Tetrahydrofuran → (2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-ylamino)-1-methylcyclohexanol

HRID 74942Notes

Reaction equation

HRID 74942 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]4C[CH2:22][CH2:21][C:20](C)(O)[CH2:19]4)[C:14]([F:26])=[CH:13][N:12]=3)=[CH:9][N:8]([S:27]([C:30]3[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=3)(=[O:29])=[O:28])[C:5]2=[N:6][CH:7]=1.[CH3:37][O-:38].[Na+].[CH2:40]1COCC1>CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][CH:18]4[CH2:19][CH2:20][CH2:21][CH2:22][C:37]4([CH3:40])[OH:38])[C:14]([F:26])=[CH:13][N:12]=3)=[CH:9][N:8]([S:27]([C:30]3[CH:31]=[CH:32][C:33]([CH3:36])=[CH:34][CH:35]=3)(=[O:29])=[O:28])[C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 10942334Sodium MethoxideHCID 68007207(3S)-3-(2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-ylamino)-1-methylcyclohexanol

Product 1

HCID 67285725(2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-ylamino)-1-methylcyclohexanol

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (3S)-3-[[2-[5-chloro-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridin-3-yl]-5-fluoro-pyrimidin-4-yl]amino]-1-methyl-cyclohexanol, 29f, (2.85 g, 5.38 mmol) in THF (200 mL) was added 1.5 ml 25% W/W sodium methoxide solution at room temperature. The reaction mixture was immediately injected into LC/MS. LC/MS indicated the reaction was complete. The reaction mixture was diluted with 200 ml EtOAc and the organic phase was washed twice with aqueous saturated NaHCO3 and then twice with brine. The organic phase was dried with MgSO4, filtered and concentrated in vacuo. The product was purified by silica gel chromatography (80 g silica, 5% MeOH/CH2Cl2) to afford 1.7 g of the desired product. The resulting product was dissolved in 70 ml THF, to it was added 1.8 ml 5M HCl/IPA. The resulting suspension was stirred for 1 hour at room temperature. The solvent was removed under reduced pressure to afford 1.7 g of the desired product, 655 as an HCl salt.

Workup

  1. washthe organic phase was washed twice with aqueous saturated NaHCO3
  2. dry with materialThe organic phase was dried with MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe product was purified by silica gel chromatography (80 g silica, 5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-e2fd84885bba48b98b3b8f3ec57182fc
Source dataset
uspto-grants-2014_09
Patent number
US08829007B2

Reaction notes

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