2-(Bromomethyl)-6-methylpyridine → 3-(4-Methoxy-3-methyl-benzoyl)-1-(6-methyl-pyridin-2-ylmethyl)-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[CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([CH3:31])[N:26]=1.C[Si](C)(C)N[Si](C)(C)C.[K]>C1COCC1>[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)[N:11]([CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([CH3:31])[N:26]=3)[CH:10]=2)=[O:8])=[CH:5][C:4]=1[CH3:22]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
Experimental conditions analogous to those described for Step 3 of Example 1 using 75 mg (0.255 mmol) of 3-(4-Methoxy-3-methyl-benzoyl)-1H-[1,5]naphthyridin-4-one, 56.9 mg (0.306 mmol) of 2-bromomethyl-6-methyl-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 38.6 mg of 3-(4-Methoxy-3-methyl-benzoyl)-1-(6-methyl-pyridin-2-ylmethyl)-1H-[1,5]naphthyridin-4-one. LC-MSD, m/z for C24H21N3O3 [M+H]: 400.16 LC retention time on HPLC, C18 column gradient 20-95% acetonitrile with 0.1% TFA in 4 minutes: 1.8 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-58349d37735941e991a4a40e7181726c
- Source dataset
- uspto-grants-2009_07
- Patent number
- US07557213B2
Reaction notes
Loading…