Water → HCID 15476591, compound

HRID 1446034Notes

Reaction equation

HRID 1446034 reaction equation
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[O:23][C@H:22]([CH2:24][O:25][C:26](=[O:28])[CH3:27])[C@@H:17]([O:18][C:19](=[O:21])[CH3:20])[C@H:12]2[O:13][C:14](=[O:16])[CH3:15])=[C:4](Cl)[N:3]=1.Cl.[CH3:31][NH:32][CH3:33].C(N(C(C)C)CC)(C)C.O>N1C=CC=CC=1>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[O:23][C@H:22]([CH2:24][O:25][C:26](=[O:28])[CH3:27])[C@@H:17]([O:18][C:19](=[O:21])[CH3:20])[C@H:12]2[O:13][C:14](=[O:16])[CH3:15])=[C:4]([N:32]([CH3:33])[CH3:31])[N:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10473Dimethylamine, hydrochlorideHCID 81531DiisopropylethylamineHCID 10788628(2R,3R,4R,5R)-2-(Acetoxymethyl)-5-(2-amino-6-chloro-9H-purin-9-yl)tetrahydrofuran-3,4-diyl diacetate

Product 1

HCID 15476591HCID 15476591, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent2×

Procedure

2-amino-6-chloro-9-(2′,3′,5′-tri-O-acetyl-β-D-ribofuranosyl) purine (1) [M. J. Robins and B. Uznanski, Can. J. Chem., 59, 2601-2607 (1981)](18.6 mmol, 7.96 g) was dehydrated three times azeotropically with anhydrous pyridine, and dissolved in anhydrous pyridine, then dimethylamine hydrochloride (55.8 mmol, 4.55 g) and diisopropylethylamine (74.4 mmol) were added thereto with stirring at room temperature. The mixture was stirred at room temperature for 15 hours. After confirming completion of the reaction by TLC, water was added to the reaction mixture and concentrated in vacuo. Chloroform was added to the residue, and the organic layer was washed 3 times with water, 2 times with 5% aqueous sodium hydrogen carbonate, once with water and 2 times with 10% aqueous citrate solution, then the organic layer was dried with magnesium sulfate, and dried in vacuo after filtration. The residue was treated with azeotropic distillation with toluene until no odor of pyridine was noted, the product was purified by silica-gel chromatography (dichloromethane-ethanol) to obtain the product (2) 5.42 g (12.4 mmol) (67%). 1H-NMR (500.13 MHz, CDCl3) δ: 7.56 (s, 1H, H8), 6.02 (d, 1H, H1′, J=5.0 Hz), 5.95 (dd, 1H, H2′, J=5.0 Hz), 5.79 (t, 1H, H3′, J=5.0 Hz), 4.69 (s, 2H, 2-NH2), 4.42-4.45 (m, 1H, H4′), 4.34-4.40 (m, 2H, H5′, H5″), 3.43 (br, 6H, N—CH3), 2.13, 2.10, 2.08 (s, 3H, Ac).

Workup

  1. stirringThe mixture was stirred at room temperature for 15 hours
  2. additionwas added to the reaction mixture
  3. concentrationconcentrated in vacuo
  4. additionChloroform was added to the residue
  5. washthe organic layer was washed 3 times with water, 2 times with 5% aqueous sodium hydrogen carbonate
  6. dry with materialonce with water and 2 times with 10% aqueous citrate solution, then the organic layer was dried with magnesium sulfate
  7. customdried in vacuo
  8. filtrationafter filtration
  9. additionThe residue was treated with azeotropic distillation with toluene until no odor of pyridine
  10. customthe product was purified by silica-gel chromatography (dichloromethane-ethanol)

Sources & evidence

ORD record
ord-14a62c5000ab42df84e6fafc1fbc4f0f
Source dataset
uspto-grants-2010_02
Patent number
US07667031B2

Reaction notes

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