Tetrahydrofuran → HCID 67338993, compound

HRID 2092302Notes

Reaction equation

HRID 2092302 reaction equation
[CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[C:8]([NH:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15](SC)[CH:14]=3)=[N:7][CH:6]=[CH:5][C:4]=2[C:3]=1[NH:21][C:22]1[C:27]([C:28]2[CH:33]=[CH:32][N:31]=[CH:30][N:29]=2)=[CH:26][CH:25]=[CH:24][N:23]=1.O[O:35][S:36]([O-:38])=O.[K+].[CH2:40]1COCC1>CO.O>[CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[C:8]([NH:12][C:13]3[CH:14]=[CH:15][CH:16]=[C:17]([S:36]([CH3:40])(=[O:38])=[O:35])[CH:18]=3)=[N:7][CH:6]=[CH:5][C:4]=2[C:3]=1[NH:21][C:22]1[C:27]([C:28]2[CH:33]=[CH:32][N:31]=[CH:30][N:29]=2)=[CH:26][CH:25]=[CH:24][N:23]=1

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 23707502Potassium hydroxy sulfiteHCID 67339043HCID 67339043, compound

Product 1

HCID 67338993HCID 67338993, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 6-methyl-N1-(3-(methylthio)phenyl)-N5-(3-(pyrimidin-4-yl)pyridin-2-yl)isoquinoline-1,5-diamine (0.250 g, 0.555 mmol) in THF (30 mL) and MeOH (20 mL) was stirred in an ice bath and treated with a solution of oxone® (0.750 g, 1.22 mmol) in water (10 mL). The resulting cloudy reaction mixture was stirred at 0° C. (warming slowly to ˜10° C.) for 3 h. The reaction mixture was quenched at 0° C. by the addition of satd aq Na2SO3 (100 mL) and stirred at that temperature for 15 min. The mixture was concentrated in vacuo to remove THF and the remaining aqueous mixture was extracted with 3:1 CHCl3:IPA (3×100 mL). The organic extract was washed with saturated aqueous NaCl (50 mL), dried over Na2SO4, filtered, and concentrated in vacuo to afford a yellow solid. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep® pre-packed silica gel column (40 g), eluting with a gradient of 1% to 8% MeOH in CH2Cl2, to provide 6-methyl-N1-(3-(methylsulfonyl)phenyl)-N5-(3-(pyrimidin-4-yl)pyridin-2-yl)isoquinoline-1,5-diamine. MS (M+H)+ 483.5.

Workup

  1. customThe resulting cloudy reaction mixture
  2. temperaturewarming slowly to ˜10° C.) for 3 h
  3. customThe reaction mixture was quenched at 0° C. by the addition of satd aq Na2SO3 (100 mL)
  4. stirringstirred at that temperature for 15 min
  5. concentrationThe mixture was concentrated in vacuo
  6. customto remove THF
  7. extractionthe remaining aqueous mixture was extracted with 3:1 CHCl3
  8. extractionThe organic extract
  9. washwas washed with saturated aqueous NaCl (50 mL)
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customto afford a yellow solid
  14. customchromatographed through a Redi-Sep® pre-packed silica gel column (40 g)
  15. washeluting with a gradient of 1% to 8% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-92b4bdc0cf2642ac9da58de410182a05
Source dataset
uspto-grants-2013_05
Patent number
US08440674B2

Reaction notes

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