Tetrahydrofuran → 5-{2-[2-(tert-butylthio)ethoxy]ethyl}-N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidin-4-amine

HRID 1926087Notes

Reaction equation

HRID 1926087 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:19][C:20]2[C:21]3[N:28]([CH2:29][CH2:30][O:31][CH2:32]CO)[CH:27]=[CH:26][C:22]=3[N:23]=[CH:24][N:25]=2)[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=1.[CH2:35](N(CC)CC)C.[CH3:42][S:43](Cl)(=O)=O.C(=O)([O-])O.[Na+].O1[CH2:56][CH2:55][CH2:54]C1>>[C:55]([S:43][CH2:42][CH2:32][O:31][CH2:30][CH2:29][N:28]1[C:21]2[C:20]([NH:19][C:4]3[CH:5]=[CH:6][C:7]([O:8][C:9]4[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:16])([F:18])[F:17])[CH:10]=4)=[C:2]([Cl:1])[CH:3]=3)=[N:25][CH:24]=[N:23][C:22]=2[CH:26]=[CH:27]1)([CH3:54])([CH3:56])[CH3:35]

Participants

6

Reactant 5

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 116846292-(2-(4-((3-chloro-4-(3-(trifluoromethyl)phenoxy)phenyl)amino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl)ethoxy)ethan-1-ol

Product 1

HCID 675211475-{2-[2-(tert-butylthio)ethoxy]ethyl}-N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidin-4-amine

Procedure

2-{2-[4-({3-Chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl]ethoxy}ethanol (150 mg) was dissolved in tetrahydrofuran (6.0 mL), and triethylamine (1.00 mL) and methanesulfonyl chloride (0.59 mL) were added under ice-cooling and the mixture was stirred for 1 hr. Saturated aqueous sodium hydrogen carbonate was added to this reaction solution under ice-cooling and the mixture was extracted with ethyl acetate. The extract was dried over magnesium sulfate and concentrated, and the residue was dissolved in a mixed solvent of N,N-dimethylformamide (4.0 mL) and tetrahydrofuran (6.0 mL). Sodium 2-methylpropane-2-thiolate (220 mg) was added, and the mixture was stirred at room temperature for 1 hr. Saturated aqueous sodium hydrogen carbonate was added to the reaction mixture under ice-cooling and the mixture was extracted with ethyl acetate. The extract was dried over magnesium sulfate and concentrated. The residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate:methanol=100:0→ethyl acetate:methanol=90:10) to give the title compound (143 mg).

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. extractionthe mixture was extracted with ethyl acetate
  4. dry with materialThe extract was dried over magnesium sulfate
  5. concentrationconcentrated
  6. dissolutionthe residue was dissolved in a mixed solvent of N,N-dimethylformamide (4.0 mL) and tetrahydrofuran (6.0 mL)
  7. additionSodium 2-methylpropane-2-thiolate (220 mg) was added
  8. stirringthe mixture was stirred at room temperature for 1 hr
  9. additionSaturated aqueous sodium hydrogen carbonate was added to the reaction mixture under ice-
  10. temperaturecooling
  11. extractionthe mixture was extracted with ethyl acetate
  12. dry with materialThe extract was dried over magnesium sulfate
  13. concentrationconcentrated
  14. customThe residue was separated
  15. custompurified by silica gel column chromatography (eluent, ethyl acetate:methanol=100:0→ethyl acetate:methanol=90:10)

Sources & evidence

ORD record
ord-65f95c70f45b465c9e927bc573e488a2
Source dataset
uspto-grants-2012_05
Patent number
US08178543B2

Reaction notes

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