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

HRID 2068109Notes

Reaction equation

HRID 2068109 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-5ce5c3d2c56f4ff682067d170cc3c6f9
Source dataset
uspto-grants-2012_10
Patent number
US08293902B2

Reaction notes

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