N,O-bis(trimethylsilyl)acetamide → HCID 118108775, compound

HRID 716123Notes

Reaction equation

HRID 716123 reaction equation
[NH:1]1[CH:8]=[CH:7][C:5]([NH2:6])=[N:4][C:2]1=[O:3].C/C(/O[Si](C)(C)C)=N\[Si](C)(C)C.Br[CH:22]1[C@@H:26]([F:27])[C@H:25]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=2)[C@@H:24]([CH2:37][O:38][CH2:39][C:40]2[CH:45]=[CH:44][C:43]([CH3:46])=[CH:42][CH:41]=2)[S:23]1>C(Cl)Cl>[NH2:6][C:5]1[CH:7]=[CH:8][N:1]([CH:22]2[C@@H:26]([F:27])[C@H:25]([O:28][CH2:29][C:30]3[CH:31]=[CH:32][C:33]([CH3:36])=[CH:34][CH:35]=3)[C@@H:24]([CH2:37][O:38][CH2:39][C:40]3[CH:41]=[CH:42][C:43]([CH3:46])=[CH:44][CH:45]=3)[S:23]2)[C:2](=[O:3])[N:4]=1

Participants

5

Reactant 3

HCID 6913588N,O-bis(trimethylsilyl)acetamideHCID 89975543(3S,4S,5R)-2-bromo-3-fluoro-4-((4-methylbenzyl)oxy)-5-(((4-methylbenzyl)oxy)meth yl)thiolaneHCID 178418229Cytosine

Product 1

HCID 118108775HCID 118108775, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
80 °C

Procedure

To another reaction vessel, 0.10 g of cytosine and 0.58 mL of N,O-bis(trimethylsilyl)acetamide were added in a nitrogen atmosphere, and the obtained mixture was then stirred at 80° C. for 1.5 hours. After cooling in air, the methylene chloride solution containing (3S,4S,5R)-2-bromo-3-fluoro-4-((4-methylbenzyl)oxy)-5-(((4-methylbenzyl)oxy)meth yl)thiolane was added to the reaction mixture, and the obtained mixture was then stirred at 60° C. for 2.5 hours. Thereafter, methylene chloride was added to the reaction mixture, and the thus obtained mixture was washed with a saturated sodium hydrogen carbonate aqueous solution, and was then dried over anhydrous magnesium sulfate. After that, the solvent was distilled away under reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform/methanol=100/0 to 90/10), so as to obtain 72 mg of (3S,4S,5R)-2-(4-amino-2-oxo-1,2-dihydropyrimidin-1-yl)-3-fluoro-4-((4-methylbenzyl)oxy)-5-(((4-methylbenzyl)oxy)methyl)thiolane in the form of a light yellow solid.

Workup

  1. temperatureAfter cooling in air
  2. additionwas added to the reaction mixture
  3. stirringthe obtained mixture was then stirred at 60° C. for 2.5 hours
  4. washthe thus obtained mixture was washed with a saturated sodium hydrogen carbonate aqueous solution
  5. dry with materialwas then dried over anhydrous magnesium sulfate
  6. distillationAfter that, the solvent was distilled away under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography (chloroform/methanol=100/0 to 90/10)

Sources & evidence

ORD record
ord-edfb937bba2042928095f9029ed5bc37
Source dataset
uspto-grants-2015_11
Patent number
US09187514B2

Reaction notes

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