Hydrochloric Acid → (R)-methyl 3-((5-fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)-4,4-dimethylpentanoate

HRID 1055039Notes

Reaction equation

HRID 1055039 reaction equation
[F:1][C:2]1[C:3]([NH:28][C@@H:29]([C:35]([CH3:38])([CH3:37])[CH3:36])[CH2:30][C:31]([O:33][CH3:34])=[O:32])=[N:4][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[C:14]([F:17])[CH:15]=3)[N:10](S(C3C=CC(C)=CC=3)(=O)=O)[CH:9]=2)=[N:6][CH:7]=1.Cl>C(#N)C.O1CCOCC1>[F:1][C:2]1[C:3]([NH:28][C@@H:29]([C:35]([CH3:38])([CH3:37])[CH3:36])[CH2:30][C:31]([O:33][CH3:34])=[O:32])=[N:4][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[C:14]([F:17])[CH:15]=3)[NH:10][CH:9]=2)=[N:6][CH:7]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 71247937(R)-methyl 3-((5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)-4,4-dimethylpentanoate2×

Product 1

HCID 71247865(R)-methyl 3-((5-fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)-4,4-dimethylpentanoate

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of (R)-methyl 3-((5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)-4,4-dimethylpentanoate, 8a, (21 g, 39 mmol) in acetonitrile (157 mL) was added 4M HCl in dioxane (174 mL). The reaction mixture was heated to 65° C. for 4 h. The solution was cooled to room temperature and the solvents were removed under reduced pressure. The mixture was flushed with acetonitrile after which dichloromethane (100 mL), sat. aqueous NaHCO3 (355 mL) and ethyl acetate (400 mL) were added. The phases were separated and the aqueous layer washed with ethyl acetate (500 mL). The organic layers were combined, dried (Na2SO4), filtered and concentrated in vacuo. The resulting residue was purified on silica gel (EtOAc/Hexanes) to provide the desired product, 9a, (12.1 g): LCMS Gradient 10-90%, 0.1% formic acid, 5 min, C18/ACN, RT=2.26 minutes (M+H) 391.05.

Workup

  1. temperatureThe solution was cooled to room temperature
  2. customthe solvents were removed under reduced pressure
  3. customThe mixture was flushed with acetonitrile after which dichloromethane (100 mL), sat. aqueous NaHCO3 (355 mL) and ethyl acetate (400 mL)
  4. additionwere added
  5. customThe phases were separated
  6. washthe aqueous layer washed with ethyl acetate (500 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe resulting residue was purified on silica gel (EtOAc/Hexanes)

Sources & evidence

ORD record
ord-4c71e7856fcc4ea6b1da766f2e9ddf1f
Source dataset
uspto-grants-2016_07
Patent number
US09394302B2

Reaction notes

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