Thionyl Chloride → N-isopropyl-2-chloro-5-[3,6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1(2H)-pyrimidinyl]-4-fluorobenzamide

HRID 2051096Notes

Reaction equation

HRID 2051096 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([F:11])[C:8]([N:12]2[C:17](=[O:18])[CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[N:14]([CH3:23])[C:13]2=[O:24])=[CH:7][C:3]=1[C:4](O)=[O:5].S(Cl)(Cl)=O>C1C=CC=CC=1.CN(C)C=O>[CH:8]([NH:12][C:4](=[O:5])[C:3]1[CH:7]=[C:8]([N:12]2[C:17](=[O:18])[CH:16]=[C:15]([C:19]([F:20])([F:22])[F:21])[N:14]([CH3:23])[C:13]2=[O:24])[C:9]([F:11])=[CH:10][C:2]=1[Cl:1])([CH3:9])[CH3:7]

Participants

5

Reactant 2

HCID 24386Thionyl ChlorideHCID 120567892-Chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]benzoic acid

Product 1

HCID 19832700N-isopropyl-2-chloro-5-[3,6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1(2H)-pyrimidinyl]-4-fluorobenzamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 241BenzeneSolvent

Procedure

A mixture of 3.5 g of 2-chloro-5-[3,6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1(2H)-pyrimidinyl]-4-fluorobenzoic acid and 3.4 ml of thionyl chloride in 20 ml of benzene is heated to reflux temperature for 3 hours together with 2 drops of dimethylformamide. The mixture is then evaporated to dryness and the residue is dissolved in 15 ml of dioxan. The solution is added dropwise at room temperature to a solution of 0.7 g of isopropylamine and 1.1 g of pyridine in 15 ml of dioxan and the reaction mixture is stirred at room temperature for 2.5 hours. Subsequently, the mixture is treated with 400 ml of water, extracted twice with 400 ml of ethyl acetate each time, the organic phases are washed twice with 200 ml of 1N hydrochloric acid each time, thereafter twice with 200 ml of saturated sodium chloride solution each time, and the combined organic phases are dried over anhydrous sodium sulphate and evaporated. The residue is purified by chromatography on silica gel with ethyl acetate/n-hexane (1:2) as the eluent. In this manner there is obtained N-isopropyl-2-chloro-5-[3,6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1(2H)-pyrimidinyl]-4-fluorobenzamide which can be recrystallized from ethyl acetate/n-hexane. M.p. 146°-149° C.

Workup

  1. temperatureis heated
  2. customThe mixture is then evaporated to dryness
  3. dissolutionthe residue is dissolved in 15 ml of dioxan
  4. additionThe solution is added dropwise at room temperature to a solution of 0.7 g of isopropylamine and 1.1 g of pyridine in 15 ml of dioxan
  5. additionSubsequently, the mixture is treated with 400 ml of water
  6. extractionextracted twice with 400 ml of ethyl acetate each time
  7. washthe organic phases are washed twice with 200 ml of 1N hydrochloric acid each time
  8. dry with materialtwice with 200 ml of saturated sodium chloride solution each time, and the combined organic phases are dried over anhydrous sodium sulphate
  9. customevaporated
  10. customThe residue is purified by chromatography on silica gel with ethyl acetate/n-hexane (1:2) as the eluent

Sources & evidence

ORD record
ord-d6ef8dda3f644e39ba172135bae4f8fe
Source dataset
uspto-grants-1991_05
Patent number
US05017211

Reaction notes

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