1,8-Diazabicyclo(5.4.0)undec-7-ene → Butanoic acid, 2-((9-(1-methylethyl)-6-((phenylmethyl)amino)-9H-purin-2-yl)amino)-, (2R)-

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Reaktionsbedingungen

Reaktionsschritte

Benzyl-(2-fluoro-9-isopropyl-9H-purin-6-yl)-amine (151 mg, 0.5 mmol) was dissolved in NMP (5 mL) and DBU (1.5 mL, 10 mmol). (R)-(−)-2-Aminobutyric acid (99% ee/GLC; 1.03 g, 10 mmol) was then added and the mixture was stirred under N2 at 160° C. for 1 h. After cooling, the mixture was diluted with citric acid (10% aq solution) and CH2Cl2 (25 mL each). The phases were separated and the organic fraction was extracted with brine (2×10 mL), dried over MgSO4, filtered, and evaporated. The residue was redissolved in MeCN and was fractionated by preparative RP-HPLC (Vydac 218TP1022, 9 mL/min, 22.5-32.5% MeCN in H2O containing 0.1% CF3COOH over 40 min). Appropriate fractions were pooled and lyophilised to afford the pure title compound (137 mg, 74.4%) as an amorphous off-white solid. Anal. RP-HPLC (Vydac 218TP54, 1 mL/min): tR=16.04 min (0-60% MeCN), 15.95 min (22.5-32.5% MeCN in H2O containing 0.1% CF3COOH over 20 min), purity: >98% (λ=214 nm). 1H-NMR (d6-DMSO, 300 MHz) δ: 0.95 (t, J=7.3 Hz, 3H, CH2CH3); 1.51 (d, J=6.7 Hz, 6H, CH(CH3)2); 1.78 (m, J=7.3 Hz, 2H, CH2CH3); 4.27 (m, 1H, CHCH2); 4.64 (hept., J=6.7 Hz, 1H, CH(CH3)2); 4.69 (m, 2H, CH2Ph); 7.25-7.41 (m, 6H, ArH). DE-MALDI-TOF MS (α-cyano-4-hydroxycinnamic acid matrix): [M+H]+=369.41. FAB-MS: [M+H]+=369.2033 (C19H25N6O2 requires 369.2039).

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