Dimethyl Sulfoxide → HCID 136052274, compound

HRID 1889475Notes

Reaction equation

HRID 1889475 reaction equation
[Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].CS(C)=O.[Si]([O:20][CH2:21][C:22]1[N:23]([CH2:27][CH2:28][N:29]2[C:34](=[O:35])[C:33]3[CH:36]=[C:37]([CH2:39][CH3:40])[S:38][C:32]=3[N:31]([CH2:41][C:42]3[CH:47]=[CH:46][C:45]([C:48]4[C:49]([C:54]#[N:55])=[CH:50][CH:51]=[CH:52][CH:53]=4)=[CH:44][CH:43]=3)[C:30]2=[O:56])[CH:24]=[CH:25][N:26]=1)(C(C)(C)C)(C)C>C(Cl)(Cl)Cl.O1CCCC1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:39]([C:37]1[S:38][C:32]2[N:31]([CH2:41][C:42]3[CH:43]=[CH:44][C:45]([C:48]4[CH:53]=[CH:52][CH:51]=[CH:50][C:49]=4[C:54]4[NH:55][C:4](=[O:7])[O:5][N:3]=4)=[CH:46][CH:47]=3)[C:30](=[O:56])[N:29]([CH2:28][CH2:27][N:23]3[CH:24]=[CH:25][N:26]=[C:22]3[CH2:21][OH:20])[C:34](=[O:35])[C:33]=2[CH:36]=1)[CH3:40]

Participants

8

Reactant 4

HCID 679Dimethyl SulfoxideHCID 21645Hydroxylamine HClHCID 516892Sodium BicarbonateHCID 59351656HCID 59351656, compound

Product 1

HCID 136052274HCID 136052274, compoundYield 36%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of hydroxylammonium chloride (0.57 g), sodium hydrogencarbonate (0.82 g) and dimethyl sulfoxide (15 mL) was stirred at 40° C. for 30 min, 4′-{[3-{2-[2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-1H-imidazol-1-yl]ethyl}-6-ethyl-2,4-dioxo-3,4-dihydrothieno[2,3-d]pyrimidin-1(2H)-yl]methyl}biphenyl-2-carbonitrile (0.61 g) was added, and the mixture was stirred at 90° C. for 16 hr. The reaction mixture was diluted with chloroform, washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in methylene chloride (15 mL), N,N′-carbonyldiimidazole (0.18 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.16 mL) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with chloroform, washed successively with saturated aqueous potassium hydrogensulfate solution and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue obtained by silica gel column chromatography was dissolved in tetrahydrofuran (10 mL), tetrabutylammoniumbromide (1.0M tetrahydrofuran solution, 2.0 mL) was added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was extracted with 1N hydrochloric acid and chloroform, and the ethyl acetate layer was washed with saturated brine, and concentrated. The residue was purified by silica gel column chromatography to give the title compound as colorless crystals (0.2 g, 35%).

Workup

  1. stirringthe mixture was stirred at 90° C. for 16 hr
  2. washwashed successively with water and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. dissolutionThe residue was dissolved in methylene chloride (15 mL)
  6. additionN,N′-carbonyldiimidazole (0.18 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.16 mL) were added
  7. stirringthe mixture was stirred at room temperature for 2 hr
  8. additionThe reaction mixture was diluted with chloroform
  9. washwashed successively with saturated aqueous potassium hydrogensulfate solution and saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customThe solvent was evaporated under reduced pressure
  12. customThe residue obtained by silica gel column chromatography
  13. stirringthe mixture was stirred at room temperature for 2 hr
  14. extractionThe reaction mixture was extracted with 1N hydrochloric acid and chloroform
  15. washthe ethyl acetate layer was washed with saturated brine
  16. concentrationconcentrated
  17. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-45db208321de49838fa3c48a7ae61e6b
Source dataset
uspto-grants-2013_08
Patent number
US08501750B2

Reaction notes

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