CID 533837 → 2-(2,6-Diaminopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol

HRID 841085Notes

Reaction equation

HRID 841085 reaction equation
O.[C@@H:2]1([N:11]2[C:21]3[N:20]=[C:18]([NH2:19])[NH:17][C:15](=O)[C:14]=3[N:13]=[CH:12]2)[O:10][C@H:7]([CH2:8][OH:9])[C@@H:5]([OH:6])[C@H:3]1[OH:4].[SiH3][NH:23][SiH3].FC(F)(F)S(O[SiH3])(=O)=O.C(O)(C)C.[OH-].[NH4+].O>CS(C)=O.CO.C1(C)C=CC=CC=1>[CH:12]1[N:11]([CH:2]2[O:10][CH:7]([CH2:8][OH:9])[CH:5]([OH:6])[CH:3]2[OH:4])[C:21]2[N:20]=[C:18]([NH2:19])[N:17]=[C:15]([NH2:23])[C:14]=2[N:13]=1

Participants

8

Reactant 4

HCID 533837CID 533837HCID 19893943isopropanol water NH4OHHCID 71401765Silyl trifluoromethanesulfonateHCID 135705230Guanosine Hydrate

Product 1

HCID 2220762-(2,6-Diaminopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
25 °C

Procedure

To a 2 L stainless steel Parr bomb was added guanosine hydrate (100 g, 0.35 mol, Aldrich), hexamethyl)disilazane (320 mL, 1.52 mol, 4.4 eq.), trimethyl)silyl triflouromethanesulfonate (8.2 mL), and toluene (350 mL). The bomb was sealed and partially submerged in an oil bath (170° C.; internal T 150° C., 150 psi) for 5 days. The bomb was cooled in a dry ice/acetone bath and opened. The contents were transferred with methanol (300 mL) to a flask and the solvent was evaporated under reduced pressure. Aqueous methanol (50%, 1.2 L) was added. The resulting brown suspension was heated to reflux for 5 h. The suspension was concentrated under reduced pressure to one half volume in order to remove most of the methanol. Water (600 mL) was added and the solution was heated to reflux, treated with charcoal (5 g) and hot filtered through Celite. The solution was allowed to cool to 25° C. The resulting precipitate was collected, washed with water (200 mL) and dried at 90° C./0.2 mmHg for 5 h to give a constant weight of 87.4 g (89%) of tan, crystalline solid; mp 247° C. (shrinks), 255° C. (dec, lit. (1) mp 250-252° C.); TLC homogenous (Rf 0.50, isopropanol-ammonium hydroxide-water 16:3:1); PMR (DMSO), δ5.73 (d,2, 2-NH2), 5.78 (s, 1, H-1), 6.83 (br s, 2, 6-NH2).

Workup

  1. customThe bomb was sealed
  2. custompartially submerged in an oil bath
  3. temperatureThe bomb was cooled in a dry ice/acetone bath
  4. customthe solvent was evaporated under reduced pressure
  5. additionAqueous methanol (50%, 1.2 L) was added
  6. temperatureThe resulting brown suspension was heated
  7. temperatureto reflux for 5 h
  8. concentrationThe suspension was concentrated under reduced pressure to one half volume in order
  9. customto remove most of the methanol
  10. additionWater (600 mL) was added
  11. temperaturethe solution was heated
  12. temperatureto reflux
  13. additiontreated with charcoal (5 g)
  14. filtrationhot filtered through Celite
  15. customThe resulting precipitate was collected
  16. washwashed with water (200 mL)
  17. customdried at 90° C./0.2 mmHg for 5 h
  18. customto give a constant weight of 87.4 g (89%) of tan, crystalline solid

Sources & evidence

ORD record
ord-dbc520ba827c41c9985621b5dfd6d1db
Source dataset
uspto-grants-2002_04
Patent number
US06369209B1

Reaction notes

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