Water → 2-(2-chlorothiazol-5-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-cyano-piperidine-1-carbonyl)-2,2-dimethyl-propyl]-amide

HRID 1898646Notes

Reaction equation

HRID 1898646 reaction equation
[C:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9]([C@H:11]([NH:16][C:17]([C:19]2[C:27]3[C:22](=[N:23][CH:24]=[C:25]([C:28]4[S:32][C:31]([Cl:33])=[N:30][CH:29]=4)[N:26]=3)[N:21](COCC[Si](C)(C)C)[CH:20]=2)=[O:18])[C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][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][CH2:5][N:6]([C:9]([C@H:11]([NH:16][C:17]([C:19]2[C:27]3[C:22](=[N:23][CH:24]=[C:25]([C:28]4[S:32][C:31]([Cl:33])=[N:30][CH:29]=4)[N:26]=3)[NH:21][CH:20]=2)=[O:18])[C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:7][CH2:8]1)#[N:2]

Participants

7

Reactant 4

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 517045Sodium AcetateHCID 673860192-(2-chlorothiazol-5-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-cyano-piperidine-1-carbonyl)-2,2-dimethyl-propyl]-amide

Product 1

HCID 533856922-(2-chlorothiazol-5-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-cyano-piperidine-1-carbonyl)-2,2-dimethyl-propyl]-amideYield 26.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-(2-Chlorothiazol-5-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-cyano-piperidine-1-carbonyl)-2,2-dimethyl-propyl]-amide (39 mg, 0.063 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 (104 mg, 1.27 mmol) was added and the mixture was stirred at 60° C. for 20 h. 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. Purification by reverse phase chromatography afforded 8 mg (26%) of 2-(2-chlorothiazol-5-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-cyano-piperidine-1-carbonyl)-2,2-dimethyl-propyl]-amide. MS: (M+Na)+=509.

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 20 h
  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. customPurification by reverse phase chromatography

Sources & evidence

ORD record
ord-11346deb31c24754af990ebc5fdbadae
Source dataset
uspto-grants-2013_08
Patent number
US08518945B2

Reaction notes

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