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 2171868Notes

Reaction equation

HRID 2171868 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-694b6af710d14d90a58de83a485f9e3b
Source dataset
uspto-grants-2015_06
Patent number
US09051319B2

Reaction notes

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