Thymidine → HCID 86751195, compound

HRID 1376470Notes

Reaction equation

HRID 1376470 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][NH:8]2)=[C:4]([NH:11][CH3:12])[N:3]=1.[F:13][C@@H:14]1[C@@H:18]([CH2:19][OH:20])[O:17][C@@H:16](N2C=CC(=O)NC2=O)[CH2:15]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+].CO>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:16]2[O:17][C@H:18]([CH2:19][OH:20])[C@@H:14]([F:13])[CH2:15]2)=[C:4]([NH:11][CH3:12])[N:3]=1

Participants

7

Reactant 4

HCID 5789ThymidineHCID 1624502',3'-Dideoxy-3'-fluorouridineHCID 10290740Potassium azideHCID 178482383HCID 178482383, compound

Product 1

HCID 86751195HCID 86751195, compoundYield 18%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 62657Potassium Phosphate, TribasicSolvent

Conditions

Temperature
45 °C

Procedure

2-Chloro-6-methylamino-9H-purine (0.48 g 2.6 moles) 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 9 days, 100 ml MeOH was added to the reaction mixture. The resulting mixture was filtered through Celite. The filtrate was flash chromatographed on silica gel (2.5×20 cm) with dichloromethane:methanol (96:4). Solvent was removed and lyophilization yielded 0.117 g of 2-chloro-9-(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-6-(methylamino)-9H-purine (18%): mp 181°-182° C.; TLC Rf 0.70 (silica ge, MeCN:15N NH4OH:H2O/85:5:10); [α]D20 -18.6 (c=0.5, DMF); UV λmax (ε×10-3) at pH 7, 269 (17.6); at pH 13, 269 (16.8); 1H NMR (400 MHz, DMSO-d6) δ8.35 (s, 1H, H8), 8.32 (b, 1H, NH), 6.30 (dd, 1H, H1', J=9.1 Hz, J=5.7 Hz), 5.41 (dd, 1H, H3', J=53.5 Hz, J=4.1 Hz), 5.16 (t, 1H, OH5', J=5.7 Hz), 4.16-4.24 (m, 1H, H4'), 3.57 (t, 2H, H5' and H5", J=5.2 Hz), 2.83-3.00 (m, 4H, NCH3 and H2') and 2.60-2.73 (m, 1H, H2"); MS (ci) 302 (M+1), 282 (M-F), 184 (MH2 --C5H8FO2).

Workup

  1. additionwas added
  2. filtrationThe resulting mixture was filtered through Celite
  3. customchromatographed on silica gel (2.5×20 cm) with dichloromethane:methanol (96:4)
  4. customSolvent was removed

Sources & evidence

ORD record
ord-7a7fd4d91b454d86889c3ba959e05c87
Source dataset
uspto-grants-1997_09
Patent number
US05663154

Reaction notes

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