3,3,3-Trifluoropropionyl chloride → 2-(4-Chloro-phenyl)-5-{3-methoxy-4-[1-(3,3,3-trifluoro-propionyl)-azetidin-3-yloxy]-phenyl]-6,7-dihydro-5H-thiazolo[5,4-c]pyridin-4-one

HRID 554877Notes

Reaction equation

HRID 554877 reaction equation
[NH:1]1[CH2:4][CH:3]([O:5][C:6]2[CH:11]=[CH:10][C:9]([N:12]3[CH2:17][CH2:16][C:15]4[N:18]=[C:19]([C:21]5[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=5)[S:20][C:14]=4[C:13]3=[O:28])=[CH:8][C:7]=2[O:29][CH3:30])[CH2:2]1.[F:31][C:32]([F:38])([F:37])[CH2:33][C:34](Cl)=[O:35]>N1C=CC=CC=1>[Cl:27][C:24]1[CH:23]=[CH:22][C:21]([C:19]2[S:20][C:14]3[C:13](=[O:28])[N:12]([C:9]4[CH:10]=[CH:11][C:6]([O:5][CH:3]5[CH2:4][N:1]([C:34](=[O:35])[CH2:33][C:32]([F:38])([F:37])[F:31])[CH2:2]5)=[C:7]([O:29][CH3:30])[CH:8]=4)[CH2:17][CH2:16][C:15]=3[N:18]=2)=[CH:26][CH:25]=1

Participants

4

Reactant 2

HCID 27833433,3,3-Trifluoropropionyl chlorideHCID 249911625-[4-(azetidin-3-yloxy)-3-methoxy-phenyl]-2-(4-chloro-phenyl)-6,7-dihydro-5H-thiazolo[5,4-c]pyridin-4-one

Product 1

HCID 249911672-(4-Chloro-phenyl)-5-{3-methoxy-4-[1-(3,3,3-trifluoro-propionyl)-azetidin-3-yloxy]-phenyl]-6,7-dihydro-5H-thiazolo[5,4-c]pyridin-4-oneYield 70.5%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Dissolve 5-[4-(azetidin-3-yloxy)-3-methoxy-phenyl]-2-(4-chloro-phenyl)-6,7-dihydro-5H-thiazolo[5,4-c]pyridin-4-one (100 mg, 0.226 mmol), and 3,3,3-trifluoropropionyl chloride (137 mg, 0.905 mmol) in dry pyridine (754.3 μL). Add 4-N,N-dimethylpyridine (2.9 mg, 0.0226 mmol) and stir the solution overnight. Add NaHSO4 solution and extract with EtOAc (2×20 mL). Combine the organic portions and wash with water (10 mL). Dry the organic solution with Na2SO4, filter, and concentrate in vacuo. Purify the crude material on silica gel chromatography, using an isocratic gradient of 80% EtOAc in hexanes, to give 88 mg (70%) of the title compound as a yellow solid. ES/MS m/z (35Cl) 552.8 [M+1]−.

Workup

  1. extractionAdd NaHSO4 solution and extract with EtOAc (2×20 mL)
  2. washCombine the organic portions and wash with water (10 mL)
  3. dry with materialDry the organic solution with Na2SO4
  4. filtrationfilter
  5. concentrationconcentrate in vacuo
  6. customPurify the crude material on silica gel chromatography

Sources & evidence

ORD record
ord-dcbd50fd93b3469bac734452086fc183
Source dataset
uspto-grants-2011_11
Patent number
US08049013B2

Reaction notes

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