Sodium hydride → HCID 25165952, compound

HRID 1643357Notes

Reaction equation

HRID 1643357 reaction equation
[CH2:1]([N:3]1[C:8]([C:9]([C:11]2[CH:12]=[C:13]([CH:16]=[C:17]([CH3:19])[CH:18]=2)[C:14]#[N:15])=[O:10])=[C:7]([CH:20]([CH3:22])[CH3:21])[C:6](=[O:23])[NH:5][C:4]1=[O:24])[CH3:2].[H-].[Na+].Br[CH2:28][O:29][C:30](=[O:32])[CH3:31]>CN(C=O)C.O>[C:30]([O:29][CH2:28][N:5]1[C:6](=[O:23])[C:7]([CH:20]([CH3:21])[CH3:22])=[C:8]([C:9](=[O:10])[C:11]2[CH:18]=[C:17]([CH3:19])[CH:16]=[C:13]([C:14]#[N:15])[CH:12]=2)[N:3]([CH2:1][CH3:2])[C:4]1=[O:24])(=[O:32])[CH3:31]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 68536Bromomethyl acetateHCID 25215428Ainuovirine

Product 1

HCID 25165952HCID 25165952, compoundYield 79%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-(3-ethyl-5-isopropyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carbonyl)-5-methylbenzonitrile (778 g, 2.39 mol) in anhydrous DMF (5 L) was added 60% NaH (115 g) portion-wise over 30 min at 0° C. The reaction mixture was stirred at room temperature for 3 hours and then the mixture was cooled to −10° C. Acetic acid bromomethyl ester (321 mL) was dropwise added to the reaction mixture for 2 hours at the same temperature and the reaction mixture was stirred at room temperature for 12 hours. The mixture was diluted with water (10 L). The precipitate was collected by filtration, washed with water (5 L) and then dissolved in dichloromethane (10 L). The organic solution was washed with water (4 L), dried with anhydrous magnesium sulfate (1 kg) and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: ethyl acetate/dichloromethane, 1:20) to give (4-(3-cyano-5-methylbenzoyl)-3-ethyl-5-isopropyl-2,6-dioxo-2,3-dihydropyrimidin-1(6H)-yl)methyl acetate (745 g, 1.87 mol, 79%) as a white solid.

Workup

  1. temperaturethe mixture was cooled to −10° C
  2. stirringthe reaction mixture was stirred at room temperature for 12 hours
  3. filtrationThe precipitate was collected by filtration
  4. washwashed with water (5 L)
  5. dissolutiondissolved in dichloromethane (10 L)
  6. washThe organic solution was washed with water (4 L)
  7. dry with materialdried with anhydrous magnesium sulfate (1 kg)
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was purified by silica gel column chromatography (eluent: ethyl acetate/dichloromethane, 1:20)

Sources & evidence

ORD record
ord-f1a32b26eff54c6ba77dc44d70a65af3
Source dataset
uspto-grants-2012_02
Patent number
US08119800B2

Reaction notes

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