Reaktion #598855

Reaktionsgleichung

K2CO3

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

2-iodopropane

→

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}(propan-2-yl)amino)cyclobutyl]propanoate

Lösungsmittel

MeCN

EtOAc

Reaktionsbedingungen

Aufarbeitung

1. 1
   Filtrationfiltered
2. 2
   Sonstigeevaporated to dryness
3. 3
   SonstigePurification by silica gel chromatography
4. 4
   Wascheneluting with 7N NH3 in MeOH:DCM (1:99-5:95)

Vorschrift

K2CO3 (528.92 mg, 3.83 mmol) was added to a solution of 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 (1.00 g, 1.91 mmol) and 2-iodopropane (0.57 ml, 5.74 mmol) in MeCN and stirred at 95° C. in a sealed tube for 18 hours. The reaction mixture was diluted with EtOAc (20 ml), filtered and evaporated to dryness. Purification by silica gel chromatography, eluting with 7N NH3 in MeOH:DCM (1:99-5:95) gave the desired product as a colourless oil, 700 mg (65%); MS (ESI+) for C30H40N6O5 m/z 565.70 [M+H]+; HPLC purity 96% (ret. time, 1.48 min); 1H NMR (500 MHz, CHLOROFORM-d) δH ppm 8.35 (d, J=3.5 Hz, 1H), 7.88 (d, J=3.2 Hz, 1H), 7.44-7.29 (m, 5H), 6.03 (t, J=2.2 Hz, 1H), 5.62-5.42 (m, 3H), 5.10 (d, J=3.3 Hz, 2H), 5.06-4.92 (m, 1H), 4.26 (dt, J=9.9, 3.4 Hz, 1H), 3.46-2.84 (m, 2H), 2.88-2.61 (m, 1H), 2.51 (ddd, J=14.0, 9.1, 7.5 Hz, 1H), 2.33-2.15 (m, 2H), 2.50-2.13 (m, 2H), 2.16-1.74 (m, 4H), 1.60 (s, 3H), 1.43-1.35 (m, 4H), 0.96 (d, J=6.7 Hz, 3H), 0.79 (d, J=6.6 Hz, 3H).

Quelle