3,4-Dimethoxy-6-nitrobenzamide → 2-Amino-4,5-dimethoxybenzamide

HRID 277758

Reaction equation

HRID 277758 reaction equation
[CH3:1][O:2][C:3]1[C:11]([O:12][CH3:13])=[CH:10][C:6]([C:7]([NH2:9])=[O:8])=[C:5]([N+:14]([O-])=O)[CH:4]=1.[BH4-].[Na+]>S([O-])([O-])(=O)=O.[Cu+2]>[CH3:1][O:2][C:3]1[C:11]([O:12][CH3:13])=[CH:10][C:6]([C:7]([NH2:9])=[O:8])=[C:5]([NH2:14])[CH:4]=1

Participants

4

Reactant 2

HCID 27361933,4-Dimethoxy-6-nitrobenzamideHCID 4311764Sodium borohydride

Product 1

HCID 108672362-Amino-4,5-dimethoxybenzamide

Reagents, catalysts & solvents 1

HCID 24462Copper SulfateCatalyst

Procedure

The key starting material, 4-chloro-6,7-dimethoxyquinazoline, was prepared according to published procedures (Nomoto, et al., 1990, Chem. Pharm. Bull., 38:1591-1595; Thomas, C. L., 1970, IN:Catalytic Processes and Proven Catalysts, Academic Press, New York, N.Y.) as outlined below in Scheme 1. Specifically, 4,5dimethoxy-2-nitrobenzoic acid (compound 1) was treated with thionyl chloride to form acid chloride, followed by reacting with ammonia to yield 4,5-dimethoxy-2-nitrobenzamide (compound 2). Compound 2 was reduced with sodium borohydride in the presence of catalytic amounts of copper sulphate to give 4,5-dimethoxy-2-aminobenzamide (compound 3), which was directly refluxed with formic acid to yield 6,7-dimethoxyquinazoline-4(3H)-one (compound 4). Compound 4 was refluxed with phosphorus oxytrichloride to give 4-chloro-6,7-dimethoxyquinazoline (compound 5) in good yield.

Sources & evidence

ORD record
ord-b4720f11771d464db43f730bee8a7792
Source dataset
uspto-grants-2002_03
Patent number
US06358962B2

Linked notes

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