Sodium hydride → 1-(4-methoxybenzyl)-7-bromo-1,5-naphthyridin-2(1H)-one

HRID 509631Notes

Reaction equation

HRID 509631 reaction equation
[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8](=[O:12])[NH:9]2)=[N:4][CH:3]=1.[H-].[Na+].Cl[CH2:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=1>CN(C=O)C>[CH3:24][O:23][C:20]1[CH:21]=[CH:22][C:17]([CH2:16][N:9]2[C:10]3[C:5](=[N:4][CH:3]=[C:2]([Br:1])[CH:11]=3)[CH:6]=[CH:7][C:8]2=[O:12])=[CH:18][CH:19]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 699934-Methyloxybenzyl chlorideHCID 57815430HCID 57815430, compound

Product 1

HCID 679930111-(4-methoxybenzyl)-7-bromo-1,5-naphthyridin-2(1H)-oneYield 45.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
35 °C

Procedure

To a stirred solution of 7-bromo-1,5-naphthyridin-2(1H)-one (C-4) (29 g, 128.9 mmol, 1.0 eq) in DMF (200 mL) was added sodium hydride (60% in mineral oil, 7.73 g, 193.3 mmol, 1.5 eq) in portions at RT, the mixture was stirred at 30 to 40° C. for 1 h. 1-(Chloromethyl)-4-methoxybenzene (30.28 g, 193.3 mmol, 1.5 eq) was added dropwise. The resulting mixture was stirred at 30 to 40° C. overnight and quenched with water (500 mL) and extracted with ethyl acetate (5×200 mL). The combined organic layers were washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel (10-50% ethyl acetate/petroether) to afford the desired product, 1-(4-methoxybenzyl)-7-bromo-1,5-naphthyridin-2(1H)-one (C-5) (20.2 g, 45.4% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ: 8.61 (s, 1H), 8.15 (s, 1H), 8.00 (d, J=10 Hz, 1H), 7.18 (d, J=8.4 Hz, 2H), 7.02 (d, J=9.6 Hz, 1H), 6.89 (d, J=8.8 Hz, 2H), 5.45 (s, 2H), 3.71 (s, 3H); ESI-MS m/z: 345.1 [M+H]+.

Workup

  1. stirringThe resulting mixture was stirred at 30 to 40° C. overnight
  2. customquenched with water (500 mL)
  3. extractionextracted with ethyl acetate (5×200 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. customthe residue was purified by flash column chromatography on silica gel (10-50% ethyl acetate/petroether)

Sources & evidence

ORD record
ord-91ad0f27903449df984cc93ec9e9a5a8
Source dataset
uspto-grants-2015_08
Patent number
US09096590B2

Reaction notes

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