Dimethylformamide → 1-(6-Bromo-pyridin-2-ylmethyl)-3-(3-fluoro-4-methoxy-benzoyl)-6-methyl-1H-[1,5]naphthyridin-4-one

HRID 227019Notes

Reaction equation

HRID 227019 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:18]=[CH:19][C:20]=1[O:21][CH3:22])[C:5]([C:7]1[C:16](=[O:17])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][N:14]=2)[NH:9][CH:8]=1)=[O:6].[Br:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([CH2:30]Br)[N:25]=1.[CH3:32]N(C)C=O>>[Br:23][C:24]1[N:25]=[C:26]([CH2:30][N:9]2[C:10]3[C:15](=[N:14][C:13]([CH3:32])=[CH:12][CH:11]=3)[C:16](=[O:17])[C:7]([C:5](=[O:6])[C:4]3[CH:18]=[CH:19][C:20]([O:21][CH3:22])=[C:2]([F:1])[CH:3]=3)=[CH:8]2)[CH:27]=[CH:28][CH:29]=1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 129547962-Bromo-6-(bromomethyl)pyridineHCID 577545673-(3-Fluoro-4-methoxy-benzoyl)-1H-[1,5]naphthyridin-4-one

Product 1

HCID 577546691-(6-Bromo-pyridin-2-ylmethyl)-3-(3-fluoro-4-methoxy-benzoyl)-6-methyl-1H-[1,5]naphthyridin-4-one

Procedure

Experimental conditions analogous to those described for Step 3 of Example 1 were used with 120 mg (0.402 mmol) of 3-(3-Fluoro-4-methoxy-benzoyl)-1H-[1,5]naphthyridin-4-one, 121.1 mg (0.483 mmol) of 2-bromo-6-bromomethyl-pyridine, 19.3 mg (0.483 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 C22H15BrFN3O3 [M+H]: 468.03.

Workup

  1. customThe crude product was purified by flash column chromatography
  2. customfurther purified on the reverse phase HPLC with a C18 column, gradient of 20-70% acetonitrile—0.1% TFA

Sources & evidence

ORD record
ord-5e6baa09830d4721a280dd403edfbab6
Source dataset
uspto-grants-2009_07
Patent number
US07557213B2

Reaction notes

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