Sodium Methoxide → (R)-3-(2-(5-Chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-ylamino)-4,4-dimethylpentanoic acid

HRID 1055035Notes

Reaction equation

HRID 1055035 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][C@@H:18]([C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:19][C:20]([OH:22])=[O:21])[C:14]([F:27])=[CH:13][N:12]=3)=[CH:9][N:8](S(C3C=CC(C)=CC=3)(=O)=O)[C:5]2=[N:6][CH:7]=1.C[O-].[Na+]>CO>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][C@@H:18]([C:23]([CH3:25])([CH3:24])[CH3:26])[CH2:19][C:20]([OH:22])=[O:21])[C:14]([F:27])=[CH:13][N:12]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 10942334Sodium MethoxideHCID 71251334(R)-3-(2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-pyrimidin-4-ylamino)-4,4-dimethylpentanoic acid2×

Product 1

HCID 71251343(R)-3-(2-(5-Chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-ylamino)-4,4-dimethylpentanoic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a cold (0° C.) solution of (R)-3-(2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-pyrimidin-4-ylamino)-4,4-dimethylpentanoic acid, 3a, (0.08 g, 0.14 mmol) in MeOH (2.6 mL) was added sodium methanolate (2.91 mL of 25% w/v, 13.46 mmol). The reaction was stirred at room temperature for 30 min and then quenched by dilution into aqueous saturated ammonium chloride solution. The MeOH was evaporated in vacuo and the resulting aqueous phase diluted with EtOAc, then extracted with EtOAc (3×). The organics were dried (Na2SO4), filtered and concentrated in vacuo. Recrystalization from MeOH provided 52 mg of the desired product 1 as a white powder: 1H NMR (d6-DMSO) δ 12.25 (s, 1H): 12.0 (bs, 1H): 8.8 (s, 1H): 8.3 (s, 1H): 8.25 (s, 1H); 8.1 (s, 1H): 7.45 (d, 1H); 4.75 (t, 1H); 2.5 (m, 2H), 1.0 (s, 9H); LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, RT=2.06 minutes (M+H) 392.21.

Workup

  1. customquenched by dilution into aqueous saturated ammonium chloride solution
  2. customThe MeOH was evaporated in vacuo
  3. additionthe resulting aqueous phase diluted with EtOAc
  4. extractionextracted with EtOAc (3×)
  5. dry with materialThe organics were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customRecrystalization from MeOH

Sources & evidence

ORD record
ord-16d96042d9d942c5a00eafcf7424689e
Source dataset
uspto-grants-2016_07
Patent number
US09394302B2

Reaction notes

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