Methanol → HCID 15894273, compound

HRID 1871241Notes

Reaction equation

HRID 1871241 reaction equation
C([O:8][C@@H:9]1[C@@H:13]([CH2:14][O:15][Si](C(C)(C)C)(C2C=CC=CC=2)C2C=CC=CC=2)[S:12][CH:11]([N:33]2[CH:41]=[N:40][C:39]3[C:34]2=[N:35][C:36]([Cl:43])=[N:37][C:38]=3Cl)[C@H:10]1[F:44])C1C=CC=CC=1.ClB(Cl)Cl.CO.C(=O)([O-])O.[Na+].[NH3:56].C(O)C>C(Cl)Cl>[F:44][C@H:10]1[C@H:9]([OH:8])[C@@H:13]([CH2:14][OH:15])[S:12][C@H:11]1[N:33]1[CH:41]=[N:40][C:39]2[C:34]1=[N:35][C:36]([Cl:43])=[N:37][C:38]=2[NH2:56]

Participants

7

Reactant 5

HCID 887MethanolHCID 25135Boron TrichlorideHCID 516892Sodium BicarbonateHCID 21970069HCID 21970069, compoundHCID 22020343Ethanol, reaction products with ammonia, distn. residues

Product 1

HCID 15894273HCID 15894273, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

360 mg of the 9-(3-O-benzyl-5-O-t-butyldiphenylsilyl-2-deoxy-2-fluoro-4-thio-D-arabinofuranosyl)-2,6-dichloropurine was dissolved in 11 ml of methylene chloride. To this solution, 2.70 ml of 1 M trichloroboran was added dropwise at -78° C. under a stream of argon. The mixture was allowed to warm up to room temperature, and then stirred for 30 minutes. To this was added 1.0 ml of methanol at -78° C. The resulting mixture was stirred for a further 30 minutes, and then allowed to warm up to room temperature. To this mixture was added a saturated aqueous solution of sodium hydrogencarbonate. The solvent was distilled off, and the residue was azeotropically distilled with methanol three times. The residue was then separated into the alpha-anomer and the beta-anomer by silica gel column chromatography. 115 mg of the beta-anomer obtained was dissolved in 20 ml of a saturated ammonia/ethanol solution, and allowed to react in a sealed tube at 80° C. for 7 hours. The solvent was distilled off, and the residue was dissolved in 5 ml of DMF. To this solution was added 137 mg of ammonium fluoride, and the mixture was stirred at room temperature overnight. The solvent was distilled off, and the residue was purified by silica gel column chromatography to obtain 51 mg (yield 31%) of the title compound.

Workup

  1. stirringThe resulting mixture was stirred for a further 30 minutes
  2. temperatureto warm up to room temperature
  3. distillationThe solvent was distilled off
  4. distillationthe residue was azeotropically distilled with methanol three times
  5. customThe residue was then separated into the alpha-anomer
  6. custom115 mg of the beta-anomer obtained
  7. customto react in a sealed tube at 80° C. for 7 hours
  8. distillationThe solvent was distilled off
  9. dissolutionthe residue was dissolved in 5 ml of DMF
  10. additionTo this solution was added 137 mg of ammonium fluoride
  11. stirringthe mixture was stirred at room temperature overnight
  12. distillationThe solvent was distilled off
  13. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-3cb0edd7a73741989a38e1dcec04580e
Source dataset
uspto-grants-2000_08
Patent number
US06103707

Reaction notes

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