Sodium Thiosulfate → 2-(6-fluoro-3-methanesulfonyl-imidazo[1,5-a]pyridin-1-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide

HRID 245877Notes

Reaction equation

HRID 245877 reaction equation
[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:42])[C@H:8]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([C:22]4[N:23]=[C:24](SC)[N:25]5[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=45)[N:20]=3)[N:15]([CH2:34][O:35][CH2:36][CH2:37][Si:38]([CH3:41])([CH3:40])[CH3:39])[CH:14]=2)=[O:12])[CH3:9])[CH2:4]1)#[N:2].[CH:43]1C=C(Cl)C=C(C(OO)=O)C=1.[O-:54][S:55]([O-:58])(=S)=O.[Na+].[Na+]>ClCCl.O>[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:42])[C@H:8]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([C:22]4[N:23]=[C:24]([S:55]([CH3:43])(=[O:58])=[O:54])[N:25]5[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=45)[N:20]=3)[N:15]([CH2:34][O:35][CH2:36][CH2:37][Si:38]([CH3:39])([CH3:41])[CH3:40])[CH:14]=2)=[O:12])[CH3:9])[CH2:4]1)#[N:2]

Participants

6

Reactant 3

HCID 24477Sodium ThiosulfateHCID 70297m-Chloroperbenzoic acid2×HCID 712888582-(6-fluoro-3-methylsulfanyl-imidazo[1,5-a]pyridin-1-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide

Product 1

HCID 712888502-(6-fluoro-3-methanesulfonyl-imidazo[1,5-a]pyridin-1-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amideYield 25%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

In a round-bottomed flask, 2-(6-fluoro-3-methylsulfanyl-imidazo[1,5-a]pyridin-1-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide (105 mg, 0.155 mmol) was dissolved in dichloromethane (4 ml). The solution was cooled to 0° C. and m-CPBA (75%, 79 mg, 0.343 mmol) was added. The ice bath was removed and the reaction mixture was stirred at room temperature overnight. Additional m-CPBA (75%, 36 mg, 0.155 mmol) was added and the reaction mixture was stirred at room temperature for 30 min. A solution of 10% aqueous Na2S2O3 (3 ml) was added and the biphasic mixture was stirred at room temperature for 1 h. The reaction mixture was diluted with water and extracted with dichloromethane. The organic layer was washed with saturated aqueous NaHCO3. The aqueous layer was extracted dichloromethane (2×). The combined organic layers were dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over silica gel with MeOH/CH2Cl2/0.5% NH4OH (gradient 0-2.5% MeOH) to afford 25 mg (25%) of 2-(6-fluoro-3-methanesulfonyl-imidazo[1,5-a]pyridin-1-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide as a light brown oil.

Workup

  1. customThe ice bath was removed
  2. stirringthe reaction mixture was stirred at room temperature for 30 min
  3. stirringthe biphasic mixture was stirred at room temperature for 1 h
  4. extractionextracted with dichloromethane
  5. washThe organic layer was washed with saturated aqueous NaHCO3
  6. extractionThe aqueous layer was extracted dichloromethane (2×)
  7. dry with materialThe combined organic layers were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was chromatographed over silica gel with MeOH/CH2Cl2/0.5% NH4OH (gradient 0-2.5% MeOH)

Sources & evidence

ORD record
ord-50d528cf88ce4025b0e707558bd0c982
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

Loading…