Ethylenediamine → Carbazole

Temperature

55 °C

3,6-Bis-(5-indolyl)carbazole-2′,2′-dicarboxylic acid diethyl ester (0.7 mmol) was dissolved in 3.5 mL ethylenediamine in an amber glass vial with a Teflon screw-cap and heated at 55° C. in a sand-bath overnight. The excess amine was removed under vacuum and the residue was dissolved in 7 mL DMSO, 0.7 mL TFA was added and the solution was added up to 35 mL by H2O. The solution was purified by preparative HPLC in 7 injections. Fractions containing 3,6-Bis-(5-indolyl)carbazole-2′,2′-bis(2-aminoethyl)carboxamide were pooled and evaporated. The residues were combined and used in the next step as such. Step 5: 3,6-Bis-(5-indolyl)carbazole-2′,2′-bis(2-aminoeth-1-yl)carboxamide bistrifluoroacetate (0.5 mmol) was mixed with 2.5 mL DMF, 10 mmol diisopropylethyamine and 5 mmol pyrazole-1-carboxamidine hydrochloride were added and the resulting solution was heated at 55° C. for 24 hr. The solvent was removed under vacuum and the residue was dissolved in 5 mL DMSO, 0.5 mL TFA was added and the solution was added up to 25 mL by H2O. The solution was purified by preparative HPLC in 5 injections. Appropriate fractions were pooled and evaporated. The residue was dissolved in 5 mL MeOH, divided into 5 centrifuge tubes and cooled in dry ice for 5 min. One mL of 2 N HCl solution in dioxane was added to each tube and the solutions were immediately diluted to 40 mL each by cold Et2O. The suspensions were centrifuged and the supernatant liquids were decanted. The cakes were dissolved in 1 mL MeOH each and precipitated with cold Et2O. The suspensions were centrifuged and the supernatant liquids were decanted. The residues were dissolved in water and lyophilized to yield 3,6-bis{2-[N-2-guanidinoeth-1-yl)amido]-1H-indol-5-yl}-9H-carbazole.

1. customscrew-cap
2. customThe excess amine was removed under vacuum
3. dissolutionthe residue was dissolved in 7 mL DMSO
4. addition0.7 mL TFA was added
5. additionthe solution was added up to 35 mL by H2O
6. customThe solution was purified by preparative HPLC in 7 injections
7. additionFractions containing 3,6-Bis-(5-indolyl)carbazole-2′,2′-bis(2-aminoethyl)carboxamide
8. customevaporated
9. additionwere added
10. temperaturethe resulting solution was heated at 55° C. for 24 hr
11. customThe solvent was removed under vacuum
12. dissolutionthe residue was dissolved in 5 mL DMSO
13. addition0.5 mL TFA was added
14. additionthe solution was added up to 25 mL by H2O
15. customThe solution was purified by preparative HPLC in 5 injections
16. customevaporated
17. dissolutionThe residue was dissolved in 5 mL MeOH
18. temperaturecooled in dry ice for 5 min
19. additionOne mL of 2 N HCl solution in dioxane was added to each tube
20. additionthe solutions were immediately diluted to 40 mL each by cold Et2O
21. customthe supernatant liquids were decanted
22. dissolutionThe cakes were dissolved in 1 mL MeOH each and
23. customprecipitated with cold Et2O
24. customthe supernatant liquids were decanted
25. dissolutionThe residues were dissolved in water

ORD record

ord-98ee03175e19442bb65985f07dc21b6a

Source dataset

uspto-grants-2005_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06951880B2