Hydrochloric Acid → HCID 86641323, compound

HRID 1693284Notes

Reaction equation

HRID 1693284 reaction equation
[CH3:1][S:2](Cl)(=O)=O.ClC1N=C(N(C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)[N:10]=[C:9]2[N:28]([CH2:36][C:37]3[C:42]([CH3:43])=[C:41]([O:44][CH3:45])[C:40]([CH3:46])=[CH:39][N:38]=3)[N:29]=[C:30]([CH2:31][CH:32]([OH:35])[CH2:33]O)[C:8]=12.ClC1N=[C:52]([N:54]([C:62]([O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[O:63])[C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])[N:51]=C2N(CC3C(C)=C(OC)C(C)=CN=3)N=C(CCC=O)C=12.N1C(C)=CC(C)=CC=1C.Cl>ClCCl>[OH:35][CH:32]1[C:33]2[CH2:1][S:2][N:51]=[C:52]([N:54]([C:62]([O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[O:63])[C:55]([O:57][C:58]([CH3:60])([CH3:61])[CH3:59])=[O:56])[C:9]3=[N:10][N:28]([CH2:36][C:37]4[C:42]([CH3:43])=[C:41]([O:44][CH3:45])[C:40]([CH3:46])=[CH:39][N:38]=4)[N:29]=[C:30]([C:8]=23)[CH2:31]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 79532,4,6-TrimethylpyridineHCID 31297Methanesulfonyl chlorideHCID 59311461HCID 59311461, compoundHCID 59311520HCID 59311520, compound

Product 1

HCID 86641323HCID 86641323, compoundYield 92%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
50 °C

Procedure

A solution of methanesulfonyl chloride (73 μL) in dehydrated dichloromethane was added dropwise to a mixture composed of di-tert-butyl {4-chloro-3-(2,3-dihydroxypropyl)-1-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}imidodicarbonate of Step 7) of Example 1 (510 mg), 2,4,6-collidine (1.15 mL) and dehydrated dichloromethane (17 mL) under cooling in an ice bath, and then the mixture was stirred for 15 hours. 0.5 N hydrochloric acid was added to the reaction mixture, followed by extraction with chloroform. The organic layer was washed with water, and then dried over anhydrous sodium sulfate and filtered. Then, the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in N,N-dimethylformamide (10 mL). Sodium bisulfide monohydrate (76 mg) was added under cooling in an ice bath, followed by stirring for 20 minutes. Potassium carbonate (142 mg) was added to the reaction mixture and the ice bath was removed. The mixture was stirred for one hour, and then heated to 50° C. and further heated with stirring for two hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was sequentially washed with water and 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 (453 mg, 92%) as an oil.

Workup

  1. temperatureunder cooling in an ice bath
  2. extractionfollowed by extraction with chloroform
  3. washThe organic layer was washed with water
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationThen, the filtrate was concentrated under reduced pressure
  7. dissolutionThe resulting residue was dissolved in N,N-dimethylformamide (10 mL)
  8. additionSodium bisulfide monohydrate (76 mg) was added
  9. temperatureunder cooling in an ice bath
  10. stirringby stirring for 20 minutes
  11. additionPotassium carbonate (142 mg) was added to the reaction mixture
  12. customthe ice bath was removed
  13. stirringThe mixture was stirred for one hour
  14. temperaturefurther heated
  15. stirringwith stirring for two hours
  16. additionWater was added to the reaction mixture
  17. extractionfollowed by extraction with ethyl acetate
  18. washThe organic layer was sequentially washed with water and brine
  19. dry with materialdried over anhydrous sodium sulfate
  20. filtrationAfter filtration
  21. concentrationthe filtrate was concentrated under reduced pressure
  22. customThe resulting residue was purified by silica gel column chromatography (ethyl acetate-hexane)

Sources & evidence

ORD record
ord-29251e0fe1e6422ab6b56b5c7facd93c
Source dataset
uspto-grants-2012_04
Patent number
US08158638B2

Reaction notes

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