1,8-Diazabicyclo(5.4.0)undec-7-ene → 3-[3-(6-Methoxy-m-tolyl)-1,2-benzisothiazol-5-yl)-6-(trifluoromethyl)-2,4(1H,3H)-pyrimidinedione
Reaction equation
C(O[C:4]([NH:6]/[C:7](/[C:14]([F:17])([F:16])[F:15])=[CH:8]\[C:9]([O:11]CC)=O)=[O:5])C.[NH2:18][C:19]1[CH:20]=[CH:21][C:22]2[S:26][N:25]=[C:24]([C:27]3[CH:28]=[C:29]([CH3:35])[C:30]([O:33][CH3:34])=[CH:31][CH:32]=3)[C:23]=2[CH:36]=1.N12CCCN=C1CCCCC2>C1(C)C(C)=CC=CC=1>[CH3:34][O:33][C:30]1[C:29]([CH3:35])=[CH:28][C:27]([C:24]2[C:23]3[CH:36]=[C:19]([N:18]4[C:9](=[O:11])[CH:8]=[C:7]([C:14]([F:15])([F:16])[F:17])[NH:6][C:4]4=[O:5])[CH:20]=[CH:21][C:22]=3[S:26][N:25]=2)=[CH:32][CH:31]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
A mixture of ethyl 3-[(ethoxycarbonyl)amino]-4,4,4-trifluorocrotonate, (Z)-(2.04 g, 8 mmol), 5-amino-3-(6-methoxy-m-tolyl)-1,2-benzisothiazole (2.59 g, 9.6 mmol) and 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU, 1.46 g, 9.6 mmol) in xylene (15 mL) is heated at 110° C. for 6 hours, cooled, and quenched with ethyl acetate and water. The resultant mixture is extracted with ethyl acetate. The organic extracts are combined, washed with aqueous 2 N hydrochloric acid, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to obtain a foam. Flash chromatography of the foam using silica gel and a 3:7 ethyl acetate/hexanes solution gives the title product as a solid (2.5 g, 72% yield) which is identified by 1H and 19F NMR spectral analyses.
Workup
- temperaturecooled
- customquenched with ethyl acetate and water
- extractionThe resultant mixture is extracted with ethyl acetate
- washwashed with aqueous 2 N hydrochloric acid
- dry with materialdried over anhydrous sodium sulfate
- filtrationfiltered
- concentrationconcentrated in vacuo
- customto obtain a foam
Sources & evidence
- ORD record
- ord-feda41e2792f4755afcd05c724495655
- Source dataset
- uspto-grants-2001_11
- Patent number
- US06313295B1
Reaction notes
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