Chloroform → 7-(4-methoxybenzyl)-4-chloro-3-(chloromethyl)-1,7-naphthyridin-8(7H)-one

HRID 1668978Notes

Reaction equation

HRID 1668978 reaction equation
[CH3:1][O:2][C:3]1[CH:23]=[CH:22][C:6]([CH2:7][N:8]2[C:17](=[O:18])[C:16]3[N:15]=[CH:14][C:13](CO)=[C:12](O)[C:11]=3[CH:10]=[CH:9]2)=[CH:5][CH:4]=1.P(Cl)(Cl)([Cl:26])=O.[CH:29]([Cl:32])(Cl)Cl>>[CH3:1][O:2][C:3]1[CH:23]=[CH:22][C:6]([CH2:7][N:8]2[C:17](=[O:18])[C:16]3[N:15]=[CH:14][C:13]([CH2:12][Cl:26])=[C:29]([Cl:32])[C:11]=3[CH:10]=[CH:9]2)=[CH:5][CH:4]=1

Participants

4

Reactant 3

HCID 6212ChloroformHCID 24813Phosphorus oxychlorideHCID 1784907707-(4-methoxybenzyl)-4-hydroxy-3-(hydroxymethyl)-1,7-naphthyridin-8(7H)-one

Product 1

HCID 584664817-(4-methoxybenzyl)-4-chloro-3-(chloromethyl)-1,7-naphthyridin-8(7H)-one

Conditions

Temperature
85 °C

Procedure

7-(4-methoxybenzyl)-4-hydroxy-3-(hydroxymethyl)-1,7-naphthyridin-8(7H)-one (1.1 g, 3.5 mmol) was suspended in chloroform and treated with phosphorous oxychloride (4.9 ml, 53 mmol) and the mixture was stirred at 85° C. After 3 hours, the reaction was cooled down to room temperature and the volatiles were removed under vacuum. Residual phosphorous oxychloride was azeotroped with toluene. The residue was dissolved in chloroform and washed with cold water (2×). The organic layer then washed (2×) with an aqueous saturated solution of sodium bicarbonate, then with water and then brine. The organic layer was then dried with sodium sulfate and purified by column chromatography on silica gel using a gradient of 0 to 5% methanol in DCM to give 7-(4-methoxybenzyl)-4-chloro-3-(chloromethyl)-1,7-naphthyridin-8(7H)-one as a yellow film. MS (M+H)+ 350.

Workup

  1. temperaturethe reaction was cooled down to room temperature
  2. customthe volatiles were removed under vacuum
  3. customResidual phosphorous oxychloride was azeotroped with toluene
  4. dissolutionThe residue was dissolved in chloroform
  5. washwashed with cold water (2×)
  6. washThe organic layer then washed (2×) with an aqueous saturated solution of sodium bicarbonate
  7. dry with materialThe organic layer was then dried with sodium sulfate
  8. custompurified by column chromatography on silica gel using a gradient of 0 to 5% methanol in DCM

Sources & evidence

ORD record
ord-24c881df5bbb468e9950b178a7474f49
Source dataset
uspto-grants-2011_08
Patent number
US07989461B2

Reaction notes

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