2,6-Lutidine → HCID 178438526、化合物

温度

0 °C

A mixture of 4′-({5-oxo-7-propyl-4-[(3a′R,6a′S)-tetrahydrospiro[cyclohexane-1,2′-furo[3,4-d][1,3]dioxol]-4-yl]-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl}methyl)biphenyl-2-carbonitrile (0.14 g), tert-butyl(dimethyl)silyl trifluoromethanesulfonate (0.087 mL), 2,6-lutidine (0.044 mL) and tetrahydrofuran (5 mL) was stirred at 0° C. for 3 hr. The reaction mixture was diluted with ethyl acetate, washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue obtained by silica gel column chromatography was dissolved in dimethyl sulfoxide (5 mL), and the mixture was added to a mixture of hydroxylammonium chloride (0.26 g), sodium hydrogen carbonate (0.42 g) and dimethyl sulfoxide (5 mL), which had been stirred in advance at 40° C. for 30 min. The reaction mixture was stirred at 90° C. for 16 hr, diluted with ethyl acetate, washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was dissolved in tetrahydrofuran (10 mL). N,N′-Carbonyldiimidazole (0.049 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.041 mL) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous potassium hydrogensulfate solution and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was dissolved in tetrahydrofuran (10 mL). Tetrabutylammonium bromide (1.0 M tetrahydrofuran solution, 1.7 mL) was added, and the mixture was stirred at room temperature for 3 hr. The reaction mixture was extracted with 1 N hydrochloric acid and ethyl acetate, and the ethyl acetate layer was washed with saturated brine and concentrated. The residue was purified by silica gel column chromatography to give the title compound as a colorless amorphous solid (0.04 g, 26%).

1. washwashed with water
2. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
3. customThe solvent was evaporated under reduced pressure
4. customThe residue obtained by silica gel column chromatography
5. stirringhad been stirred in advance at 40° C. for 30 min
6. stirringThe reaction mixture was stirred at 90° C. for 16 hr
7. washwashed with water
8. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
9. customThe solvent was evaporated under reduced pressure
10. dissolutionthe residue was dissolved in tetrahydrofuran (10 mL)
11. additionN,N′-Carbonyldiimidazole (0.049 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.041 mL) were added
12. stirringthe mixture was stirred at room temperature for 2 hr
13. additionThe reaction mixture was diluted with ethyl acetate
14. washwashed with saturated aqueous potassium hydrogensulfate solution
15. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
16. customThe solvent was evaporated under reduced pressure
17. dissolutionthe residue was dissolved in tetrahydrofuran (10 mL)
18. additionTetrabutylammonium bromide (1.0 M tetrahydrofuran solution, 1.7 mL) was added
19. stirringthe mixture was stirred at room temperature for 3 hr
20. extractionThe reaction mixture was extracted with 1 N hydrochloric acid and ethyl acetate
21. washthe ethyl acetate layer was washed with saturated brine
22. concentrationconcentrated
23. customThe residue was purified by silica gel column chromatography

ORDレコード

ord-e248e7211e994bf59f43c61b9a7f732a

出典データセット

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08921379B2