HCID 22030770, compound → HCID 135763126, compound

HRID 2084023Notes

Reaction equation

HRID 2084023 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-2f29a1de988d48aca1fd448e1a6ef1bb
Source dataset
uspto-grants-2004_04
Patent number
US06716847B2

Reaction notes

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