Water → 2-Amino-6-methoxy-9-(5-O-propionyl-beta-D-arabinofuranosyl)-9H-purine

HRID 399383

Reaktionsgleichung

Reaktionsgleichung von HRID 399383
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[O:17][C@H:16]([CH2:18][OH:19])[C@@H:14]([OH:15])[C@@H:12]2[OH:13])=[C:4]([O:20][CH3:21])[N:3]=1.O.[C:23](OCC(Cl)(Cl)Cl)(=[O:26])[CH2:24][CH3:25]>N1C=CC=CC=1>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[O:17][C@H:16]([CH2:18][O:19][C:23](=[O:26])[CH2:24][CH3:25])[C@@H:14]([OH:15])[C@@H:12]2[OH:13])=[C:4]([O:20][CH3:21])[N:3]=1

Komponenten

5

Edukt 3

HCID 962WaterHCID 5271512,2,2-Trichloroethyl propionateHCID 3011155Nelarabine

Produkt 1

HCID 536401282-Amino-6-methoxy-9-(5-O-propionyl-beta-D-arabinofuranosyl)-9H-purine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1049PyridineLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

2-Amino-6-methoxy-9-(β-D-arabinofuranosyl)-9H-purine (1.0 g, 3.3 mmol) (prepared as described in European Patent Application No. 294 114) was suspended in 40 ml of pyridine that contained 300 μL of H2O and 2 ml of trichloroethyl propionate (Trichloroethyl propionate was synthesized by addition of 19 ml of propionyl chloride (Aldrich) over 30 minutes to 19.1 ml of trichlorethanol (Aldrich) in 40 ml of pyridine at 0° C.). The product was purified by successive washing with 2×100 ml aliquots of H2O, 5% NaHCO3, and H2O. 1H-NMR (200 MHz, CDCl3, 4.74 (s, 2H, Cl3CH2-), 2.49 (q, 2H, J=7.6 Hz, CH3CH2CO2-), 1.21 (t, 3H, J=7.6 Hz, CH3CH2 CO2-). The reaction was initiated with 0.100 g of subtilisin (Sigma Chemical Co., St. Louis, Mo., P-5380, lot No. 38F-0356), which had been activated by dissolving 1 g of the enzyme in 20 ml of 0.1M potassium phosphate at pH 7.8 and lyophilizing to dryness. After stirring for 23 hours at 40° C., the reaction was quenched by filtering off the enzyme and the solvent was removed in vacuo. The crude product was purified by chromatography on a 4.5×25 cm silica gel column with CH2Cl2 :CH3OH (9:1) as eluant. Product fractions were pooled and lyophilized from water to yield 0.76 g of the desired product as a white powder: m.p. 124° C.; TLC Rf =0.43 (silica gel; CH2Cl2 :CH3OH (9:1); UVλmax (ε, mM-1 cm-1) at pH 7.0, 278 nm (9.5).

Aufarbeitung

  1. customThe product was purified
  2. washby successive washing with 2×100 ml aliquots of H2O, 5% NaHCO3, and H2O
  3. dissolutionby dissolving 1 g of the enzyme in 20 ml of 0.1M potassium phosphate at pH 7.8
  4. customthe reaction was quenched
  5. filtrationby filtering off the enzyme
  6. customthe solvent was removed in vacuo
  7. customThe crude product was purified by chromatography on a 4.5×25 cm silica gel column with CH2Cl2 :CH3OH (9:1) as eluant

Quellen und Nachweise

ORD-Eintrag
ord-3652c7f1303843e98da45452775ec0f0
Quelldatensatz
uspto-grants-1998_10
Patentnummer
US05821236

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