Hydrochloric Acid → 5-[3,6-Dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-1,2-benzisothiazole-3-malononitrile

HRID 1274596Notes

Reaction equation

HRID 1274596 reaction equation
Cl[C:2]1[C:6]2[CH:7]=[C:8]([N:11]3[C:16](=[O:17])[CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[N:13]([CH3:22])[C:12]3=[O:23])[CH:9]=[CH:10][C:5]=2[S:4][N:3]=1.[C:24](#[N:28])[CH2:25][C:26]#[N:27].C(N(CC)CC)C.Cl>CS(C)=O.O.[Cl-].[Na+].O>[CH3:22][N:13]1[C:14]([C:18]([F:21])([F:20])[F:19])=[CH:15][C:16](=[O:17])[N:11]([C:8]2[CH:9]=[CH:10][C:5]3[S:4][N:3]=[C:2]([CH:25]([C:24]#[N:28])[C:26]#[N:27])[C:6]=3[CH:7]=2)[C:12]1=[O:23]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8010MalononitrileHCID 8471TriethylamineHCID 159065613-(3-chloro-1,2-benzisothiazol-5-yl)-1-methyl-6-(trifluoromethyl)-2,4(1H,3H)-pyrimidinedione

Product 1

HCID 221198185-[3,6-Dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-1,2-benzisothiazole-3-malononitrile

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 3-(3-chloro-1,2-benzisothiazol-5-yl)-1-methyl-6-(trifluoromethyl)-2,4(1H,3H)-pyrimidinedione (0.500 g), malononitrile (0.270 g) and triethylamine (1.50 g) in methyl sulfoxide is stirred at 60° C. for 15 minutes, cooled to room temperature, and diluted with water. The resultant aqueous mixture is extracted with ethyl acetate. The organic extract is washed with water, dried over anhydrous magnesium sulfate, and concentrated in vacuo to obtain a brown oil. The extracted aqueous phase is diluted with brine, acidified with concentrated hydrochloric acid, and extracted with ethyl acetate. The organic extract is dried over anhydrous magnesium sulfate and concentrated in vacuo to obtain a brown oil. Flash column chromatography of the combined oils using silica gel and an ethyl acetate/hexanes/methanol/acetic acid solution (10:10:4:1) gives the title product as an oil which is identified by NMR spectral analyses.

Workup

  1. temperaturecooled to room temperature
  2. extractionThe resultant aqueous mixture is extracted with ethyl acetate
  3. extractionThe organic extract
  4. washis washed with water
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customto obtain a brown oil
  8. extractionextracted with ethyl acetate
  9. extractionThe organic extract
  10. dry with materialis dried over anhydrous magnesium sulfate
  11. concentrationconcentrated in vacuo
  12. customto obtain a brown oil

Sources & evidence

ORD record
ord-77c1697c4d29451f9e9cfebf02970e39
Source dataset
uspto-grants-2000_12
Patent number
US06156700

Reaction notes

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