7-(1-Tert-butoxycarbonylpiperidin-4-ylmethoxy)-4-(2-methylindol-5-yloxy)quinazoline → 4-(2-Methylindol-5-yloxy)-7-(piperidin-4-ylmethoxy)quinazoline

HRID 454099Notes

Reaction equation

HRID 454099 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][O:15][C:16]2[CH:25]=[C:24]3[C:19]([C:20]([O:26][C:27]4[CH:28]=[C:29]5[C:33](=[CH:34][CH:35]=4)[NH:32][C:31]([CH3:36])=[CH:30]5)=[N:21][CH:22]=[N:23]3)=[CH:18][CH:17]=2)[CH2:10][CH2:9]1)=O)(C)(C)C>C(Cl)Cl.C(O)(C(F)(F)F)=O>[CH3:36][C:31]1[NH:32][C:33]2[C:29]([CH:30]=1)=[CH:28][C:27]([O:26][C:20]1[C:19]3[C:24](=[CH:25][C:16]([O:15][CH2:14][CH:11]4[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]4)=[CH:17][CH:18]=3)[N:23]=[CH:22][N:21]=1)=[CH:35][CH:34]=2

Participants

4

Reactant 1

HCID 220308467-(1-Tert-butoxycarbonylpiperidin-4-ylmethoxy)-4-(2-methylindol-5-yloxy)quinazoline

Product 1

HCID 220308754-(2-Methylindol-5-yloxy)-7-(piperidin-4-ylmethoxy)quinazolineYield 67%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A suspension of 7-(1-tert-butoxycarbonylpiperidin-4-ylmethoxy)-4-(2-methylindol-5-yloxy)quinazoline (150 mg, 0.31 mmol), (prepared as described in Example 90), in methylene chloride (2 ml) and TFA (1.5 ml) was stirred for 1 hour at ambient temperature. After removal of the volatiles under vacuum the residue was azeotroped with toluene. The residue was partitioned between methylene chloride and water and the aqueous layer was adjusted to pH11. The organic layer was separated, washed with brine, dried (MgSO4), and evaporated. The residue was triturated with ether, filtered, washed with ether and dried under vacuum to give 4-(2-methylindol-5-yloxy)-7-(piperidin-4-ylmethoxy)quinazoline (80 mg, 67%).

Workup

  1. customAfter removal of the volatiles under vacuum the residue
  2. customwas azeotroped with toluene
  3. customThe residue was partitioned between methylene chloride and water
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried (MgSO4)
  7. customevaporated
  8. customThe residue was triturated with ether
  9. filtrationfiltered
  10. washwashed with ether
  11. customdried under vacuum

Sources & evidence

ORD record
ord-7d2401f006ec44538bdc6636ec644933
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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