Formamidine acetate → 4(1H)-Quinazolinone

HRID 454016Notes

Reaction equation

HRID 454016 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([O:10]CC)=O)=[CH:6][C:5](OC)=[C:4](OCC2CCN(C)CC2)[CH:3]=1.C(O)(=O)C.[CH:28](N)=[NH:29]>COCCO>[N:1]1[C:2]2[C:7](=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:8](=[O:10])[NH:29][CH:28]=1

Participants

4

Reactant 2

HCID 160693Formamidine acetate2×HCID 21874813Ethyl 2-amino-5-methoxy-4-((1-methylpiperidin-4-yl)methoxy)benzoate

Product 1

HCID 1354087534(1H)-QuinazolinoneYield 173.8%

Reagents, catalysts & solvents 1

HCID 80192-MethoxyethanolSolvent

Conditions

Temperature
115 °C

Procedure

A solution of ethyl 6-amino-3-methoxy-4-(1-methylpiperidin-4-ylmethoxy)benzoate (16.1 g, 50 mmol) in 2-methoxyethanol (160 ml) containing formamidine acetate (5.2 g, 50 mmol) was heated at 115° C. for 2 hours. Formamidine acetate (10.4 g, 100 mmol) was added in portions every 30 minutes during 4 hours. Heating was prolonged for 30 minutes after the last addition. After cooling, the volatiles were removed under vacuum. The solid was dissolved in ethanol (100 ml) and methylene chloride (50 ml). The precipitate was removed by filtration and the filtrate was concentrated to a final volume of 100 ml. The suspension was cooled to 5° C. and the solid was collected by filtration, washed with cold ethanol followed by ether and dried under vacuum overnight at 60° C. to give 6-methoxy-74(1-methylpiperidin-4-yl)methoxy)-3,4-dihydroquinazolin-4-one (12.7 g, 70%).

Workup

  1. temperatureHeating
  2. additionafter the last addition
  3. temperatureAfter cooling
  4. customthe volatiles were removed under vacuum
  5. dissolutionThe solid was dissolved in ethanol (100 ml)
  6. customThe precipitate was removed by filtration
  7. concentrationthe filtrate was concentrated to a final volume of 100 ml
  8. temperatureThe suspension was cooled to 5° C.
  9. filtrationthe solid was collected by filtration
  10. washwashed with cold ethanol
  11. customdried under vacuum overnight at 60° C.

Sources & evidence

ORD record
ord-2d51471139874b3a844b51adb6d211f9
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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