Chlorotrimethylsilane → HCID 136352430, compound

HRID 1634918Notes

Reaction equation

HRID 1634918 reaction equation
[NH2:1][C:2]1[NH:3][C:4](=[O:12])[C:5]2[S:10][C:9](=[O:11])[NH:8][C:6]=2[N:7]=1.C[Si](C)(C)Cl.O([Si](C)(C)C)S(C(F)(F)F)(=O)=O.C(O[CH:34]1[O:40][C@@H:39]([CH2:41][O:42][C:43](=[O:50])[C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[C@:37]([C:51](=[O:58])[C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)([OH:38])[C@:35]1([C:59](=[O:66])[C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1)[OH:36])(=O)C.C(=O)(O)[O-].[Na+]>C(#N)C.C[Si](C)(C)N[Si](C)(C)C.C(OCC)(=O)C.O>[NH2:1][C:2]1[NH:3][C:4](=[O:12])[C:5]2[S:10][C:9](=[O:11])[N:8]([C@H:34]3[O:40][C@@H:39]([CH2:41][O:42][C:43](=[O:50])[C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=4)[C@:37]([C:51](=[O:58])[C:52]4[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=4)([OH:38])[C@:35]3([C:59](=[O:66])[C:60]3[CH:61]=[CH:62][CH:63]=[CH:64][CH:65]=3)[OH:36])[C:6]=2[N:7]=1

Participants

10

Reactant 5

HCID 6397ChlorotrimethylsilaneHCID 65367Trimethylsilyl triflate2×HCID 516892Sodium BicarbonateHCID 86585187HCID 86585187, compoundHCID 1357436395-Aminothiazolo[4,5-d]pyrimidine-2,7(3H,6H)-dione

Product 1

HCID 136352430HCID 136352430, compoundYield 76.7%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6342AcetonitrileSolvent3×HCID 8857Ethyl AcetateSolventHCID 13838HexamethyldisilazaneSolvent

Procedure

5-Aminothiazolo[4,5-d]pyrimidine-2,7(6H)-dione 32 (400 mg, 2.71 mmol) was suspended in acetonitrile (16 mL) and hexamethyldisilazane (0.96 mL), and trimethylchlorosilane (0.55 mL) and trimethylsilyl triflate (0.9 mL) added. The mixture was stirred under reflux for 3.5 h. A solution of trimethylsilyl triflate (0.45 mL) in acetonitrile (1.0 mL) was added dropwise and stirring and heating was continued for additional 30 min. A slurry of 1-O-acetyl-2,3,5-O-tribenzoyl-L-ribofuranose (1.22 g, 2.28 mmol) in acetonitrile (4.1 mL) was added and the mixture stirred under reflux for 30 min. The reaction mixture was cooled and slowly poured into a vigorously stirred mixture of sodium bicarbonate (2.81 g) and water (96 mL), which produced a stick solid. Ethyl acetate was added, the mixture stirred until the solid dissolved. The aqueous layer was extracted with ethyl acetate twice and the combined organic layer washed with sodium bicarbonate, dried (Na2SO4), and concentrated. The crude was purified by chromatography on silica with 5%Et3N and 5% ethanol in methylene chloride to give 1.10 g of 5-amino-3-(2′,3′,5′-O-tribenzoyl-β-L-ribofuranosyl)thiazolo[4,5-d]pyrimidine-2,7(6H)-dione 33 as a white solid.

Workup

  1. temperatureunder reflux for 3.5 h
  2. stirringstirring
  3. temperatureheating
  4. stirringthe mixture stirred
  5. temperatureunder reflux for 30 min
  6. temperatureThe reaction mixture was cooled
  7. customproduced a stick solid
  8. stirringthe mixture stirred until the solid
  9. dissolutiondissolved
  10. extractionThe aqueous layer was extracted with ethyl acetate twice
  11. washthe combined organic layer washed with sodium bicarbonate
  12. dry with materialdried (Na2SO4)
  13. concentrationconcentrated
  14. customThe crude was purified by chromatography on silica with 5%Et3N and 5% ethanol in methylene chloride

Sources & evidence

ORD record
ord-f94fa7b52b044ea380f0c3a8f9694155
Source dataset
uspto-grants-2003_01
Patent number
US06509320B1

Reaction notes

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