Reaktion #598858

Reaktionsgleichung

Sodium triacetoxyborohydride

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

→

product

Ausbeute 61.6%

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

Ausbeute 61.6%

Lösungsmittel

DCE iPrOH

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.WAITthe mixture left
2. 2
   workup.STIRRINGto stir for 18 h at r.t
3. 3
   SonstigeThe reaction mixture was quenched with 1M Na2CO3 solution (10 ml)
4. 4
   Extraktionthe product was extracted with DCM (3×30 ml)
5. 5
   TrocknenThe combined organic layers were dried over Na2SO4
6. 6
   Filtrationfiltered
7. 7
   Sonstigeevaporated to dryness
8. 8
   SonstigePurification by silica gel flash column chromatography
9. 9
   Wascheneluting with 1% 7M NH3 in MeOH

Vorschrift

A suspension of 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 (5.00 g, 16.3 mmol), benzyl 3-(3-oxocyclobutyl)-propanoate (4.17 g, 18.0 mmol) and acetic acid (0.85 ml, 14.8 mmol) in DCE:iPrOH (7:2) (90 ml) was stirred at r.t. for 2 h. Sodium triacetoxyborohydride (4.40 g, 20.8 mmol) was added in portions and the mixture left to stir for 18 h at r.t. The reaction mixture was quenched with 1M Na2CO3 solution (10 ml) and the product was extracted with DCM (3×30 ml). The combined organic layers were dried over Na2SO4, filtered and evaporated to dryness. Purification by silica gel flash column chromatography eluting with 1% 7M NH3 in MeOH:99% DCM gave the product as a yellow oil (5.25 g, 55%, 89% pure): MS (ESI+) for C27H34N6O5 m/z 523.6 [M+H]+; LC purity 89% (ret. time, 1.60 min); 1H NMR (500 MHz, CDCl3) δH 8.35 (d, J=6.0 Hz, 1H), 7.91 (s, 1H), 7.30-7.39 (m, 5H), 6.01 (dd, J=3.0 Hz, 1.6, 1H), 5.72 (br. s., 2H), 5.50 (dt, J=6.4 Hz, 3.3, 1H), 5.10 (d, J=3.8 Hz, 2H), 4.98-5.04 (m, 1H), 4.31-4.38 (m, 1H), 2.97-3.34 (m, 1H), 2.72-2.85 (m, 2H), 2.22-2.35 (m, 3H), 2.14 (td, J=8.3, 4.3 Hz, 1H), 1.73-1.90 (m, 4H), 1.64-1.71 (m, 1H), 1.62 (d, J=1.4 Hz, 3H), 1.39 (s, 3H), 1.10-1.27 (m, 1H).

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