Hydrochloric Acid → 4-[(4-fluoro-1H-indol-5-yl)oxy]-7-methoxy-6-(piperidin-4-ylmethoxy)quinazoline

HRID 916470Notes

Reaction equation

HRID 916470 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][O:15][C:16]2[CH:17]=[C:18]3[C:23](=[CH:24][C:25]=2[O:26][CH3:27])[N:22]=[CH:21][N:20]=[C:19]3[O:28][C:29]2[C:30]([F:38])=[C:31]3[C:35](=[CH:36][CH:37]=2)[NH:34][CH:33]=[CH:32]3)[CH2:10][CH2:9]1)=O)(C)(C)C.Cl>O1CCOCC1>[F:38][C:30]1[C:29]([O:28][C:19]2[C:18]3[C:23](=[CH:24][C:25]([O:26][CH3:27])=[C:16]([O:15][CH2:14][CH:11]4[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]4)[CH:17]=3)[N:22]=[CH:21][N:20]=2)=[CH:37][CH:36]=[C:35]2[C:31]=1[CH:32]=[CH:33][NH:34]2

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 670192356-[1-(tert-butoxycarbonyl)piperidin-4-yl]methoxy-4-[(4-fluoro-1H-indol-5-yl)oxy]-7-methoxyquinazoline

Product 1

HCID 589602244-[(4-fluoro-1H-indol-5-yl)oxy]-7-methoxy-6-(piperidin-4-ylmethoxy)quinazolineYield 86.9%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

6-[1-(tert-Butoxycarbonyl)piperidin-4-yl]methoxy-4-[(4-fluoro-1H-indol-5-yl)oxy]-7-methoxyquinazoline (306 mg containing 10% w/w triphenylphosphine oxide) was dissolved in 1,4-dioxane (5 ml) and 4M hydrogen chloride in 1,4-dioxane (5 ml) was added. The mixture was stirred at ambient temperature for 2.5 hours and then concentrated under reduced pressure. The residue was dissolved in methanol and adsorbed onto an Isolute SCX column, washed with methanol and then eluted with 7N ammonia in methanol to give 4-[(4-fluoro-1H-indol-5-yl)oxy]-7-methoxy-6-(piperidin-4-ylmethoxy)quinazoline (215 mg, 66% over two steps).

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe residue was dissolved in methanol
  3. washwashed with methanol
  4. washeluted with 7N ammonia in methanol

Sources & evidence

ORD record
ord-2813c21fbd9a4ae696c3ac30a05e8630
Source dataset
uspto-grants-2007_09
Patent number
US07268230B2

Reaction notes

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