N,O-bis(trimethylsilyl)acetamide → HCID 89975754, compound

HRID 1508624Notes

Reaction equation

HRID 1508624 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]([Cl:36])=[CH:32][CH:31]=2)[C@@H:24]([CH2:37][O:38][CH2:39][C:40]2[CH:45]=[CH:44][C:43]([Cl: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:35]=[CH:34][C:33]([Cl:36])=[CH:32][CH:31]=3)[C@@H:24]([CH2:37][O:38][CH2:39][C:40]3[CH:41]=[CH:42][C:43]([Cl: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 89975764HCID 89975764, compoundHCID 178418229Cytosine

Product 1

HCID 89975754HCID 89975754, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
80 °C

Procedure

To another reaction vessel, 0.12 g of cytosine and 0.53 mL of N,O-bis(trimethylsilyl)acetamide were added in a nitrogen atmosphere, and the obtained mixture was then stirred at 80° C. for 2 hours. After cooling in air, a methylene chloride solution containing (3S,4S,5R)-2-bromo-4-((4-chlorobenzyl)oxy)-5-(((4-chlorobenzyl)oxy)methyl)-3-fluorothiolane was added to the reaction mixture, and the obtained mixture was then stirred 60° C. for 2 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 sodium 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 80/20), so as to obtain 0.18 g of (3S,4S,5R)-2-(4-amino-2-oxo-1,2-dihydropyrimidin-1-yl)-4-((4-chlorobenzyl)oxy)-5-(((4-chlorobenzyl)oxy)methyl)-3-fluorothiolane 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 60° C. for 2 hours
  4. washthe thus obtained mixture was washed with a saturated sodium hydrogen carbonate aqueous solution
  5. dry with materialwas then dried over anhydrous sodium 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 80/20)

Sources & evidence

ORD record
ord-5d85fa26b4ff4d1f9dd6e6f66a34abcf
Source dataset
uspto-grants-2015_12
Patent number
US09221865B2

Reaction notes

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