Thymidine → HCID 9861413, compound

HRID 1683183Notes

Reaction equation

HRID 1683183 reaction equation
C1(N)CC1.[NH2:5][C:6]1[N:14]=[C:13]2[C:9]([N:10]=[CH:11][NH:12]2)=[C:8]([NH:15][CH:16]2[CH2:18][CH2:17]2)[N:7]=1.[F:19][C@@H:20]1[C@@H:24]([CH2:25][OH:26])[O:23][C@@H:22](N2C=C(C)C(=O)NC2=O)[CH2:21]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[N-]=[N+]=[N-].[K+].[C@@H]1(N2C=C(C)C(=O)NC2=O)O[C@H](CO)[C@@H](O)C1>CN(C=O)C.CS(C)=O>[NH2:5][C:6]1[N:14]=[C:13]2[C:9]([N:10]=[CH:11][NH:12]2)=[C:8]([NH:15][CH:16]2[CH2:18][CH2:17]2)[N:7]=1.[NH2:5][C:6]1[N:14]=[C:13]2[C:9]([N:10]=[CH:11][N:12]2[C@@H:22]2[O:23][C@H:24]([CH2:25][OH:26])[C@@H:20]([F:19])[CH2:21]2)=[C:8]([NH:15][CH:16]2[CH2:18][CH2:17]2)[N:7]=1

Participants

10

Reactant 6

HCID 5789ThymidineHCID 330393'-FluorothymidineHCID 62657Potassium Phosphate, TribasicHCID 69828CyclopropylamineHCID 10290740Potassium azideHCID 178508662HCID 178508662, compound

Product 2

HCID 9861413HCID 9861413, compoundYield 72.1%HCID 178508662HCID 178508662, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
37 °C

Procedure

2-Amino-6-(cyclopropylamino)-9H-purine was prepared by the displacement of the clorine group on 2-amino-6-chloropurine (Aldrich Chemical Company) by cyclopropylamine (Aldrich Chemical Company) 2-Amino-6-(cyclopropylamino)-9H-purine (0.50 g, 2.7 mmoles) was dissolved in DMF (5 ml) and DMSO (5 ml). 3'-Deoxy-3'-fluorothymidine (0.81 g, 3.3 mmoles) and potassium phosphate buffer (10 mM, 30 ml), pH 6.8, containing 0.04% potassium azide were added. Purified purine nucleoside phosphorylase (7500 I.U.) and thymidine phosphorylase (37.50 I.U.) adsorbed onto 5 ml DEAE-cellulose resin were added to the reaction and the suspension stirred at 37° C. After 23 days, the reaction was filtered and the filtrate applied to a series of coupled columns. The initial column contained AG1-X2 (OH-form, 2.5×10 cm) while the second column contained Amberlite XAD-2 resin (2.5×20 cm). After sample application, the columns were washed with water (700 ml) and the product eluted with methanol. Product-containing fractions were then flash chromatographed down a silica gel column (4.8×24 cm) using ethyl acetate:methanol (95:5) as eluant. The product was further purified by flash chromatography down a silica gel column (2.5×40 cm) using dichloromethane:methanol(9:1) as eluant. Solvent was evaporated in vacuo and lyophilisation yielded 0.30 g of 2-amino-6-(cyclopropyl-amino)-9-(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-9H-purine (33%): mp 75° C.;

Workup

  1. additionwere added
  2. additionwere added to the reaction
  3. filtrationthe reaction was filtered
  4. washAfter sample application, the columns were washed with water (700 ml)
  5. washthe product eluted with methanol
  6. customflash chromatographed down a silica gel column (4.8×24 cm)
  7. customThe product was further purified by flash chromatography down a silica gel column (2.5×40 cm)
  8. customSolvent was evaporated in vacuo and lyophilisation

Sources & evidence

ORD record
ord-d93c40cfc5364df5abfdb658ab91e313
Source dataset
uspto-grants-1997_06
Patent number
US05637574

Reaction notes

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