Dimethylformamide → HCID 178433755, compound

HRID 2282220Notes

Reaction equation

HRID 2282220 reaction equation
[CH3:1][C:2]1[C:11]([C:12]2[S:13][C:14]([C:23]3[N:27]=[CH:26][N:25](C4CCCCO4)[N:24]=3)=[C:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[N:16]=2)=[C:5]2[CH:6]=[C:7]([OH:10])[CH:8]=[CH:9][N:4]2[N:3]=1.Cl[CH2:35][C:36]1[CH:37]=[CH:38][C:39]([C:42]([F:45])([F:44])[F:43])=[N:40][CH:41]=1.C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>CCOC(C)=O.O>[CH3:1][C:2]1[C:11]([C:12]2[S:13][C:14]([C:23]3[N:27]=[CH:26][NH:25][N:24]=3)=[C:15]([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[N:16]=2)=[C:5]2[CH:6]=[C:7]([O:10][CH2:35][C:36]3[CH:41]=[N:40][C:39]([C:42]([F:45])([F:43])[F:44])=[CH:38][CH:37]=3)[CH:8]=[CH:9][N:4]2[N:3]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 27738105-(Chloromethyl)-2-(trifluoromethyl)pyridineHCID 178433751HCID 178433751, compound

Product 1

HCID 178433755HCID 178433755, compoundYield 92%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 2-methyl-3-{4-phenyl-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-1,3-thiazol-2-yl}pyrazolo[1,5-a]pyridin-5-ol (100 mg, 0.22 mmol) obtained in Example 31-B(i), 5-(chloromethyl)-2-(trifluoromethyl)pyridine (64 mg, 0.33 mmol), potassium carbonate (60 mg, 0.44 mmol) and DMF (4 mL) was stirred at 60° C. for 2 h. Water (100 mL) and EtOAc (100 mL) were added to the reaction mixture, and the mixture was stirred for 30 min. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. Insoluble materials were removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was dissolved in MeOH (5 mL) and THF (30 mL), 6 N hydrochloric acid (3 mL) was added, and the mixture was stirred at 70° C. for 3 h. The reaction mixture was allowed to cool to rt, and the mixture was concentrated under reduced pressure. To the residue were added EtOAc (50 mL), THF (50 mL), 8 N aqueous sodium hydroxide solution (3 mL) and water (30 mL), and the mixture was stirred for 30 min. The organic layer was washed with brine and dried over anhydrous magnesium sulfate, and insoluble materials were removed by filtration. The filtrate was concentrated under reduced pressure. The residue was crystallized from EtOAc to give the title compound (107 mg, 92%) as a white solid.

Workup

  1. stirringthe mixture was stirred for 30 min
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customInsoluble materials were removed by filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. dissolutionThe residue was dissolved in MeOH (5 mL)
  7. additionTHF (30 mL), 6 N hydrochloric acid (3 mL) was added
  8. stirringthe mixture was stirred at 70° C. for 3 h
  9. temperatureto cool to rt
  10. concentrationthe mixture was concentrated under reduced pressure
  11. additionTo the residue were added EtOAc (50 mL), THF (50 mL), 8 N aqueous sodium hydroxide solution (3 mL) and water (30 mL)
  12. stirringthe mixture was stirred for 30 min
  13. washThe organic layer was washed with brine
  14. dry with materialdried over anhydrous magnesium sulfate, and insoluble materials
  15. customwere removed by filtration
  16. concentrationThe filtrate was concentrated under reduced pressure
  17. customThe residue was crystallized from EtOAc

Sources & evidence

ORD record
ord-4a634fe4f2864705925fd2a8634e0b22
Source dataset
uspto-grants-2015_09
Patent number
US09139589B2

Reaction notes

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