Potassium Carbonate → HCID 22140854, compound

HRID 641767Notes

Reaction equation

HRID 641767 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:24]=[C:23](O)[CH:22]=[C:21]3[C:16]=2[C:17]([NH:26][C:27]2[C:32]([Cl:33])=[CH:31][CH:30]=[C:29]4[O:34][CH2:35][O:36][C:28]=24)=[N:18][CH:19]=[N:20]3)[CH2:10][CH2:9]1)=O)(C)(C)C.C1(C)C=CC(S([O:46][CH2:47][C:48]([F:51])([F:50])[F:49])(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Cl:33][C:32]1[C:27]([NH:26][C:17]2[C:16]3[C:21](=[CH:22][C:23]([O:46][CH2:47][C:48]([F:51])([F:50])[F:49])=[CH:24][C:15]=3[O:14][CH:11]3[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]3)[N:20]=[CH:19][N:18]=2)=[C:28]2[O:36][CH2:35][O:34][C:29]2=[CH:30][CH:31]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 67942Ethanol, 2,2,2-trifluoro-, 1-(4-methylbenzenesulfonate)HCID 135510703HCID 135510703, compound

Product 1

HCID 22140854HCID 22140854, compoundYield 42.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 5-[N-(tert-butoxycarbonyl)piperidin-4-yloxy]-4-(6-chloro-2,3-methylenedioxyanilino)-7-hydroxyquinazoline (0.15 g), 2,2,2-trifluoroethyl 4-toluenesulphonate (0.089 g), potassium carbonate (0.1 g) and DMF (3 ml) was stirred and heated to 95° C. for 24 hours. The mixture was cooled to ambient temperature and partitioned between ethyl acetate and water. The organic solution was washed with 1N aqueous sodium hydroxide solution and with brine and dried over magnesium sulphate. The organic solution was filtered and a 6N solution of hydrogen chloride in diethyl ether (2 ml) was added. The mixture was stirred at ambient temperature for 16 hours. The mixture was evaporated. The residue was dissolved in methylene chloride (3 ml) and a saturated methanolic ammonia solution (1 ml) was added. The mixture was filtered and the filtrate was evaporated. The residue was purified by column chromatography on silica using a 19:1 mixture of methylene chloride and a saturated methanolic ammonia solution as eluent. There was thus obtained the title compound (0.061 g); NMR Spectrum: (CDCl3) 1.85-2.0 (m, 2H), 2.3 (m, 2H), 2.8-2.95 (m, 2H), 3.1-3.3 (m, 2H), 4.5 (m, 2H), 4.72 (m, 1H), 6.08 (s, 2H), 6.6 (d, 1H), 6.75 (d, 1H), 6.82 (d, 1H), 7.0 (d, 1H), 8.58 (s, 1H), 9.32 (s, 1H); Mass Spectrum: M+H+ 497 and 499.

Workup

  1. temperatureThe mixture was cooled to ambient temperature
  2. custompartitioned between ethyl acetate and water
  3. washThe organic solution was washed with 1N aqueous sodium hydroxide solution and with brine
  4. dry with materialdried over magnesium sulphate
  5. filtrationThe organic solution was filtered
  6. additiona 6N solution of hydrogen chloride in diethyl ether (2 ml) was added
  7. stirringThe mixture was stirred at ambient temperature for 16 hours
  8. customThe mixture was evaporated
  9. dissolutionThe residue was dissolved in methylene chloride (3 ml)
  10. additiona saturated methanolic ammonia solution (1 ml) was added
  11. filtrationThe mixture was filtered
  12. customthe filtrate was evaporated
  13. customThe residue was purified by column chromatography on silica using
  14. additiona 19:1 mixture of methylene chloride

Sources & evidence

ORD record
ord-f97891d173d74797abfa7150bb976a09
Source dataset
uspto-grants-2010_04
Patent number
US07696214B2

Reaction notes

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