2-Bromo-6-(bromomethyl)pyridine → 1-(6-Bromo-pyridin-2-ylmethyl)-3-(4-methoxy-3-methyl-benzoyl)-1H-[1,5]naphthyridin-4-one
Reaction equation
[CH3:1][O:2][C:3]1[CH:21]=[CH:20][C:6]([C:7]([C:9]2[C:18](=[O:19])[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][N:16]=3)[NH:11][CH:10]=2)=[O:8])=[CH:5][C:4]=1[CH3:22].[Br:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([CH2:30]Br)[N:25]=1.C[Si](C)(C)N[Si](C)(C)C.[K]>C1COCC1>[Br:23][C:24]1[N:25]=[C:26]([CH2:30][N:11]2[C:12]3[C:17](=[N:16][CH:15]=[CH:14][CH:13]=3)[C:18](=[O:19])[C:9]([C:7](=[O:8])[C:6]3[CH:20]=[CH:21][C:3]([O:2][CH3:1])=[C:4]([CH3:22])[CH:5]=3)=[CH:10]2)[CH:27]=[CH:28][CH:29]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
Experimental conditions analogous to those described for Step 1 of Example 2 using 75 mg (0.255 mmol) of 3-(4-Methoxy-3-methyl-benzoyl)-1H-[1,5]naphthyridin-4-one, 76.8 mg (0.306 mmol) of 2-bromo-6-bromomethyl-pyridine, 0.61 mL (0.306 mmol, 0.5 M in toluene) of potassium hexamethyldisilazane, and 2.5 mL of THF. 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 20 mg of 1-(6-Bromo-pyridin-2-ylmethyl)-3-(4-methoxy-3-methyl-benzoyl)-1H-[1,5]naphthyridin-4-one. LC-MSD, m/z for C23H18BrN3O3 [M+H]: 464.05 LC retention time on HPLC, C18 column gradient 20-95% acetonitrile with 0.1% TFA in 4 minutes: 2.0 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-3461c2048d9e41c7ac5852a3eaedfe18
- Source dataset
- uspto-grants-2009_07
- Patent number
- US07557213B2
Reaction notes
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