2-Bromo-6-(bromomethyl)pyridine → 1-(6-Bromo-pyridin-2-ylmethyl)-3-(3-fluoro-4-methoxy-benzoyl)-6-methyl-1H-[1,5]naphthyridin-4-one
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[O:22][CH3:23])[C:5]([C:7]1[C:16](=[O:17])[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([CH3:18])[N:14]=2)[NH:9][CH:8]=1)=[O:6].[Br:24][C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([CH2:31]Br)[N:26]=1>CN(C)C=O>[Br:24][C:25]1[N:26]=[C:27]([CH2:31][N:9]2[C:10]3[C:15](=[N:14][C:13]([CH3:18])=[CH:12][CH:11]=3)[C:16](=[O:17])[C:7]([C:5](=[O:6])[C:4]3[CH:19]=[CH:20][C:21]([O:22][CH3:23])=[C:2]([F:1])[CH:3]=3)=[CH:8]2)[CH:28]=[CH:29][CH:30]=1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
Experimental conditions analogous to those described for Step 3 of Example 1 were used with 110 mg (0.352 mmol) of 3-(3-Fluoro-4-methoxy-benzoyl)-6-methyl-1H-[1,5]naphthyridin-4-one, 106.1 mg (0.423 mmol) of 2-bromo-6-bromomethyl-pyridine, 16.9 mg (0.423 mmol, 60% dispersion in oil), and 2 mL of N,N dimethylformamide. The crude product was purified by flash column chromatography using a gradient of 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 yield 1-(6-Bromo-pyridin-2-ylmethyl)-3-(3-fluoro-4-methoxy-benzoyl)-6-methyl-1H-[1,5]naphthyridin-4-one. LC-MSD, m/z for C23H17BrFN3O3 [M+H]: 482.04 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-861f4a1334e549018b46e506a87b9eda
- Source dataset
- uspto-grants-2009_07
- Patent number
- US07557213B2
Reaction notes
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