Reaktion #51532

Reaktionsgleichung

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

Ausbeute 88.1%

Lösungsmittel

acetic acid

2-butanone

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwere added
2. 2
   Temperaturwhile 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
   SonstigeThe organic layer was separated
5. 5
   Extraktionthe aqueous layer was reverse-extracted with 2-butanone (30 ml)
6. 6
   Waschenwhich 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
   FiltrationAfter 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
    Temperaturthe mixture was heated
13. 13
    Temperaturto reflux for 40 minutes
14. 14
    Temperaturto 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
    FiltrationThe crystals were filtered
19. 19
    Waschenwashed with cold acetonitrile/water=5/3(5 ml)
20. 20
    SonstigeThe resulting crystals were dried under vacuum at 50° C.

Vorschrift

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%).

Quelle