Ammonium Chloride → (S)-N-(3,3-dimethyl-1-(methylsulfonyl)butan-2-yl)-5-fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-amine

HRID 1055073Notes

Reaction equation

HRID 1055073 reaction equation
[CH3:1][C:2]([CH3:38])([CH3:37])[C@H:3]([NH:9][C:10]1[C:15]([F:16])=[CH:14][N:13]=[C:12]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([F:26])[CH:24]=3)[N:19](S(C3C=CC(C)=CC=3)(=O)=O)[CH:18]=2)[N:11]=1)[CH2:4][S:5]([CH3:8])(=[O:7])=[O:6].C[O-].[Na+].[NH4+].[Cl-]>C1COCC1>[CH3:1][C:2]([CH3:38])([CH3:37])[C@H:3]([NH:9][C:10]1[C:15]([F:16])=[CH:14][N:13]=[C:12]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([F:26])[CH:24]=3)[NH:19][CH:18]=2)[N:11]=1)[CH2:4][S:5]([CH3:8])(=[O:7])=[O:6]

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 10942334Sodium MethoxideHCID 71247802(S)-N-(3,3-dimethyl-1-(methylsulfonyl)butan-2-yl)-5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-amine2×

Product 1

HCID 71251252(S)-N-(3,3-dimethyl-1-(methylsulfonyl)butan-2-yl)-5-fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-amine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)—N-(3,3-dimethyl-1-(methylsulfonyl)butan-2-yl)-5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-amine, 80a, (0.21 g, 0.37 mmol) in THF (10 mL) was added NaOMe (0.33 mL of 25% solution in MeOH, 1.45 mmol). The solution was stirred at room temperature for 10 minutes, then diluted into aqueous saturated NH4Cl solution. The solvent was removed under reduced pressure and the residue was dissolved in water (10 mL). The aqueous layer was extracted with EtOAc (3×10 mL), dried (MgSO4), filtered and concentrated in vacuo. The product was purified by silica gel chromatography (0-10% MeOH/CH2Cl2 gradient) to afford 109 mg of the desired product as a white solid: 1H NMR (400 MHz, CDCl3) δ 9.38 (s, 1H), 8.53 (d, J=6.9 Hz, 1H), 8.16 (m, 2H), 8.06 (s, 1H), 5.09-4.89 (m, 1H), 3.42-3.31 (m, 1H), 3.11 (m, 1H), 2.84 (s, 3H), 1.00 (s, 9H); LC/MS (10-90% ACN/water 5 min with 0.9% FA) m/z 410.19 (M+H) RT=2.03 minutes.

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionthe residue was dissolved in water (10 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (3×10 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe product was purified by silica gel chromatography (0-10% MeOH/CH2Cl2 gradient)

Sources & evidence

ORD record
ord-eb313cf9f15d49f4931156cc80b4c47a
Source dataset
uspto-grants-2016_07
Patent number
US09394302B2

Reaction notes

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