Formamidine acetate → 6-Methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazolin-4(3H)-one
Reaction equation
[NH2:1][C:2]1[C:7]([C:8]([O:10]CC)=O)=[CH:6][C:5]([O:13][CH3:14])=[C:4]([O:15][CH2:16][CH:17]2[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]2)[CH:3]=1.C(O)(=O)C.[CH:28](N)=[NH:29]>COCCO>[CH3:14][O:13][C:5]1[CH:6]=[C:7]2[C:2](=[CH:3][C:4]=1[O:15][CH2:16][CH:17]1[CH2:18][CH2:19][N:20]([CH3:23])[CH2:21][CH2:22]1)[N:1]=[CH:28][NH:29][C:8]2=[O:10]Participants
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 over 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-7-(1-methylpiperidin-4-ylmethoxy)-3,4-dihydroquinazolin-4-one (12.7 g, 70%).
Workup
- temperatureHeating
- additionafter the last addition
- temperatureAfter cooling
- customthe volatiles were removed under vacuum
- dissolutionThe solid was dissolved in ethanol (100 ml)
- customThe precipitate was removed by filtration
- concentrationthe filtrate was concentrated to a final volume of 100 ml
- temperatureThe suspension was cooled to 5° C.
- filtrationthe solid was collected by filtration
- washwashed with cold ethanol
- customdried under vacuum overnight at 60° C.
Sources & evidence
- ORD record
- ord-d094b5ec3c4f4511ab7b1280f2482a27
- Source dataset
- uspto-grants-2014_02
- Patent number
- US08642608B2
Reaction notes
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