1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → HCID 59309802, compound

A mixture of 3,5-dibromo-2-(tert-butoxycarbonylamino)pyrazine (0.26 g), 2-chloro-5-(2,3-difluoro-6-methoxybenzyloxy)-4-methoxyaniline (0.25 g), tris(dibenzylideneacetone)-dipalladium(0) (34 mg), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (43 mg) and sodium tert-butoxide (0.1 g) in tetrahydrofuran (5 mL) was heated at reflux under an argon atmosphere for 1 hour. The reaction mixture was cooled to room temperature. To the reaction mixture was added ethyl acetate, and the insoluble material was removed by filtration. The filtrate was washed with 1 mol/L hydrochloric acid, water and brine successively, and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. To the residue were added methylene chloride (5 mL) and trifluoroacetic acid (1 mL), and the mixture was stirred at room temperature for 3 hours. The reaction mixture was poured into a saturated aqueous sodium hydrogen carbonate solution, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was dissolved in N,N-dimethylformamide (3 mL). To the solution were added 1,1′-carbonyldiimidazole (58 mg) and sodium hydride (55%, 32 mg) under ice-cooling, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into 1 mol/L hydrochloric acid, and the resulting mixture was extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=1/1) to give the title compound (84 mg).

1. temperaturewas heated
2. temperatureat reflux under an argon atmosphere for 1 hour
3. customthe insoluble material was removed by filtration
4. washThe filtrate was washed with 1 mol/L hydrochloric acid, water and brine successively
5. dry with materialdried over anhydrous magnesium sulfate
6. customthe solvent was removed under reduced pressure
7. additionTo the residue were added methylene chloride (5 mL) and trifluoroacetic acid (1 mL)
8. additionThe reaction mixture was poured into a saturated aqueous sodium hydrogen carbonate solution
9. extractionthe resulting mixture was extracted with ethyl acetate
10. washThe extract was washed with water and brine
11. dry with materialdried over anhydrous magnesium sulfate
12. customThe solvent was removed under reduced pressure
13. dissolutionthe residue was dissolved in N,N-dimethylformamide (3 mL)
14. additionTo the solution were added 1,1′-carbonyldiimidazole (58 mg) and sodium hydride (55%, 32 mg) under ice-
15. temperaturecooling
16. stirringthe mixture was stirred at room temperature for 1 hour
17. additionThe reaction mixture was poured into 1 mol/L hydrochloric acid
18. extractionthe resulting mixture was extracted with ethyl acetate
19. washThe extract was washed with brine
20. dry with materialdried over anhydrous magnesium sulfate
21. customThe solvent was removed under reduced pressure
22. customthe residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=1/1)

ORD record

ord-30b8a8149c514aaf93c5288a8381db90

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08217069B2