Thymidine → HCID 18649770, compound

HRID 2081784Notes

Reaction equation

HRID 2081784 reaction equation
[CH:1]1([CH2:4][NH:5][C:6]2[N:14]=[CH:13][N:12]=[C:11]3[C:7]=2[NH:8][CH:9]=[N:10]3)[CH2:3][CH2:2]1.[C@@H:15]1(N2C=C(C)C(=O)NC2=O)[O:21][C@H:18]([CH2:19][OH:20])[CH2:17][CH2:16]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)C=O>[CH:1]1([CH2:4][NH:5][C:6]2[N:14]=[CH:13][N:12]=[C:11]3[C:7]=2[NH:8][CH:9]=[N:10]3)[CH2:2][CH2:3]1.[CH:1]1([CH2:4][NH:5][C:6]2[N:14]=[CH:13][N:12]=[C:11]3[C:7]=2[N:8]=[CH:9][N:10]3[C@H:15]2[CH2:16][CH2:17][C@@H:18]([CH2:19][OH:20])[O:21]2)[CH2:2][CH2:3]1

Participants

8

Reactant 5

HCID 5789ThymidineHCID 62657Potassium Phosphate, TribasicHCID 651192',3'-DideoxythymidineHCID 3362547N-(cyclopropylmethyl)-7H-purin-6-amineHCID 10290740Potassium azide

Product 2

HCID 3362547N-(cyclopropylmethyl)-7H-purin-6-amineHCID 18649770HCID 18649770, compoundYield 154%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
35 °C

Procedure

6-(Cyclopropylmethylamino)purine was prepared by nucleophilic displacement of the chlorine group on 6-chloropurine (Sigma Chemicals. St. Louis, Mo.) by the amino group on cyclopropylmethylamine (Karl Industries, Aurora, Ohio). 6-(Cyclopropylmethylamino)purine (2.64 mmol, 0.50 g) was dissolved in 5 mL of dimethylformamide with heating. After cooling to room temperature 3'-deoxythymidine (3.98 mmol, 0.90 g) (Horwitz J. P. et al., J. Org. Chem. 31, 205 (1966)) was added along with 30 mL of 10 mM potassium phosphate buffer with a pH of 6.8 containing 0.04% potassium azide. Purified thymidine phosphorylase (10,000 I.U.) and purine nucleoside phosphorylase (20,000 I. U.) (Krenitsky T. A. et al., Biochemistry 20, 3615, 1981 and U.S. Pat. No. 4,381,4440 absorbed onto 10 mL DEAE cellulose (Whatman) were added, and the suspension was stirred at 35° C. After 8 hours the reaction was filtered, and the filtrate was applied to a series of coupled columns. The initial column contained AG1-X 2 resin (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 500 mL water and the product was eluted with methanol. The product was then flash chromatographed on a silica gel column, 5×20 cm, with a mixture of chloroform:methanol (9:1, v/v). Solvent was removed in vacuo and the product gum was transferred in acetone to a vial. Lyophilization yielded 0.588 g of 6-(cyclopropylmethylamino)-9-((2R,5S)-tetrahydro-5-(hydroxymethyl)-2-furyl)-9H-purine, that analysed for 0.15 water and 0.15 acetone.

Workup

  1. temperaturewith heating
  2. custom4,381,4440 absorbed onto 10 mL DEAE cellulose (Whatman)
  3. additionwere added
  4. filtrationAfter 8 hours the reaction was filtered
  5. washAfter sample application, the columns were washed with 500 mL water
  6. washthe product was eluted with methanol
  7. customflash chromatographed on a silica gel column, 5×20 cm, with a mixture of chloroform:methanol (9:1
  8. customSolvent was removed in vacuo

Sources & evidence

ORD record
ord-2749df9807fa41829b4799669e827190
Source dataset
uspto-grants-1993_02
Patent number
US05185437

Reaction notes

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