9-[(2R)-2-Deoxy-2-C-ethynyl-2-fluoro-beta-D-erythro-furanosyl]-N2-isobutyryl-guanine → 9-[(2R)-2-Deoxy-2-C-ethynyl-2-fluoro-beta-D-erythro-furanosyl]-guanine

HRID 2361723

Reaktionsgleichung

Reaktionsgleichung von HRID 2361723
[C:1]([C@@:3]1([F:25])[C@H:7]([OH:8])[CH2:6][O:5][C@H:4]1[N:9]1[CH:17]=[N:16][C:15]2[C:14](=[O:18])[NH:13][C:12]([NH:19]C(=O)C(C)C)=[N:11][C:10]1=2)#[CH:2]>N.C(OCC)(=O)C>[C:1]([C@@:3]1([F:25])[C@H:7]([OH:8])[CH2:6][O:5][C@H:4]1[N:9]1[CH:17]=[N:16][C:15]2[C:14](=[O:18])[NH:13][C:12]([NH2:19])=[N:11][C:10]1=2)#[CH:2]

Komponenten

4

Edukt 1

HCID 1363472339-[(2R)-2-Deoxy-2-C-ethynyl-2-fluoro-beta-D-erythro-furanosyl]-N2-isobutyryl-guanine

Produkt 1

HCID 1363439289-[(2R)-2-Deoxy-2-C-ethynyl-2-fluoro-beta-D-erythro-furanosyl]-guanine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 222AmmoniaLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

Compound B4 (0.78 g, 1.33 mmol) was dissolved in saturated methanolic ammonia (62 mL) and stirred at room temperature for 20 h. The reaction mixture was then evaporated to dryness under reduced pressure. The residue was dissolved in water and washed twice with ethyl acetate. The aqueous layer was evaporated and purified on reverse phase column chromatography (C 18) eluting with a gradient 2-15% of acetonitrile in water. The residue obtained was then dissolved in hot ethyl acetate, filtered and dried to give D961 (Compound B5) (134 mg, 33%) as a yellow solid. NMR 1H (400 MHz, DMSO-d6): δ 10.70 (ls, 1H, NH), 7.98 (s, 1H, H-8), 6.60 (ls, 2H, NH2), 6.21 (d, 1H, OH-3′, JOH-3′=7.6 Hz), 5.83 (d, 1H, H-1′, J1′-F=16.9 Hz), 5.29 (t, 1H, OH-5′, JOH-5′=5.2 Hz), 4.50 (td, 1H, H-3′, J3′-F=22.8 Hz, J3′-4=9.2 Hz), 3.93-3.81 (m, 3H, H-4′, H-5′ and ethynyl), 3.70 (m, 1H, H-5″). NMR 13C (100 MHz DMSO-d6): δ 157.2 (C-6), 154.3 (C-2), 151.05 (C-4), 135.1 (C-8), 116.7 (C-5), 96.4 (d, C-2′, 1JC-F=182.1 Hz), 87.4 (d, C-1′, 2JC-F=39.2 Hz), 83.1 (d, CCH, JC-F=9.1 Hz), 82.4 (C-4′), 76.2 (d, CCH, 2JC-F=31.2 Hz), 73.2 (d, C-3′, 2JC-F=20.1 Hz), 59.5 (C-5′). NMR 19F (235 MHz, DMSO-d6): δ −158.5 (m). LC/MS (A): (M+H+) 310.1 (5.55 min). LRFAB-MS (GT): 619 (2M+H)+, 310 (M+H)+, 152 (B+H)+, 617 (2M−H)+, 308 (M−H)−. UV: λmax=254 nm.

Aufarbeitung

  1. customThe reaction mixture was then evaporated to dryness under reduced pressure
  2. dissolutionThe residue was dissolved in water
  3. washwashed twice with ethyl acetate
  4. customThe aqueous layer was evaporated
  5. custompurified on reverse phase column chromatography (C 18)
  6. washeluting with a gradient 2-15% of acetonitrile in water
  7. customThe residue obtained
  8. filtrationfiltered
  9. customdried

Quellen und Nachweise

ORD-Eintrag
ord-f1585dcd448b4369af4961eefd07158f
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08691788B2

Verknüpfte Notizen

Wird geladen…