反应详情

温度

70 °C

Add 2.6 ml of an 11.25N sodium hydroxide solution at 70° C. to a solution of 1.72 g (14.85 mmol) of cyclobutane-1,1-diyldimethanol [F. X. Tavares, J. Med. Chem. 2004, 47 (21), 5057-5068] in 20 ml of toluene, 8 ml of 1,2-dimethoxyethane and 8 ml of water. After adding 0.10 g (0.30 mmol) of tetra-n-butylammonium hydrogen sulphate and 1.00 g (2.97 mmol) of 4-chloro-5-(4-methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidine, stir the reaction mixture at 70° C. for 17 h. After cooling to room temperature, adjust to pH 7 with concentrated hydrochloric acid. Extract three times with 50 ml of dichloromethane each time. Wash the combined organic extracts with satd. sodium chloride solution, dry over sodium sulphate and filter. Concentrate the filtrate under reduced pressure. Stir the residue in acetonitrile, filter and purify the filtrate by means of preparative RP-HPLC (gradient: water/acetonitrile). 0.30 g (24% of theory) of the desired product are obtained.

1. temperatureAfter cooling to room temperature
2. extractionExtract three times with 50 ml of dichloromethane each time
3. washWash the combined organic extracts with satd
4. dry with materialsodium chloride solution, dry over sodium sulphate
5. filtrationfilter
6. concentrationConcentrate the filtrate under reduced pressure
7. stirringStir the residue in acetonitrile
8. filtrationfilter
9. custompurify the filtrate by means of preparative RP-HPLC (gradient: water/acetonitrile)