Thymidine → HCID 11550992, compound

HRID 1376473Notes

Reaction equation

HRID 1376473 reaction equation
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][NH:8]2)=[C:4]([Cl:11])[N:3]=1.[F:12][C@@H:13]1[C@@H:17]([CH2:18][OH:19])[O:16][C@@H:15](N2C=CC(=O)NC2=O)[CH2:14]1.[N-]=[N+]=[N-].[K+].[C@@H]1(N2C=C(C)C(=O)NC2=O)O[C@H](CO)[C@@H](O)C1>P([O-])([O-])([O-])=O.[K+].[K+].[K+]>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:15]2[O:16][C@H:17]([CH2:18][OH:19])[C@@H:13]([F:12])[CH2:14]2)=[C:4]([Cl:11])[N:3]=1

Participants

6

Reactant 4

HCID 5789ThymidineHCID 1624502',3'-Dideoxy-3'-fluorouridineHCID 10290740Potassium azideHCID 1785084356-chloro-1H-purin-2-amine

Product 1

HCID 11550992HCID 11550992, compoundYield 23.7%

Reagents, catalysts & solvents 1

HCID 62657Potassium Phosphate, TribasicSolvent

Conditions

Temperature
45 °C

Procedure

2-Amino-6-chloro-9H-purine (0.48 g, 2.8 mmoles), (Aldrich Chemical Company, Milwaukee, Wis.) and 2',3'-dideoxy-3'-fluorouridine (0.50 g, 2.2 mmoles) were suspended in 50 ml 10 mM potassium phosphate buffer, pH 7.0, containing 0.04% potassium azide. Purine nucleoside phosphorylase (1120 I.U.) and thymidine phosphorylase (10,000 I.U.) (Krenitsky, et al., Biochemistry, 20, 3615, 1981 and U.S. Pat. No. 4,381,344) immobilized on DEAE cellulose was added and the suspension was stirred at 45° C. After 2 days, the reaction mixture was filtered and solvent was removed in vacuo. The residue was flash chromatographed on silica gel (2.5×20 cm) with dichloromethane:methanol:acetone (96:2:2). Solvent was removed and lyophilization yielded 0.15 g of 2-amino-6-chloro-9-(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-purine (23%): mp 172° C.; [α]D20 -41.0 (c=0.5, DMF); UV λmax (ε×10-3) at pH 7, 308 (7.7); at pH 13, 303 (7.6); 1H NMR (300 MHz, DMSO-d6) δ8.36 (s, 1H, H8), 7.01 (s, 2H, NH2), 6.27 (dd, 1H, H1', J=9.0 Hz, J=5.8 Hz), 5.42 (dd, 1H, H3', J=53.8 HZ, J=4.4 Hz), 5.14 (t, 1H, OH5', J=5.4 Hz), 4.20 (dt, 1H, H4', J=26.5 Hz, J=4.8 Hz), 3.57 (t, 2H, H5' and H5", J=5.3 Hz), 2.63-3.04 (m, 2H, H2' and H2"); MS (ci) 288 (M+1), 268 (M-F), 70 (MH2 --C5H8FO2).

Workup

  1. additionwas added
  2. filtrationthe reaction mixture was filtered
  3. customsolvent was removed in vacuo
  4. customchromatographed on silica gel (2.5×20 cm) with dichloromethane:methanol:acetone (96:2:2)
  5. customSolvent was removed

Sources & evidence

ORD record
ord-4003a9218e704ae7ba2e1edeb2907e8a
Source dataset
uspto-grants-1997_09
Patent number
US05663154

Reaction notes

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