Ammonia → N-Benzoylcytidine

HRID 2117796Notes

Reaction equation

HRID 2117796 reaction equation
[C@@H:1]1([N:10]2[CH:17]=[CH:16][C:14]([NH2:15])=[N:13][C:11]2=[O:12])[O:9][C@H:6]([CH2:7][OH:8])[C@@H:4]([OH:5])[C@H:2]1[OH:3].C[Si](C)(C)Cl.[C:23](Cl)(=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.N>N1C=CC=CC=1.O>[C:23]([NH:15][C:14]1[CH:16]=[CH:17][N:10]([C@@H:1]2[O:9][C@H:6]([CH2:7][OH:8])[C@@H:4]([OH:5])[C@H:2]2[OH:3])[C:11](=[O:12])[N:13]=1)(=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

7

Reactant 4

HCID 222AmmoniaHCID 6175CytidineHCID 6397ChlorotrimethylsilaneHCID 7412Benzoyl chloride

Product 1

HCID 10066259N-BenzoylcytidineYield 96%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1049PyridineSolvent

Procedure

A suspension of cytidine (9.72 g, 40.0 mmol) in pyridine (200 ml) was added to trimethylchlorosilane (25.6 ml, 200 mmol). After 15 minutes of stirring, benzoyl chloride (23.2 ml, 200 mmol) was added, and the reaction was allowed to proceed at room temperature for 2 hours. The reaction mixture was then cooled on an ice bath, and water (40 ml) was added. Five minutes later, 28% aqueous ammonia (40 ml) was added, and the mixture was stirred at room temperature for 15 minutes. Then, the solvent was distilled off under reduced pressure, and acetone was added to precipitate a white solid. The precipitate was filtered off and recrystallized from water to give N4-benzoylcytidine (13.3 g, 96%). The N4-benzoylcytidine (13.0 g, 37.4 mmol), triphenylphosphine (28.0 g, 107 mmol) and lithium azide (13.0 g, 266 mmol) were suspended in dried DMA, and carbon tetrabromide (35.5 g, 107 mmol) was added to the suspension. After 3 hours of stirring at room temperature, ethyl acetate (1500 ml) was added, and the mixture was washed with water and a saturated aqueous solution of sodium chloride (1000 ml each). The organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was recrystallized from methanol to give 5′-azido-5′-deoxy-N4-benzoylcytidine (12.4 g, yield 89%). A solution of 5′-azido-5′-deoxy-N4-benzoylcytidine (10.0 g, 26.9 mmol) in methanol-DMF (1:1 v/v, 100 ml) was vigorously stirred with 10% palladium-on-carbon (about 1.0 g) in a hydrogen atmosphere. The resulting mixture was filtered, and the filtrate was evaporated under reduced pressure to give 5′-amino-5′-deoxy-N4-benzoylcyridine (9.04 g, yield 97%).

Workup

  1. waitto proceed at room temperature for 2 hours
  2. temperatureThe reaction mixture was then cooled on an ice bath
  3. stirringthe mixture was stirred at room temperature for 15 minutes
  4. distillationThen, the solvent was distilled off under reduced pressure, and acetone
  5. additionwas added
  6. customto precipitate a white solid
  7. filtrationThe precipitate was filtered off
  8. customrecrystallized from water

Sources & evidence

ORD record
ord-6500219c29e4419494b9dc03835642d5
Source dataset
uspto-grants-2008_10
Patent number
US07442788B2

Reaction notes

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