Water → 2-(4-trifluoromethyl-phenyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide

HRID 1898650Notes

Reaction equation

HRID 1898650 reaction equation
[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:42])[C@H:8]([NH:12][C:13]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[C:21]([C:24]4[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][CH:25]=4)[N:22]=3)[N:17](COCC[Si](C)(C)C)[CH:16]=2)=[O:14])[CH:9]2[CH2:11][CH2:10]2)[CH2:4]1)#[N:2].FC(F)(F)C(O)=O.C([O-])(=O)C.[Na+].O>ClCCl.C(OCC)(=O)C>[C:1]([CH:3]1[CH2:4][N:5]([C:7](=[O:42])[C@H:8]([NH:12][C:13]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[C:21]([C:24]4[CH:25]=[CH:26][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:28][CH:29]=4)[N:22]=3)[NH:17][CH:16]=2)=[O:14])[CH:9]2[CH2:11][CH2:10]2)[CH2:6]1)#[N:2]

Participants

7

Reactant 4

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 517045Sodium AcetateHCID 673864092-(4-trifluoromethylphenyl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide

Product 1

HCID 533857442-(4-trifluoromethyl-phenyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amideYield 70%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-(4-Trifluoromethylphenyl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide (62 mg, 0.104 mmol) was dissolved in 0.8 mL of dichloromethane and then stirred in an ice bath. Trifluoroacetic acid (0.4 mL) was added slowly and the ice bath was removed. The reaction was stirred for 2.5 h and then cooled in ice bath. Sodium bicarbonate solution was added and the mixture was extracted three times with ethyl acetate. The combined organic layers were washed with brine and dried over sodium sulfate. After evaporation, the residue was dissolved in 4 mL of absolute ethanol, sodium acetate (170 mg, 2.07 mmol) was added and the mixture was stirred at 60° C. for overnight. The reaction was cooled, and water and ethyl acetate were added. The layers were separated and the aqueous layer was extracted twice more with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and evaporated. The residue was purified by silica gel chromatography (methanol/dichloromethane) to give 34 mg (70%) of 2-(4-trifluoromethyl-phenyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide. MS: (M+H)+=469; mp=207-209° C.

Workup

  1. customthe ice bath was removed
  2. stirringThe reaction was stirred for 2.5 h
  3. temperaturecooled in ice bath
  4. additionSodium bicarbonate solution was added
  5. extractionthe mixture was extracted three times with ethyl acetate
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over sodium sulfate
  8. customAfter evaporation
  9. dissolutionthe residue was dissolved in 4 mL of absolute ethanol
  10. stirringthe mixture was stirred at 60° C. for overnight
  11. temperatureThe reaction was cooled
  12. customThe layers were separated
  13. extractionthe aqueous layer was extracted twice more with ethyl acetate
  14. washThe combined organic layers were washed with brine
  15. dry with materialdried over sodium sulfate
  16. customevaporated
  17. customThe residue was purified by silica gel chromatography (methanol/dichloromethane)

Sources & evidence

ORD record
ord-8f73841ef419462e9997f586d3fac934
Source dataset
uspto-grants-2013_08
Patent number
US08518945B2

Reaction notes

Loading…