Oxalyl chloride → 1-Methyl-6-(trifluoromethyl)-3-(3-valeryl-1,2-benzisothiazol-5-yl)-2,4(1H,3H)-pyrimidinedione

HRID 1274642Notes

Reaction equation

HRID 1274642 reaction equation
[CH3:1][N:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][C:5](=[O:12])[N:4]([C:13]2[CH:14]=[CH:15][C:16]3[S:20][N:19]=[C:18]([C:21]([OH:23])=O)[C:17]=3[CH:24]=2)[C:3]1=[O:25].C(Cl)(=O)C(Cl)=O.[Cu](C#N)C#N.[CH2:37]([Li])[CH2:38][CH2:39][CH3:40]>C(Cl)Cl.CN(C)C=O.O1CCCC1>[CH3:1][N:2]1[C:7]([C:8]([F:11])([F:9])[F:10])=[CH:6][C:5](=[O:12])[N:4]([C:13]2[CH:14]=[CH:15][C:16]3[S:20][N:19]=[C:18]([C:21](=[O:23])[CH2:37][CH2:38][CH2:39][CH3:40])[C:17]=3[CH:24]=2)[C:3]1=[O:25]

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 111878605-[3,6-Dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-1,2-benzisothiazole-3-carboxylic acidHCID 178418260HCID 178418260, compoundHCID 178418339Butyllithium

Product 1

HCID 113044461-Methyl-6-(trifluoromethyl)-3-(3-valeryl-1,2-benzisothiazol-5-yl)-2,4(1H,3H)-pyrimidinedioneYield 64%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-1,2-benzisothiazole-3-carboxylic acid (0.200 g, 0.000540 mol) in methylene chloride is added N,N-dimethylformamide (one drop) followed by oxalyl chloride in methylene chloride (2.0 M, 0.540 ml, 0.00108 mol). The resultant mixture is stirred at room temperature for 90 minutes and concentrated in vacuo to a white solid, which is saved. To a suspension of copper cyanide (0.061 g, 0.000675 mol) in tetrahydrofuran, is added dropwise n-butyllithium (2.5 M in hexanes, 0.540 ml, 0.00135 mol) at -78° C. The reaction mixture is allowed to warm for 5 minutes and then cooled back to -78° C. The mixture is then treated with a solution of the white solid from the first step in tetrahydrofuran, and the resultant mixture stirred one hour at -78° C. The reaction mixture is quenched with saturated ammonium chloride and diluted with ethyl acetate. The organic layer is washed sequentially with saturated ammonium chloride, water and brine, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to a yellow syrup. Chromatography of the syrup on silica gel using hexanes:ethyl acetate gives the title compound as a colorless syrup (0.142 g, 64.0%) which is identified by NMR spectral analysis.

Workup

  1. concentrationconcentrated in vacuo to a white solid, which
  2. temperatureto warm for 5 minutes
  3. customThe reaction mixture is quenched with saturated ammonium chloride
  4. additiondiluted with ethyl acetate
  5. washThe organic layer is washed sequentially with saturated ammonium chloride, water and brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo to a yellow syrup

Sources & evidence

ORD record
ord-6897373544114904b6d6e9854c01d1b5
Source dataset
uspto-grants-2000_12
Patent number
US06156700

Reaction notes

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