2:11][N:10]1[C:14]1[CH:19]=[CH:18][N:17]2[N:20]=[CH:21][C:22]([C:23]([NH:30][C:31]3[C:36]([CH3:37])=[CH:35][CH:34]=[CH:33][N:32]=3)=[O:24])=[C:16]2[N:15]=1

Participants

5

Reactant 3

HCID 153472-Amino-3-methylpyridineHCID 24386Thionyl ChlorideHCID 66847716(R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid

Product 1

HCID 49869936HCID 49869936, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 5943Carbon TetrachlorideSolvent

Procedure

To a suspension of (R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (Preparation C, 25.0 mg, 0.072 mmol) in CCl4 (1.0 mL) was added thionyl chloride (0.10 mL) and the mixture heated at reflux for 4 hours. The mixture was cooled to ambient temperature and was concentrated to a brittle foam. The foam was dissolved in pyridine (2 mL), 2-amino-3-methyl-pyridine (9.3 mg, 0.086 mmol) was added and the mixture was heated at 90° C. for 20 hours. The reaction was cooled to ambient temperature and the pyridine evaporated. The residue was partitioned into 1M NaOH and EtOAc, mixed and the EtOAc layer removed. The aqueous layer was extracted with EtOAc and combined EtOAc fractions were washed with H2O, saturated NaCl and dried over MgSO4. The solution was filtered and concentrated, and the resulting solid was washed with dry Et2O to afford the title compound as a white solid (7 mg, 29%). MS (apci) m/z=435.1 (M+H).

Workup

  1. temperaturethe mixture heated
  2. temperatureat reflux for 4 hours
  3. concentrationwas concentrated to a brittle foam
  4. dissolutionThe foam was dissolved in pyridine (2 mL)
  5. temperaturethe mixture was heated at 90° C. for 20 hours
  6. temperatureThe reaction was cooled to ambient temperature
  7. customthe pyridine evaporated
  8. customThe residue was partitioned into 1M NaOH and EtOAc
  9. additionmixed
  10. customthe EtOAc layer removed
  11. extractionThe aqueous layer was extracted with EtOAc and combined EtOAc fractions
  12. washwere washed with H2O, saturated NaCl
  13. dry with materialdried over MgSO4
  14. filtrationThe solution was filtered
  15. concentrationconcentrated
  16. washthe resulting solid was washed with dry Et2O

Sources & evidence

ORD record
ord-50ce0a64eee04716b2d3698f595dbd68
Source dataset
uspto-grants-2014_07
Patent number
US08791123B2

Reaction notes

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