Potassium Carbonate → 1-(1-Naphthyl)-2-{2-[(pyrimidin-2-yl)amino]ethoxy}ethanol maleate

Temperature

50 °C

7 ml of water and 7 ml of dioxane were added to 0.7 g of 2-(2-aminoethoxy)-1-(1-naphthyl)ethanol to obtain a solution. To the solution was added 0.32 g of potassium carbonate. The resulting mixture was heated to 50° C. Thereto was added 0.35 g of 2-chloropyrimidine. The resulting mixture was refluxed for 3 hours. Thereto were added 0.32 g of potassium carbonate and 0.35 g of 2-chloropyrimidine. The resulting mixture was further refluxed for 2.5 hours. The reaction mixture was cooled and added to a mixture of 20 mi of ethyl acetate and 20 ml of ice water. The organic layer was separated. The aqueous layer was extracted with 10 ml of ethyl acetate. The extract was combined with the previously separated organic layer. To the combined organic layer was added 15 ml of water and the resulting mixture was adjusted to pH 1.5 with 6N hydrochloric acid. The aqueous layer was separated. The organic layer was extracted with 10 ml of water. The extract was combined with the previously separated aqueous layer. To the combined aqueous layer was added 50 ml of methylene chloride and the resulting mixture was adjusted to pH 10.5 with potassium carbonate. The organic layer was separated, washed with water, and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure. The residue thus obtained was purified by column chromatography (eluant: chloroform/ethanol=20/1) to obtain an oily product. To the oily product were added 4 ml of ethanol and 0.21 g of maleic acid. The resulting mixture was stirred at room temperature for 1 hour. To the reaction mixture was added 2 ml of diethyl ether. The resulting mixture was stirred at the same temperature for 1 hour. The resulting crystals were collected by filtration and dried to obtain 0.53 g of 1-(1-naphthyl)-2-{2-[(pyrimidin-2-yl)amino]ethoxy}-ethanol maleate (compound No. 268).

1. customto obtain a solution
2. temperatureThe resulting mixture was refluxed for 3 hours
3. temperatureThe resulting mixture was further refluxed for 2.5 hours
4. temperatureThe reaction mixture was cooled
5. customThe organic layer was separated
6. extractionThe aqueous layer was extracted with 10 ml of ethyl acetate
7. additionTo the combined organic layer was added 15 ml of water
8. customThe aqueous layer was separated
9. extractionThe organic layer was extracted with 10 ml of water
10. additionTo the combined aqueous layer was added 50 ml of methylene chloride
11. customThe organic layer was separated
12. washwashed with water
13. dry with materialdried over anhydrous magnesium sulfate
14. customThe solvent was removed by distillation under reduced pressure
15. customThe residue thus obtained
16. customwas purified by column chromatography (eluant: chloroform/ethanol=20/1)
17. customto obtain an oily product
18. stirringThe resulting mixture was stirred at the same temperature for 1 hour
19. filtrationThe resulting crystals were collected by filtration
20. customdried

ORD record

ord-78ed53c78b4b4bb99790c5eca541f9b5

Source dataset

uspto-grants-1998_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05719150