반응 #51532

반응 방정식

2-aminoethanol

Citric acid monohydrate

5-(N-benzyl-N-methylaminomethyl)-1-(2,6-difluorobenzyl)-5-methyl-6-(4-nitrophenyl)-3-phenylthieno[2,3-d]pyrimidine-2,4(1H, 3H)-dione

water

→

6-(4-aminophenyl)-5-(N-benzyl-N-methylaminomethyl)-1-(2,6-difluorobenzyl)-3-phenylthieno[2,3-d]pyrimidine-2,4(1H, 3H)-dione

수율 88.1%

용매

acetic acid

2-butanone

반응 조건

후처리

1. 1
   workup.ADDITIONwere added
2. 2
   온도while the temperature of the solution was maintained below 40° C.
3. 3
   workup.STIRRINGthe mixture was stirred at room temperature for 20 minutes
4. 4
   기타The organic layer was separated
5. 5
   추출the aqueous layer was reverse-extracted with 2-butanone (30 ml)
6. 6
   세척which was washed by addition of an aqueous saturated sodium hydrogen carbonate solution (40 ml) and sodium chloride (7.00 g)
7. 7
   workup.ADDITIONActive carbon (0.3 g) was added to the organic layer
8. 8
   workup.STIRRINGthe mixture was stirred at room temperature for 10 minutes
9. 9
   여과After active carbon was filtered
10. 10
    workup.DISTILLATIONthe organic solvent was distilled off under reduced pressure, acetonitrile (15 ml)
11. 11
    workup.ADDITIONwas added
12. 12
    온도the mixture was heated
13. 13
    온도to reflux for 40 minutes
14. 14
    온도to cool to room temperature for 1 hour
15. 15
    workup.ADDITIONwater (9 ml) was slowly added dropwise
16. 16
    workup.STIRRINGThe mixture was stirred at room temperature for 30 minutes
17. 17
    workup.STIRRINGstirred at 0° C. for 30 minutes
18. 18
    여과The crystals were filtered
19. 19
    세척washed with cold acetonitrile/water=5/3(5 ml)
20. 20
    기타The resulting crystals were dried under vacuum at 50° C.

실험 절차

5-(N-benzyl-N-methylaminomethyl)-1-(2,6-difluorobenzyl)-5-methyl-6-(4-nitrophenyl)-3-phenylthieno[2,3-d]pyrimidine-2,4(1H, 3H)-dione (3.00 g, 4.80 mmol) was dissolved in acetic acid (6.00 ml). A 20% titanium (III) chloride solution (22.22 g, 28.82 mmol) was added thereto, and the mixture was stirred at room temperature for 1 hour (slight exothermic). Citric acid monohydrate (7.07 g) was added to the reaction solution to dissolve it, and water (30 ml) and 2-butanone (50 ml) were added thereto. 2-aminoethanol (15 ml) was added thereto while the temperature of the solution was maintained below 40° C., and the mixture was stirred at room temperature for 20 minutes. The organic layer was separated, and the aqueous layer was reverse-extracted with 2-butanone (30 ml). The organic layers were combined, which was washed by addition of an aqueous saturated sodium hydrogen carbonate solution (40 ml) and sodium chloride (7.00 g). Active carbon (0.3 g) was added to the organic layer, and the mixture was stirred at room temperature for 10 minutes. After active carbon was filtered, the organic solvent was distilled off under reduced pressure, acetonitrile (15 ml) was added thereto, and the mixture was heated to reflux for 40 minutes. The mixture was allowed to cool to room temperature for 1 hour, and water (9 ml) was slowly added dropwise. The mixture was stirred at room temperature for 30 minutes, and stirred at 0° C. for 30 minutes. The crystals were filtered and washed with cold acetonitrile/water=5/3(5 ml). The resulting crystals were dried under vacuum at 50° C. to give 6-(4-aminophenyl)-5-(N-benzyl-N-methylaminomethyl)-1-(2,6-difluorobenzyl)-3-phenylthieno[2,3-d]pyrimidine-2,4(1H, 3H)-dione (2.51 g, 4.23 mmol, 88.1%).

출처