Adenine → (2R,3R)-1-Benzyloxy-3-(tert-butyldimethylsiloxy)-2-((6-amino-9H-purin-9-yl)methyl)butane

HRID 1754598Notes

Reaction equation

HRID 1754598 reaction equation
[N:1]1[C:9]([NH2:10])=[C:8]2[C:4]([N:5]=[CH:6][NH:7]2)=[N:3][CH:2]=1.CC1C=CC(S(O[CH2:22][C@@H:23]([CH2:34][O:35][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C@H:24]([O:26][Si:27]([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28])[CH3:25])(=O)=O)=CC=1>CN(C=O)C>[CH2:36]([O:35][CH2:34][C@@H:23]([CH2:22][N:5]1[CH:6]=[N:7][C:8]2[C:4]1=[N:3][CH:2]=[N:1][C:9]=2[NH2:10])[C@H:24]([O:26][Si:27]([C:30]([CH3:31])([CH3:33])[CH3:32])([CH3:28])[CH3:29])[CH3:25])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1

Participants

4

Reactant 2

HCID 190AdenineHCID 90411475HCID 90411475, compound

Product 1

HCID 90411857(2R,3R)-1-Benzyloxy-3-(tert-butyldimethylsiloxy)-2-((6-amino-9H-purin-9-yl)methyl)butaneYield 37%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
100 °C

Procedure

To a suspension of adenine (1.22 g, 9.1 mmol) in 25 ml of anhydrous DMF was added 2.96 g of Ce2CO3 (hydrate) and the mixture was stirred at 100° C. for 15 min. A solution of 9 (2.9 g, ˜7.4 mmol) in 20 ml of DMF was added in one portion. The reaction was stirred at 100° C. for 4 hrs until no starting material was found by HPLC, then cooled and filtered to remove unreacted adenine and cesium salts. The filtrate was concentrated, re-dissolved in ethyl acetate, washed with water, saturated NaCl and dried under Na2SO4. The crude product obtained after solvent evaporation was chromatographed on silica eluting with a gradient of acetone (20-35%) in ethyl acetate. Concentration of the pure product fractions and drying in vacuo afforded 1.2 g (37%) of 10 as a pale yellow viscous syrup. 1H NMR (CDCl3): δ 8.32 (s, 1H), 7.70 (s, 1H), 7.24 (m, 5H), 5.64 (s, 2H), 4.38 (m, 1H), 4.34 (d, 8.1 Hz, 2H), 4.16 (m, 1H), 4.02 (m, 1H), 3.32 (m, 2H), 2.23 (m, 1H), 1.14 (d, J=6.3 Hz, 3H), 0.85 (s, 9H), 0.015 (s, 3H), 0.00 (s, 3H).

Workup

  1. stirringThe reaction was stirred at 100° C. for 4 hrs until no starting material
  2. temperaturecooled
  3. filtrationfiltered
  4. customto remove unreacted adenine and cesium salts
  5. concentrationThe filtrate was concentrated
  6. dissolutionre-dissolved in ethyl acetate
  7. washwashed with water, saturated NaCl
  8. customdried under Na2SO4
  9. customThe crude product obtained
  10. customafter solvent evaporation
  11. customwas chromatographed on silica eluting with a gradient of acetone (20-35%) in ethyl acetate
  12. customConcentration of the pure product fractions and drying in vacuo

Sources & evidence

ORD record
ord-20a8a7425c0d4783acc8965fef7503f1
Source dataset
uspto-grants-2015_10
Patent number
US09169256B2

Reaction notes

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