Bicarbonate Ion → TFA-ap-dC

HRID 500306Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 500306
I[C:2]1[C:3]([NH2:17])=[N:4][C:5](=[O:16])[N:6]([CH:15]=1)[C@@H:7]1[O:14][C@H:11]([CH2:12][OH:13])[C@@H:9]([OH:10])[CH2:8]1.C(N(CC)CC)C.[F:25][C:26]([F:34])([F:33])[C:27]([NH:29][CH2:30][C:31]#[CH:32])=[O:28].N(CO[C@@H]1[C@@H](CO)O[C@@H](N2C=C(C#CCNC(=O)C(F)(F)F)C(=O)NC2=O)C1)=[N+]=[N-].C(=O)(O)[O-]>CN(C=O)C.[Cu]I>[F:25][C:26]([F:34])([F:33])[C:27]([NH:29][CH2:30][C:31]#[C:32][C:2]1[C:3]([NH2:17])=[N:4][C:5](=[O:16])[N:6]([CH:15]=1)[C@@H:7]1[O:14][C@H:11]([CH2:12][OH:13])[C@@H:9]([OH:10])[CH2:8]1)=[O:28]

Komponenten

8

Edukt 5

HCID 769Bicarbonate IonHCID 8471TriethylamineHCID 65050IbacitabineHCID 110948052,2,2-trifluoro-N-(prop-2-yn-1-yl)acetamideHCID 866136103'-O-Azidomethyl-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2'-deoxyuridine

Produkt 1

HCID 14768553TFA-ap-dC

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of 5-iodo-2′-deoxycytidine (10 g, 28.32 mmol) in DMF (200 ml) in a light protected round bottom flask under Argon atmosphere, was added CuI (1.08 g, 5.67 mmol), triethylamine (7.80 ml, 55.60 mmol), 2,2,2-trifluoro-N-prop-2-ynyl-acetamide (12.8 g, 84.76 mmol) and at last Pd(PPh)3)4 (3.27 g, 2.83 mmol). After 18 hours at room temperature, dowex bicarbonate (20 mg) was added and the mixture was stirred for a further 1 h. Filtration and evaporation of the volatiles under reduced pressure gave a residue that was purified by flash chromatography on silica gel (CH2Cl2, CH2Cl2:EtOAc 1:1, EtOAc:MeOH 9:1). The expected product (7) was obtained as a beige solid in quantitative yield. 1H NMR (D2O) δ 2.24-2.17 (m, 1H, H-2′), 2.41-2.37 (m, 1H, H-2′), 3.68 (dd, J=12.5, 5.0 Hz, 1H, H-5′), 3.77 (dd, J=12.5, 3.2 Hz, 1H, H-5′), 3.99 (m, 1H, H-4′), 4.27 (s, 2H, CH2N), 4.34 (m, 1H, H-3′), 6.11 (t, J=6.3 Hz, 1H, H-1′), 8.1 (br s, 1H, NH); MS (ES): m/z (%) (M−H) 375 (100).

Aufarbeitung

  1. filtrationFiltration and evaporation of the volatiles under reduced pressure
  2. customgave a residue that
  3. customwas purified by flash chromatography on silica gel (CH2Cl2, CH2Cl2:EtOAc 1:1, EtOAc:MeOH 9:1)

Quellen und Nachweise

ORD-Eintrag
ord-fa8eae02176b43f4a37a1176455d1e05
Quelldatensatz
uspto-grants-2010_08
Patentnummer
US07771973B2

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