1-(6-Bromo-pyridin-2-ylmethyl)-7-methyl-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid methoxy-methyl-amide → 1-(6-Bromo-pyridin-2-ylmethyl)-3-(4-methoxy-3-methyl-benzoyl)-7-methyl-1H-[1,8]naphthyridin-4-one
Reaction equation
CON(C)[C:4]([C:6]1[C:15](=[O:16])[C:14]2[C:9](=[N:10][C:11]([CH3:17])=[CH:12][CH:13]=2)[N:8]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([Br:25])[N:20]=2)[CH:7]=1)=[O:5].[CH3:27][O:28][C:29]1[CH:34]=[CH:33][C:32]([Mg]Br)=[CH:31][C:30]=1[CH3:37]>C1COCC1>[Br:25][C:21]1[N:20]=[C:19]([CH2:18][N:8]2[C:9]3[C:14](=[CH:13][CH:12]=[C:11]([CH3:17])[N:10]=3)[C:15](=[O:16])[C:6]([C:4](=[O:5])[C:32]3[CH:33]=[CH:34][C:29]([O:28][CH3:27])=[C:30]([CH3:37])[CH:31]=3)=[CH:7]2)[CH:24]=[CH:23][CH:22]=1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
Experimental conditions analogous to those described for Step 6 of Example 60 were used with 85 mg (0.204 mmol) of 1-(6-Bromo-pyridin-2-ylmethyl)-7-methyl-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid methoxy-methyl-amide and 0.896 mL 0.448 mL, 0.5 M in THF) of 4-methoxy-3-methylphenylmagnesium bromide in 1 mL of THF. The crude product was purified by flash column chromatography using 20-100% ethyl acetate in hexane and further purified on the reverse phase HPLC with a C18 column, gradient of 20-70% acetonitrile—0.1% TFA to afford 27.9 mg of 1-(6-Bromo-pyridin-2-ylmethyl)-3-(4-methoxy-3-methyl-benzoyl)-7-methyl-1H-[1,8]naphthyridin-4-one as a white solid. LC-MSD, m/z for C24H20BrN3O3 [M+H]: 478.07 LC retention time on HPLC, C18 column gradient 20-95% acetonitrile with 0.1% TFA in 4 minutes: 2.6 min.
Workup
- customThe crude product was purified by flash column chromatography
- customfurther purified on the reverse phase HPLC with a C18 column, gradient of 20-70% acetonitrile—0.1% TFA
Sources & evidence
- ORD record
- ord-3c6fb0a6268a43c6a80bbe38d9aab38f
- Source dataset
- uspto-grants-2009_07
- Patent number
- US07557213B2
Reaction notes
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