Pyridine → 6-Deoxypenciclovir

HRID 5872

Reaktionsgleichung

Reaktionsgleichung von HRID 5872
P(Cl)(Cl)(Cl)=O.[OH:6][CH2:7][CH:8]([CH2:42][OH:43])[CH2:9][CH2:10][N:11]1[C:19](NC(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=[N:18][C:17]2[C:12]1=[N:13][C:14](OC)=[N:15][CH:16]=2.C(=O)(O)[O-].[Na+].[N:49]1C=CC=CC=1>O>[NH2:49][C:14]1[N:13]=[C:12]2[C:17]([N:18]=[CH:19][N:11]2[CH2:10][CH2:9][CH:8]([CH2:7][OH:6])[CH2:42][OH:43])=[CH:16][N:15]=1

Komponenten

6

Edukt 4

HCID 1049Pyridine2×HCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 678619439-(4-Hydroxy-3-hydroxymethylbut-1-yl)-2-monomethoxytritylaminopurine

Produkt 1

HCID 1285176-Deoxypenciclovir

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Versuchsvorschrift

To an ice-cooled solution of phosphorus oxychloride (93 μl, 1.0 mmol) in pyridine (2 ml) was added dropwise over 45 minutes a solution of 9-(4-hydroxy-3-hydroxymethylbut-1-yl)-2-monomethoxytritylaminopurine (0.46 g, 0.9 mmol) in pyridine (4 ml). The solution was stirred for a further 20 minutes at room temperature and was then added dropwise to a solution of sodium bicarbonate (0.34 g, 4.0 mmol) in water (6 ml). The solvent was removed and the residue was taken up in 80% acetic acid (9 ml) and the solution was stirred at 70° for 25 minutes. The solvent was removed and the residue was taken up in water and brought to pH 6 by addition of ammonia. The solution was extracted twice with chloroform and the solvent was removed. The residue was purified by preparative high pressure liquid chromatography on a C18 reverse-phase μ-Bondapack column eluting with 4% methanol in ammonium acetate buffer (pH 4.5, 50 mM) to afford 2-amino-9-(4-hydroxy-3-hydroxymethylbut-1-yl) purine 4':4"-phosphate as a white powder (225 mg, 75%); λmax (H2O) 220, 242, and 303 nm; νmax (KBr) 2900-3200 (br), 1705, 1615, and 1580 cm-1 ; δH [(CD3)2SO] 1.63 (1H, m, 3'-H), 1.74 (2H, q, J 7.0 Hz, 2'-H), 3.80 (2H, q, J 9.2 Hz, 2×Hax), 3.98 (2H, ddd, J 14.3, 10.9, and 3.5 Hz, 2×Heq), 4.08 (2H, t, J 7.1 Hz, 1'-H), 6.51 (2H, s, D2O exchangeable, 2-NH2), 8.10 (1H, s, 8-H), and 8.56 (1H, s, 6-H); (Found: C, 36.41; H, 5.18; N, 22.38%. C10H14N5O4P.0.3 NH3. 1.5H2O requires C, 36.25; H, 5.45; N, 22.40%).

Aufarbeitung

  1. customThe solvent was removed
  2. stirringthe solution was stirred at 70° for 25 minutes
  3. customThe solvent was removed
  4. additionbrought to pH 6 by addition of ammonia
  5. extractionThe solution was extracted twice with chloroform
  6. customthe solvent was removed
  7. customThe residue was purified by preparative high pressure liquid chromatography on a C18 reverse-phase μ-Bondapack column
  8. washeluting with 4% methanol in ammonium acetate buffer (pH 4.5, 50 mM)

Quellen und Nachweise

ORD-Eintrag
ord-1f2cecd09ef940538b1511536d172b39
Quelldatensatz
uspto-grants-1993_09
Patentnummer
US05246937

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