Formamidine acetate → 6-Methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazolin-4(3H)-one

HRID 2233256Notes

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 a period of 4 hours and the reaction was heated for 30 minutes after the last addition. The reaction was cooled, the volatiles were removed in vacuo, and the residue was dissolved in ethanol (100 ml) and dichloromethane (50 ml). The reaction was filtered and the filtrate was concentrated to a final volume of 100 ml. Collection of the precipitated solid by suction filtration (at 5° C.) followed by drying in vacuo yielded 6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)-3,4-dihydroquinazolin-4-one (12.7 g, 70% yield) as a white solid:

Workup

temperaturethe reaction was heated for 30 minutes
additionafter the last addition
temperatureThe reaction was cooled
customthe volatiles were removed in vacuo
dissolutionthe residue was dissolved in ethanol (100 ml)
filtrationThe reaction was filtered
concentrationthe filtrate was concentrated to a final volume of 100 ml
customCollection of the precipitated solid
filtrationby suction filtration (at 5° C.)
customby drying in vacuo

Sources & evidence

ORD record: ord-87f16b85c8eb4f0890bd760306a42aeb
Source dataset: uspto-grants-2010_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07709479B1

Reaction notes

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