Reaktion #168514

Reaktionsgleichung

D-(+)-xylose

hydrochloride

N-{4-[4-(2-aminoethoxy)phenyl]butyl}-N′-(3,5-diamino-6-chloro-pyrazine-2-carbonyl)guanidine

sodium cyanoborohydride

→

compound 23

Ausbeute 20.6%

N-[4-(4-{2-[bis-((2R,3S,4R)-2,3,4,5-tetrahydroxypentyl)amino]ethoxy}-phenyl)butyl]-N′-(3,5-diamino-6-chloropyrazine-2-carbonyl)guanidine dihydrochloride

Ausbeute 20.6%

Lösungsmittel

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThen the solution was cooled to −78° C.
2. 2
   workup.STIRRINGThe reaction mixture was stirred at −78° C. for 2 h and at room temperature for 4 d
3. 3
   SonstigeAfter this time, the solvent was removed under reduced pressure
4. 4
   Waschenthe residue was washed with water
5. 5
   SonstigeThe formed yellow solid was isolated
6. 6
   Sonstigedried under vacuum
7. 7
   workup.DISSOLUTIONThen the residue was re-dissolved in 5% HCl
8. 8
   Sonstigethe solvent was removed at reduced pressure
9. 9
   workup.DISSOLUTIONThe obtained compound was dissolved in water containing 0.1% TFA
10. 10
    Sonstigepurified by preparative HPLC (C 18 Luna column from Phenomenex 250×21.2 mm, 5μ, isocratic method, water/acetonitrile=80%:20%)
11. 11
    workup.ADDITIONThe fractions containing the target compound
12. 12
    Sonstigethe solvent was removed under reduced pressure
13. 13
    workup.DISSOLUTIONThe residue was dissolved in 5% HCl
14. 14
    Sonstigesolvent was removed under reduced pressure (twice)
15. 15
    workup.DISSOLUTIONThe resulting yellow powder was dissolved in water

Vorschrift

D-(+)-xylose (0.35 g, 2.6 mmol) was added to a solution of hydrochloride 4 (0.3 g, 0.65 mmol) in methanol (20 mL) and the mixture was stirred for 20 min at room temperature. Then the solution was cooled to −78° C. and sodium cyanoborohydride (0.17 g, 2.6 mmol) was added. The reaction mixture was stirred at −78° C. for 2 h and at room temperature for 4 d. After this time, the solvent was removed under reduced pressure and the residue was washed with water. The formed yellow solid was isolated and dried under vacuum. Then the residue was re-dissolved in 5% HCl and the solvent was removed at reduced pressure. The obtained compound was dissolved in water containing 0.1% TFA and purified by preparative HPLC (C 18 Luna column from Phenomenex 250×21.2 mm, 5μ, isocratic method, water/acetonitrile=80%:20%). The fractions containing the target compound were combined and the solvent was removed under reduced pressure. The residue was dissolved in 5% HCl and solvent was removed under reduced pressure (twice). The resulting yellow powder was dissolved in water and the solution was lyophylized to give 34 mg (7%) of compound 23 as a yellow solid. 1H NMR (300 MHz, CD3OD) δ 1.64 (br s., 4H), 2.62 (m, 2H), 3.30 (m, 4H), 3.35-3.70 (m, 13H), 4.23 (m, 2H), 4.47 (m, 2H), 6.95 (d, 2H), 7.15 (d, 2H). m/z (APCI)=689 [C28H45ClN8O10+H]+. [α]D25=−16.1° (c=0.5, MeOH).

Quelle