Potassium Carbonate → (1S,4S)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl(8-(1,3-oxazol-5-yl)-6-(trifluoromethyl) [1,2,4]triazolo[4,3-a]pyridin-3-yl)methanone

HRID 931011Notes

Reaction equation

HRID 931011 reaction equation
[C@H:1]12[CH2:23][C@H:4]([N:5]([C:7]([C:9]3[N:13]4[CH:14]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:16]=[C:17](Cl)[C:12]4=[N:11][N:10]=3)=[O:8])[CH2:6]1)[CH2:3][O:2]2.CC1(C)C(C)(C)OB([C:32]2[O:36][C:35]([Si](C(C)C)(C(C)C)C(C)C)=[N:34][CH:33]=2)O1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.O.O.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe]>[C@H:1]12[CH2:23][C@H:4]([N:5]([C:7]([C:9]3[N:13]4[CH:14]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:16]=[C:17]([C:32]5[O:36][CH:35]=[N:34][CH:33]=5)[C:12]4=[N:11][N:10]=3)=[O:8])[CH2:6]1)[CH2:3][O:2]2

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 442243115-(Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(tris(propan-2-yl)silyl)-1,3-oxazoleHCID 118378881(1S,4S)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl(8-chloro-6-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methanone

Product 1

HCID 118379043(1S,4S)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl(8-(1,3-oxazol-5-yl)-6-(trifluoromethyl) [1,2,4]triazolo[4,3-a]pyridin-3-yl)methanoneYield 31.8%

Reagents, catalysts & solvents 3

HCID 178477754HCID 178477754, compoundCatalystHCID 962WaterSolventHCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of (1S,4S)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl(8-chloro-6-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methanone (46 mg), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(triisopropylsilyl)oxazole (51 mg), [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (11 mg) and potassium carbonate (37 mg) in DME/water (2/0.5 mL) was stirred with microwave irradiation at 120° C. for 30 min. The reaction mixture was diluted with water, and extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was dissolved in THF (2 mL), and 1N hydrochloric acid (1 mL) was added thereto. The reaction mixture was stirred at room temperature for 1 hr, saturated aqueous sodium bicarbonate solution was added thereto, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane), and the obtained solid was recrystallized from ethyl acetate/hexane to give the title compound (16 mg).

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe extract was dried over anhydrous sodium sulfate
  3. customthe solvent was evaporated under reduced pressure
  4. dissolutionThe residue was dissolved in THF (2 mL)
  5. addition1N hydrochloric acid (1 mL) was added
  6. stirringThe reaction mixture was stirred at room temperature for 1 hr
  7. additionsaturated aqueous sodium bicarbonate solution was added
  8. extractionthe mixture was extracted with ethyl acetate
  9. dry with materialThe extract was dried over anhydrous magnesium sulfate
  10. customthe solvent was evaporated under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)
  12. customthe obtained solid was recrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-a0eb3ab9c88241d28b000e57994d2a63
Source dataset
uspto-grants-2016_03
Patent number
US09296746B2

Reaction notes

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