Propanoic acid, 2-bromo-2-methyl-, ethyl ester → 6-Bromo-3,3-dimethyl-1,4-dihydro-1,8-naphthyridin-2-one
Reaction equation
Br[C:2]([CH3:9])([CH3:8])[C:3]([O:5]CC)=O.[Br:10][C:11]1[CH:12]=[C:13]([CH2:18]Br)[C:14]([NH2:17])=[N:15][CH:16]=1>C1COCC1.C(OCC)(=O)C.[Zn]>[Br:10][C:11]1[CH:12]=[C:13]2[C:14](=[N:15][CH:16]=1)[NH:17][C:3](=[O:5])[C:2]([CH3:8])([CH3:9])[CH2:18]2Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 3
Procedure
A mixture of activated Zn (1.0 g, 15 mmol) and ethyl 2-bromo-2-methylpropanoate (1.24 mL, 6.4 mmol) in THF (8 mL) were added together at 0° C. and stirred for 6 h while warming to room temperature. To this mixture a dropwise solution of 5-bromo-3-(bromomethyl)pyridin-2-amine in THF (5 mL) was added via canula and the reaction mixture was stirred for a further 19 h at rt. The mixture was diluted with ethyl acetate (25 mL) and washed with saturated aqueous NH4Cl (50 mL) and brine (50 mL), dried over magnesium sulphate, and concentrated in vacuo. The crude yellow solid product was triturated with diethyl ether and filtered to obtain the white solid product. Yield 158 mg (49%); 1H NMR (300 MHz, DMSO-d6) δ 10.61 (s, 1H), 8.23 (s, 1H), 7.87 (s, 1H), 2.81 (s, 2H), 1.04 (s, 6H); ESI MS m/z 255, 257 [C10H11N2OBr+H]+.
Workup
- additionwere added together at 0° C.
- stirringthe reaction mixture was stirred for a further 19 h at rt
- washwashed with saturated aqueous NH4Cl (50 mL) and brine (50 mL)
- dry with materialdried over magnesium sulphate
- concentrationconcentrated in vacuo
- customThe crude yellow solid product was triturated with diethyl ether
- filtrationfiltered
- customto obtain the white solid product
Sources & evidence
- ORD record
- ord-8b6243c69d364e818d7be9bec6fc5521
- Source dataset
- uspto-grants-2013_05
- Patent number
- US08450307B2
Reaction notes
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