Hydrochloric Acid → HCID 59309757, compound

HRID 1513089Notes

Reaction equation

HRID 1513089 reaction equation
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][C:7](=[O:32])[N:8]2[C:11]2[CH:16]=[C:15]([O:17][CH2:18][C:19]3[C:24]([O:25][CH3:26])=[CH:23][CH:22]=[C:21]([F:27])[C:20]=3[F:28])[C:14]([O:29][CH3:30])=[CH:13][C:12]=2[Cl:31])=[C:4]([O:33][CH3:34])[N:3]=1.C(N(CC)C(C)C)(C)C.C([O:47][CH2:48][C:49](Cl)=[O:50])(=O)C.Cl>C(OCC)(=O)C>[Cl:31][C:12]1[CH:13]=[C:14]([O:29][CH3:30])[C:15]([O:17][CH2:18][C:19]2[C:24]([O:25][CH3:26])=[CH:23][CH:22]=[C:21]([F:27])[C:20]=2[F:28])=[CH:16][C:11]=1[N:8]1[C:7](=[O:32])[NH:6][C:5]2[C:9]1=[N:10][C:2]([NH:1][C:48](=[O:47])[CH2:49][OH:50])=[N:3][C:4]=2[O:33][CH3:34]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 26297Acetoxyacetyl chlorideHCID 81531DiisopropylethylamineHCID 59310119HCID 59310119, compound

Product 1

HCID 59309757HCID 59309757, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 2-amino-9-[2-chloro-5-(2,3-difluoro-6-methoxybenzyloxy)-4-methoxyphenyl]-6-methoxy-7,9-dihydro-8H-purin-8-one (40 mg) and N,N-diisopropyl-ethylamine (0.15 mL) in ethyl acetate (4 mL) was added acetoxyacetyl chloride (0.078 mL), and the mixture was stirred at room temperature overnight. To the reaction mixture was added 1 mol/L hydrochloric acid, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was dissolved in methanol (1 mL)-tetrahydrofuran (2 mL). To the solution was added sodium methoxide (28% methanol solution, 0.05 mL), and the mixture was stirred at room temperature for 1 hour. To the reaction mixture was added 1 mol/L hydrochloric acid, and the mixture was poured into a saturated aqueous ammonium chloride solution, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=1/1−ethyl acetate) to give the title compound (4 mg).

Workup

  1. extractionthe resulting mixture was extracted with ethyl acetate
  2. washThe extract was washed with water and brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was removed under reduced pressure
  5. dissolutionthe residue was dissolved in methanol (1 mL)-tetrahydrofuran (2 mL)
  6. additionTo the solution was added sodium methoxide (28% methanol solution, 0.05 mL)
  7. stirringthe mixture was stirred at room temperature for 1 hour
  8. additionTo the reaction mixture was added 1 mol/L hydrochloric acid
  9. additionthe mixture was poured into a saturated aqueous ammonium chloride solution
  10. extractionthe resulting mixture was extracted with ethyl acetate
  11. washThe extract was washed with water and brine
  12. dry with materialdried over anhydrous sodium sulfate
  13. customThe solvent was removed under reduced pressure
  14. customthe residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=1/1−ethyl acetate)

Sources & evidence

ORD record
ord-6a5d0e0d3ccb477c9e7dede59024e1c1
Source dataset
uspto-grants-2012_07
Patent number
US08217069B2

Reaction notes

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