Triethylamine → HCID 59311451, compound

HRID 1693323Notes

Reaction equation

HRID 1693323 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[N:5]=[C:4]2[N:23]([CH2:29][C:30]3[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=3)[N:24]=[C:25]([CH2:26][CH2:27]O)[C:3]=12.C(N(CC)CC)C.C[S:46](Cl)(=O)=O>ClCCl.C(OCC)(=O)C>[CH3:37][O:36][C:33]1[CH:34]=[CH:35][C:30]([CH2:29][N:23]2[C:4]3[C:3]4[C:25]([CH2:26][CH2:27][S:46][C:2]=4[N:7]=[C:6]([N:8]([C:9]([O:11][C:12]([CH3:13])([CH3:15])[CH3:14])=[O:10])[C:16]([O:18][C:19]([CH3:21])([CH3:22])[CH3:20])=[O:17])[N:5]=3)=[N:24]2)=[CH:31][CH:32]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 59311386HCID 59311386, compound

Product 1

HCID 59311451HCID 59311451, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

The above di-tert-butyl {4-chloro-3-(2-hydroxyethyl)-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl}imidodicarbonate (8.5 g) was dissolved in dichloromethane (100 ml), triethylamine (4.5 ml) was added. Methanesulfonyl chloride (1.9 ml) was added under cooling in an ice bath, and the mixture was stirred at room temperature for two hours. The reaction solution was diluted with dichloromethane and ethyl acetate and washed with water. Then, the organic layer was dried over anhydrous sodium sulfate and filtered, and then the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in N,N-dimethylformamide (100 mL), and sodium bisulfide monohydrate (1.5 g) was added under cooling in an ice bath. Then, the ice bath was removed and the mixture was stirred for one hour. Potassium carbonate (3.3 g) was added to the reaction mixture, followed by further stirring for 16 hours. Water (1000 ml) was added to the reaction mixture, followed by extraction with dichloromethane (500 ml) twice. The organic layer was washed with brine, and then dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate-hexane) to obtain the title compound (6.0 g, 74%) as an oil.

Workup

  1. temperatureunder cooling in an ice bath
  2. washwashed with water
  3. dry with materialThen, the organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. dissolutionThe resulting residue was dissolved in N,N-dimethylformamide (100 mL)
  7. additionsodium bisulfide monohydrate (1.5 g) was added
  8. temperatureunder cooling in an ice bath
  9. customThen, the ice bath was removed
  10. stirringthe mixture was stirred for one hour
  11. additionPotassium carbonate (3.3 g) was added to the reaction mixture
  12. stirringby further stirring for 16 hours
  13. additionWater (1000 ml) was added to the reaction mixture
  14. extractionfollowed by extraction with dichloromethane (500 ml) twice
  15. washThe organic layer was washed with brine
  16. dry with materialdried over anhydrous sodium sulfate
  17. filtrationAfter filtration
  18. concentrationthe filtrate was concentrated under reduced pressure
  19. customThe resulting residue was purified by silica gel column chromatography (ethyl acetate-hexane)

Sources & evidence

ORD record
ord-4f6f0b12af654e899fbabc47364fbd81
Source dataset
uspto-grants-2012_04
Patent number
US08158638B2

Reaction notes

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