Reaktion #598854

Reaktionsgleichung

9-[(3aR,4R,6R,6aR)-6-(aminomethyl)-2,2-dimethyl-tetrahydro-2H-furo[3,4-d][1,3]dioxol-4-yl]-9H-purin-6-amine

benzyl 3-(3-oxocyclobutyl)propanoate

acetic acid

DCE

→

desired product

Benzyl 3-[3-({[(3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyl-tetrahydro-2H-furo[3,4-d][1,3]dioxol-4-yl]methyl}amino)cyclobutyl]propanoate

Lösungsmittel

DCE iPrOH

iPrOH

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.WAITcontinued for 1 hour
2. 2
   workup.ADDITIONSTAB (1.28 g, 6.03 mmol) was then added
3. 3
   workup.STIRRINGthe reaction mixture was stirred for 18 hours
4. 4
   SonstigeThe reaction mixture was quenched with 1N Na2CO3 (10 ml)
5. 5
   Extraktionthe product was extracted with DCM (2×30 ml)
6. 6
   TrocknenThis was dried over Na2SO4
7. 7
   Filtrationfiltered
8. 8
   Sonstigeevaporated to dryness
9. 9
   SonstigePurification by silica gel column chromatography
10. 10
    Wascheneluting with 7N NH3 in MeOH:DCM (1:99-3:97)

Vorschrift

A suspension of the 9-[(3aR,4R,6R,6aR)-6-(aminomethyl)-2,2-dimethyl-tetrahydro-2H-furo[3,4-d][1,3]dioxol-4-yl]-9H-purin-6-amine (1.45 g, 4.736 mmol), benzyl 3-(3-oxocyclobutyl)propanoate (1.21 g, 5.209 mmol) and acetic acid (246.45 μl, 4.31 mmol) in DCE:iPrOH (4:1, 50 ml) was stirred at RT for 1 h. A further aliquot of DCE (40 ml) and iPrOH (5 ml) was added to the reaction mixture and continued for 1 hour. STAB (1.28 g, 6.03 mmol) was then added and the reaction mixture was stirred for 18 hours. The reaction mixture was quenched with 1N Na2CO3 (10 ml), and the product was extracted with DCM (2×30 ml). This was dried over Na2SO4, filtered and evaporated to dryness. Purification by silica gel column chromatography, eluting with 7N NH3 in MeOH:DCM (1:99-3:97) gave the desired product as a colourless oil, 1.51 g (58%); MS (ESI+) for C27H34N6O5 m/z 523.65 [M+H]+; HPLC purity 97% (ret. time, 1.43 min); 1H NMR (500 MHz, CHLOROFORM-d) δH ppm 8.35 (d, J=5.3 Hz, 1H), 7.87 (d, J=33.8 Hz, 1H), 7.40-7.29 (m, 5H), 6.08-5.94 (m, 1H), 5.59-5.42 (m, 3H), 5.10 (d, J=4.0 Hz, 2H), 5.03-4.96 (m, 1H), 4.33 (dq, J=7.3, 3.9 Hz, 1H), 3.12 (ddd, J=23.0, 14.6, 7.5 Hz, 1H), 2.85-2.77 (m, 1H), 2.74 (dd, J=12.5, 6.6 Hz, 1H), 2.39-2.07 (m, 4H), 1.90-1.64 (m, 5H), 1.61 (s, 4H), 1.38 (s, 3H), 1.28-1.06 (m, 1H).

Quelle