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

HRID 729559

Reaktionsgleichung

Reaktionsgleichung von HRID 729559
[CH2:1]([NH:8][C:9]1[N:17]=[C:16](F)[N:15]=[C:14]2[C:10]=1[N:11]=[CH:12][N:13]2[CH:19]([CH3:21])[CH3:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1CCN2C(=NCCC2)CC1.[NH2:33][C@H:34]([CH2:38][CH3:39])[C:35]([OH:37])=[O:36]>CN1C(=O)CCC1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.C(Cl)Cl>[CH2:1]([NH:8][C:9]1[N:17]=[C:16]([NH:33][C@H:34]([CH2:38][CH3:39])[C:35]([OH:37])=[O:36])[N:15]=[C:14]2[C:10]=1[N:11]=[CH:12][N:13]2[CH:19]([CH3:21])[CH3:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Komponenten

7

Edukt 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 439691D-Alpha-aminobutyric acidHCID 17954009Benzyl-(2-fluoro-9-isopropyl-9H-purin-6-yl)-amine

Produkt 1

HCID 3013831Butanoic acid, 2-((9-(1-methylethyl)-6-((phenylmethyl)amino)-9H-purin-2-yl)amino)-, (2R)-Ausbeute 74,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 311Citric AcidLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Reaktionsbedingungen

Temperatur
160 °C

Versuchsvorschrift

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).

Aufarbeitung

  1. temperatureAfter cooling
  2. customThe phases were separated
  3. extractionthe organic fraction was extracted with brine (2×10 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. dissolutionThe residue was redissolved in MeCN
  8. customwas fractionated by preparative RP-HPLC (Vydac 218TP1022, 9 mL/min, 22.5-32.5% MeCN in H2O containing 0.1% CF3COOH over 40 min)

Quellen und Nachweise

ORD-Eintrag
ord-53afadd327784f94b8f4e4362eb3dfbb
Quelldatensatz
uspto-grants-2009_09
Patentnummer
US07582642B2

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