Lithium Hydroxide → N-{5-[3-(2-chloropyrimidin-4-yl)pyrazolo[1,5-a]pyridin-2-yl]-2-methoxyphenyl}-2-(2-thienyl)acetamide

HRID 1157609Notes

Reaction equation

HRID 1157609 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[C:9]([C:17]3[CH:18]=[CH:19][C:20]([O:30][CH3:31])=[C:21]([NH:23][C:24](=[O:29])[C:25](F)(F)F)[CH:22]=3)=[N:10][N:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=23)[CH:5]=[CH:4][N:3]=1.[Li+].[OH-].C1COCC1.[CH:39]1[CH:43]=[C:42](CC(Cl)=O)[S:41][CH:40]=1>O>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[C:9]([C:17]3[CH:18]=[CH:19][C:20]([O:30][CH3:31])=[C:21]([NH:23][C:24](=[O:29])[CH2:25][C:40]4[S:41][CH:42]=[CH:43][CH:39]=4)[CH:22]=3)=[N:10][N:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=23)[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 1623622-Thiopheneacetyl chlorideHCID 59511425N-[5-[3-(2-Chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]-2-(methyloxy)phenyl]-2,2,2-trifluoroacetamide

Product 1

HCID 57737232N-{5-[3-(2-chloropyrimidin-4-yl)pyrazolo[1,5-a]pyridin-2-yl]-2-methoxyphenyl}-2-(2-thienyl)acetamideYield 79%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A solution of N-[5-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]-2-(methyloxy)phenyl]-2,2,2-trifluoroacetamide (250 mg, 0.56 mmol) and 1M LiOH (1.30 mL, 1.39 mmol) in 10:1 THF:H2O (5 mL) was heated at 50° C. overnight. After removal of THF by rotary evaporation, the reaction mixture was redissolved in EtOAc and washed with water (25 mL) and brine (25 mL). The organic layer was dried over MgSO4. Following filtration, the solvent was removed by rotary evaporation. After high vacuum removal of the residual solvent, the crude mixture was dissolved in THF (5 mL) and to this was added thiophene-2-acetylchloride (0.10 mL, 0.84 mmol). After overnight stirring, water (0.5 mL) was added and THF removed by rotary evaporation. The reaction mixture was redissolved in DCM (25 mL) washed with saturated NaHCO3 (10 mL), water (10 mL) and brine (10 mL). Organics were dried over MgSO4, filtered and filtrate concentrated under reduced pressure to afford the desired amide (210 mg, 79%) as an off-white solid. ES-LC/MS m/z=476 [M+H]−.

Workup

  1. customAfter removal of THF
  2. customby rotary evaporation
  3. dissolutionthe reaction mixture was redissolved in EtOAc
  4. washwashed with water (25 mL) and brine (25 mL)
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltration
  7. customthe solvent was removed by rotary evaporation
  8. customAfter high vacuum removal of the residual solvent
  9. dissolutionthe crude mixture was dissolved in THF (5 mL)
  10. customTHF removed by rotary evaporation
  11. dissolutionThe reaction mixture was redissolved in DCM (25 mL)
  12. washwashed with saturated NaHCO3 (10 mL), water (10 mL) and brine (10 mL)
  13. dry with materialOrganics were dried over MgSO4
  14. filtrationfiltered
  15. concentrationfiltrate concentrated under reduced pressure

Sources & evidence

ORD record
ord-91b35b6a88774952ae4c8336ce8319fd
Source dataset
uspto-grants-2010_10
Patent number
US07807673B2

Reaction notes

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