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

HRID 226982Notes

Reaction equation

HRID 226982 reaction equation
C[Si](C)(C)N[Si](C)(C)C.[K].[CH3:11][C:12]1[CH:13]=[C:14]([CH:29]=[CH:30][C:31]=1[CH3:32])[C:15]([C:17]1[C:26](=[O:27])[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([CH3:28])[N:24]=2)[NH:19][CH:18]=1)=[O:16].[Br:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([CH2:40]Br)[N:35]=1.O>O1CCCC1.C(OCC)(=O)C>[Br:33][C:34]1[N:35]=[C:36]([CH2:40][N:19]2[C:20]3[C:25](=[N:24][C:23]([CH3:28])=[CH:22][CH:21]=3)[C:26](=[O:27])[C:17]([C:15](=[O:16])[C:14]3[CH:29]=[CH:30][C:31]([CH3:32])=[C:12]([CH3:11])[CH:13]=3)=[CH:18]2)[CH:37]=[CH:38][CH:39]=1

Participants

7

Reactant 4

HCID 962WaterHCID 129547962-Bromo-6-(bromomethyl)pyridineHCID 45051783Silanamine, 1,1,1-trimethyl-N-(trimethylsilyl)-, potassium saltHCID 577547833-(3,4-Dimethyl-benzoyl)-6-methyl-1H-[1,5]naphthyridin-4-one

Product 1

HCID 577546191-(6-Bromo-pyridin-2-ylmethyl)-3-(3,4-dimethyl-benzoyl)-6-methyl-1H-[1,5]naphthyridin-4-one

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Potassium hexamethyldisilazane (0.49 mL, 0.246 mmol, 0.5 M in THF) was added to a solution of 3-(3,4-Dimethyl-benzoyl)-6-methyl-1H-[1,5]naphthyridin-4-one (60 mg, 0.205) in 2 mL of tetrahydrofuran. After the reaction was stirred at room temperature for 20 minutes 2-bromo-6-bromomethyl-pyridine (61.8 mg, 0.246 mmol) was added and stirred overnight at room temperature. Water and ethyl acetate were added and the two phases were separated. The aqueous phase was extracted with ethyl acetate (3×20 mL). The combined organic layers were dried with magnesium sulfate, filtered and concentrated in vacuo. The crude brown solid was purified by reverse phase HPLC with a C18 column, gradient of 20-70% acetonitrile—0.1% TFA to yield 1-(6-Bromo-pyridin-2-ylmethyl)-3-(3,4-dimethyl-benzoyl)-6-methyl-1H-[1,5]naphthyridin-4-one as an off white solid. LC-MSD, m/z for C24H20BrN3O2 [M+H]: 462.07 LC retention time on HPLC, C18 column gradient 20-95% acetonitrile with 0.1% TFA in 4 minutes: 2.3 min.

Workup

  1. additionwas added
  2. customthe two phases were separated
  3. extractionThe aqueous phase was extracted with ethyl acetate (3×20 mL)
  4. dry with materialThe combined organic layers were dried with magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude brown solid was purified by reverse phase HPLC with a C18 column, gradient of 20-70% acetonitrile—0.1% TFA

Sources & evidence

ORD record
ord-116c912e829d42e58ac37d29d81abc9a
Source dataset
uspto-grants-2009_07
Patent number
US07557213B2

Reaction notes

Loading…