Trifluoroacetic acid → 6-Methoxy-4-(2-methylindol-5-yloxy)-7-(piperidin-4-ylmethoxy)quinazoline

HRID 1791603Notes

Reaction equation

HRID 1791603 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH:15]1[CH2:20][CH2:19][N:18](C(OC(C)(C)C)=O)[CH2:17][CH2:16]1)[N:9]=[CH:8][N:7]=[C:6]2[O:28][C:29]1[CH:30]=[C:31]2[C:35](=[CH:36][CH:37]=1)[NH:34][C:33]([CH3:38])=[CH:32]2.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1)[N:9]=[CH:8][N:7]=[C:6]2[O:28][C:29]1[CH:30]=[C:31]2[C:35](=[CH:36][CH:37]=1)[NH:34][C:33]([CH3:38])=[CH:32]2

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 220308476-Methoxy-4(2-methylindol-5-yloxy)-7-(1-tert-butoxycarbonylpiperidin-4-ylmethoxy)quinazoline

Product 1

HCID 220308736-Methoxy-4-(2-methylindol-5-yloxy)-7-(piperidin-4-ylmethoxy)quinazolineYield 96%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 6-methoxy-4-(2-methylindol-5-yloxy)-7-(1-tert-butoxycarbonylpiperidin-4-ylmethoxy)quinazoline (155 mg, 0.3 mmol), (prepared as described in Example 69), in methylene chloride (5 ml) containing TFA (1 ml) was stirred at ambient temperature for 30 minutes. The volatiles were removed under vacuum and the residue was treated with water and adjusted to pH12 with 2M sodium hydroxide. The mixture was extracted with methylene chloride. The organic layer was dried (MgSO4), and the volatiles were removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/ethyl acetate/methanol (5/4/1) followed by methylene chloride/methanol (9/1) and by 3M ammonia in methanol/methanol/methylene chloride (5/15/80). After removal of the solvent by evaporation, the residue was dissolved in the minimum of methylene chloride, ether was added followed by petroleum ether. The precipitate was collected by filtration, washed with ether and dried under vacuum to give 6-methoxy-4-(2-methylindol-5yloxy)-7-(piperidin-4-ylmethoxy)quinazoline (120 mg, 96%).

Workup

  1. customThe volatiles were removed under vacuum
  2. additionthe residue was treated with water
  3. extractionThe mixture was extracted with methylene chloride
  4. dry with materialThe organic layer was dried (MgSO4)
  5. customthe volatiles were removed by evaporation
  6. customThe residue was purified by column chromatography
  7. washeluting with methylene chloride/ethyl acetate/methanol (5/4/1)
  8. customAfter removal of the solvent
  9. customby evaporation
  10. dissolutionthe residue was dissolved in the minimum of methylene chloride, ether
  11. additionwas added
  12. filtrationThe precipitate was collected by filtration
  13. washwashed with ether
  14. customdried under vacuum

Sources & evidence

ORD record
ord-217d5f891d1e4cc6b69362dc24ec7253
Source dataset
uspto-grants-2006_07
Patent number
US07074800B1

Reaction notes

Loading…