Trifluoroacetic acid → HCID 22591478, compound

HRID 22783Notes

Reaction equation

HRID 22783 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][O:16][C:17]2[CH:26]=[C:25]3[C:20]([C:21]([NH:27][C:28]4[C:36]5[O:35][CH:34]=[CH:33][C:32]=5[CH:31]=[CH:30][C:29]=4[Cl:37])=[N:22][CH:23]=[N:24]3)=[CH:19][C:18]=2[O:38][CH3:39])[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[Cl:37][C:29]1[CH:30]=[CH:31][C:32]2[CH:33]=[CH:34][O:35][C:36]=2[C:28]=1[NH:27][C:21]1[C:20]2[C:25](=[CH:26][C:17]([O:16][CH2:15][CH2:14][CH:11]3[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]3)=[C:18]([O:38][CH3:39])[CH:19]=2)[N:24]=[CH:23][N:22]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 22591462HCID 22591462, compound

Product 1

HCID 22591478HCID 22591478, compoundYield 73.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 7-[2-(N-tert-butoxycarbonylpiperidin-4-yl)ethoxy]-4-(6-chlorobenzofuran-7-ylamino)-6-methoxyquinazoline (0.49 g), trifluoroacetic acid (4 ml) and methylene chloride (15 ml) was stirred at ambient temperature for 3 hours. The solvents were evaporated and the residue was diluted with toluene and evaporated again. The residue was partitioned between a mixture of methylene chloride and acetonitrile and a 2N aqueous sodium hydroxide solution. The organic phase was washed with water and with brine, dried over magnesium sulphate and evaporated. The material so obtained was purified by column chromatography using increasingly polar mixtures of methylene chloride and a saturated methanolic ammonia solution. The material so obtained was triturated under diethyl ether to give the title compound (0.296 g); NMR Spectrum: (DMSOd6 and CF3CO2D) 1.4 (m, 2H), 1.75-1.95 (m, 5H), 2.9 (m, 2H), 3.3 (m, 2H), 4.05 (s, 3H), 4.3 (m, 2H), 7.15 (d, 1H), 7.4 (s, 1H), 7.55 (d, 1H), 7.8 (d, 1H), 8.1 (d, 1H), 8.2 (s, 1H), 8.8 (s, 1H), Mass Spectrum: M+H+ 453.

Workup

  1. customThe solvents were evaporated
  2. additionthe residue was diluted with toluene
  3. customevaporated again
  4. customThe residue was partitioned between a mixture of methylene chloride and acetonitrile
  5. washThe organic phase was washed with water and with brine
  6. dry with materialdried over magnesium sulphate
  7. customevaporated
  8. customThe material so obtained
  9. customwas purified by column chromatography
  10. temperatureusing increasingly polar mixtures of methylene chloride
  11. customThe material so obtained
  12. customwas triturated under diethyl ether

Sources & evidence

ORD record
ord-33e6091a997a4238b098bd7492a9fadf
Source dataset
uspto-grants-2005_02
Patent number
US06849625B2

Reaction notes

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