Dimethyl Sulfate → HCID 19745794, compound

HRID 2253581Notes

Reaction equation

HRID 2253581 reaction equation
[F:1][C:2]1[C:14]([N:15]2[C:20](=[O:21])[CH:19]=[C:18]([CH3:22])[NH:17][C:16]2=[O:23])=[CH:13][C:5]2[N:6]([CH2:10][C:11]#[CH:12])[C:7](=[O:9])[S:8][C:4]=2[CH:3]=1.[H-].[Na+].[H][H].S(OC)(O[CH3:32])(=O)=O>CN(C)C=O.O>[CH3:32][N:17]1[C:18]([CH3:22])=[CH:19][C:20](=[O:21])[N:15]([C:14]2[C:2]([F:1])=[CH:3][C:4]3[S:8][C:7](=[O:9])[N:6]([CH:10]=[C:11]=[CH2:12])[C:5]=3[CH:13]=2)[C:16]1=[O:23]

Participants

7

Reactant 4

HCID 6497Dimethyl SulfateHCID 24758Sodium hydrideHCID 19745810HCID 19745810, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 19745794HCID 19745794, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

A solution of 6.1 g of 3-[6-fluoro-2-oxo-3-(2-propynyl)-5-benzothiazolinyl]-6-methyl-2,4(1H,3H)-pyrimidinedione (see Example 4) in 50 ml of dimethylformamide is added while stirring to a suspension of 0.8 g of a 55% sodium hydride dispersion in 25 ml of dimethylformamide. After the hydrogen evolution has finished the mixture is treated with 2.8 g of dimethyl sulphate and stirred for one hour. Thereafter, the reaction mixture is poured into 500 ml of water, the aqueous mixture is extracted three times with 100 ml of ethyl acetate each time and the organic phase is dried over anhydrous sodium sulphate. The solvent is subsequently distilled off under reduced pressure and the thus-obtained residue (7.2 g) is purified by chromatography on a column of 350 g of aluminium oxide (Brockmann I) using methylene chloride/n-hexane (3:1) as the eluent. The first fraction (1.5 g) is recrystallized from ethyl acetate, whereby there is obtained 1,6-dimethyl-3-[6 -fluoro-2-oxo-3-(1,2-propanedienyl)-5-benzothiazolinyl]-2,4(1H,3H)-pyrimidinedione, m.p.>250° C. By further elution of the column with methylene chloride/ethyl acetate (3:1) there is obtained the second fraction (4.7 g) which is recrystallized from ethyl acetate. In this manner there is obtained 1,6-dimethyl-3-[6-fluoro-2-oxo-3-(2-propynyl)-5-benzothiazolinyl]-2,4(1H,3H)-pyrimidinedione, m.p. 180°-181° C.

Workup

  1. extractionthe aqueous mixture is extracted three times with 100 ml of ethyl acetate each time
  2. dry with materialthe organic phase is dried over anhydrous sodium sulphate
  3. distillationThe solvent is subsequently distilled off under reduced pressure
  4. customthe thus-obtained residue (7.2 g) is purified by chromatography on a column of 350 g of aluminium oxide (Brockmann I)
  5. customThe first fraction (1.5 g) is recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-00b29b85773a47a084ae7eeb789cbe67
Source dataset
uspto-grants-1993_08
Patent number
US05232898

Reaction notes

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