HCID 22030770, compound → HCID 135763126, compound

HRID 1357714Notes

Reaction equation

HRID 1357714 reaction equation
ClC1C=CC([O:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH2:20][CH:21]4[CH2:26][CH2:25][CH2:24][N:23]([CH3:27])[CH2:22]4)=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=C(F)C=1>Cl>[CH3:18][O:17][C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][C:13]=1[O:19][CH2:20][CH:21]1[CH2:26][CH2:25][CH2:24][N:23]([CH3:27])[CH2:22]1)[N:10]=[CH:9][NH:8][C:7]2=[O:6]

Participants

3

Reactant 1

HCID 22030770HCID 22030770, compound

Product 1

HCID 135763126HCID 135763126, compoundYield 66.8%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

4-(4-Chloro-2-fluorophenoxy)-6-methoxy-7-(N-methylpiperidin-3-ylmethoxy)quinazoline (8.7 g, 20 mmol) was dissolved in 2M aqueous hydrochloric acid (150 ml) and the mixture was stirred and heated to reflux for 1.5 hours. The reaction mixture was concentrated by evaporation under vacuum and the residue was basified to pH9 by the addition of saturated aqueous ammonium hydroxide solution. The aqueous layer was extracted with methylene chloride (4×400 ml). The combined organic extracts were filtered through phase-separating paper and evaporated. The solid so obtained was triturated under diethyl ether to give 6-methoxy-7-(N-methylpiperidin-3-ylmethoxy)-3,4-dihydroquinazolin-4-one (4.05 g, 66%) as a white solid; NMR: (DMSOd6) 1.05 (m, 1H), 1.40-1.95 (m, 5H), 2.02 (m, 1H), 2.14 (s, 3H), 2.59 (d, 1H), 2.78 (d, 1H), 3.85 (s, 3H), 3.95 (d, 2H), 7.09 (s, 1H), 7.42 (s, 1H), 7.95 (s, 1H), 12.0 (s, 1H); Mass: M+H+ 304.

Workup

  1. temperatureheated
  2. temperatureto reflux for 1.5 hours
  3. concentrationThe reaction mixture was concentrated by evaporation under vacuum
  4. additionthe residue was basified to pH9 by the addition of saturated aqueous ammonium hydroxide solution
  5. extractionThe aqueous layer was extracted with methylene chloride (4×400 ml)
  6. filtrationThe combined organic extracts were filtered
  7. customthrough phase-separating paper
  8. customevaporated
  9. customThe solid so obtained
  10. customwas triturated under diethyl ether

Sources & evidence

ORD record
ord-a61e3beb98cc4e48af1d8ccc0c475ac5
Source dataset
uspto-grants-2003_07
Patent number
US06593333B1

Reaction notes

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