Reaction #1810840

Reaction equation

4-Amino-N-methyl-benzenesulphonamide

cyanamide

1-benzyl-5-(3-dimethylaminoprop-2-en-1-oyl)-2-methylimidazole

sodium methoxide

→

title compound

Yield 70.0%

4-(1-Benzyl-2-methylimidazol-5-yl)-2-[4-(N-methylsulphamoyl)anilino]pyrimidine

Yield 70.0%

Solvents

dimethylacetamide

MeOH

hydrogen chloride

Conditions

Workup

1. 1
   workup.ADDITIONadded
2. 2
   workup.ADDITIONwas added
3. 3
   Temperatureto cool
4. 4
   Temperaturethe mixture heated
5. 5
   Temperatureto reflux for one hour
6. 6
   Temperatureto cool
7. 7
   Otherwas partitioned between EtOAc and aqueous sodium hydrogen carbonate solution
8. 8
   OtherThe organic layer was separated
9. 9
   Washwashed with brine
10. 10
    Dryingdried (Na2SO4)
11. 11
    Otherthe volatiles removed by evaporation
12. 12
    OtherThe residue was purified by chromatography on silica eluting with DCM/7N methanolic ammonia (96:4)
13. 13
    OtherThe purified product was triturated with minimal hot EtOAc

Procedure

4-Amino-N-methyl-benzenesulphonamide (250 mg, 1.34 mmol) was dissolved in the minimum amount of MeOH and 1M ethereal hydrogen chloride (1.34 ml) added. The volatiles were removed by evaporation and cyanamide (68 mg, 1.62 mmol) was added followed by dimethylacetamide (0.5 ml) and the mixture heated at 100° C. for 45 minutes. The mixture was allowed to cool and 1-benzyl-5-(3-dimethylaminoprop-2-en-1-oyl)-2-methylimidazole (Method 50; 230 mg, 0.86 mmol) and sodium methoxide (150 mg, 2.78 mmol) were added and the mixture heated to reflux for one hour. The mixture allowed to cool and was partitioned between EtOAc and aqueous sodium hydrogen carbonate solution. The organic layer was separated, washed with brine, dried (Na2SO4) and the volatiles removed by evaporation. The residue was purified by chromatography on silica eluting with DCM/7N methanolic ammonia (96:4). The purified product was triturated with minimal hot EtOAc to give the title compound (260 mg, 70%) as a cream solid. NMR: 2.28 (s, 3H), 2.37 (d, 3H), 5.96 (s, 2H), 6.93 (d, 2H), 7.15-7.28 (m, 5H), 7.54 (d, 2H), 7.75-7.81 (m, 3H), 8.40 (d, 1H), 9.86 (s, 1H); m/z 435.

Source