Ammonium Chloride → 2-((S)-2-(5-fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-ylamino)-3,3-dimethylbutylsulfinyl)ethanoic acid

HRID 1055134Notes

Reaction equation

HRID 1055134 reaction equation
[F:1][C:2]1[C:3]([NH:28][CH:29]([C:41]([CH3:44])([CH3:43])[CH3:42])[CH2:30][S@@:31]([CH2:33][C:34]([O:36]C(C)(C)C)=[O:35])=[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.C[O-].[Na+].[NH4+].[Cl-]>C1COCC1>[F:1][C:2]1[C:3]([NH:28][CH:29]([C:41]([CH3:44])([CH3:43])[CH3:42])[CH2:30][S@@:31]([CH2:33][C:34]([OH:36])=[O:35])=[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 3

HCID 25517Ammonium ChlorideHCID 10942334Sodium MethoxideHCID 86714778tert-Butyl 2-((S)-2-(5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-ylamino)-3,3-dimethylbutylsulfinyl)ethanoate2×

Product 1

HCID 867147812-((S)-2-(5-fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-ylamino)-3,3-dimethylbutylsulfinyl)ethanoic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl 2-((S)-2-(5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-ylamino)-3,3-dimethylbutylsulfinyl)ethanoate, 176a, (0.42 g, 0.64 mmol) in THF (10 mL) was added NaOMe (0.21 mL of 25% solution in MeOH, 0.96 mmol). The solution was stirred at room temperature for 30 minutes. Aqueous saturated NH4Cl solution was added and the solvent was removed under reduced pressure. The residue was dissolved in water (20 mL) and the aqueous layer was extracted with EtOAc (3×20 mL). The combined organic phases were dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (0-15% MeOH/CH2Cl2 gradient) to afford 36 mg of the desired product as a white solid: 1H NMR (400 MHz, MeOD) δ 8.60-8.52 (m, 1H), 8.46 (s, 1H), 8.32 (d, J=5.3 Hz, 2H), 5.16 (m, 2H), 4.00 (d, J=14.7 Hz, 1H), 3.80 (d, J=14.7 Hz, 1H), 3.59 (d, J=13.9, 1H), 1.12 (s, 9H); LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, Retention Time=1.93 minutes (M+H) 438.25.

Workup

  1. customthe solvent was removed under reduced pressure
  2. dissolutionThe residue was dissolved in water (20 mL)
  3. extractionthe aqueous layer was extracted with EtOAc (3×20 mL)
  4. dry with materialThe combined organic phases were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel chromatography (0-15% MeOH/CH2Cl2 gradient)

Sources & evidence

ORD record
ord-0216a4966b2d48dda1214499d35a8f78
Source dataset
uspto-grants-2016_07
Patent number
US09394302B2

Reaction notes

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