Chlorosulfonic acid → 4-(1,2-Dimethylimidazol-5-yl)-2-{4-[N-(1,3-dimethoxyprop-2-yl)sulphamoyl]anilino}pyrimidine

HRID 2375272Notes

Reaction equation

HRID 2375272 reaction equation
Cl[S:2]([OH:5])(=O)=[O:3].[NH:6]([C:13]1[N:18]=[C:17]([C:19]2[N:23]([CH3:24])[C:22]([CH3:25])=[N:21][CH:20]=2)[CH:16]=[CH:15][N:14]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[CH3:26][O:27][CH2:28][CH:29]([NH2:33])[CH2:30][O:31][CH3:32]>S(Cl)(Cl)=O.C(O)C.CN(C)CC>[CH3:24][N:23]1[C:19]([C:17]2[CH:16]=[CH:15][N:14]=[C:13]([NH:6][C:7]3[CH:12]=[CH:11][C:10]([S:2](=[O:5])(=[O:3])[NH:33][CH:29]([CH2:30][O:31][CH3:32])[CH2:28][O:27][CH3:26])=[CH:9][CH:8]=3)[N:18]=2)=[CH:20][N:21]=[C:22]1[CH3:25]

Participants

7

Reactant 3

HCID 24638Chlorosulfonic acidHCID 15141601,3-Dimethoxypropan-2-amineHCID 222734802-Anilino-4-(1,2-dimethylimidazol-5-yl)pyrimidine

Product 1

HCID 693130864-(1,2-Dimethylimidazol-5-yl)-2-{4-[N-(1,3-dimethoxyprop-2-yl)sulphamoyl]anilino}pyrimidine

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 11723DimethylethylamineSolventHCID 24386Thionyl ChlorideSolvent

Conditions

Temperature
5 °C

Procedure

Chlorosulphonic acid (230 μl, 3.31 mmol) was added to a solution of the 2-anilino-4-(1,2-dimethylimidazol-5-yl)pyrimidine (Method 34; 300 mg, 1.12 mmol) in thionyl chloride (6 ml) at 5° C. The mixture was stirred at 5° C. for 30 minutes, room temperature for 1 hour and heated at reflux for 1.5 hour. The mixture was allowed to cool to room temperature and a solution of excess 1,3-dimethoxy-2-aminopropane (Method 59) in ethanol (20 ml) and dimethylethylamine (0.5 ml) were added to the residue, and the mixture stirred at room temperature for 18 hours. The volatiles were removed by evaporation. The residue was triturated with water and the solid product collected by filtration and dried under vacuum at 60° C. The residue was purified by flash silica chromatography DCM:MeOH (95:5) to give the title compound. NMR: 2.40 (s, 3H), 3.10 (s, 6H), 3.20(d, 4H), 3.32-3.28 (m, 1H), 3.98 (s, 3H), 7.20 (d, 1H), 7.55 (d, 1H), 7.65 (s, 2H), 7.74 (d, 2H), 7.90 (d, 2H), 8.44 (d, 2H), 9.89 (s, 1H); m/z 447

Workup

  1. temperatureheated
  2. temperatureat reflux for 1.5 hour
  3. temperatureto cool to room temperature
  4. stirringthe mixture stirred at room temperature for 18 hours
  5. customThe volatiles were removed by evaporation
  6. customThe residue was triturated with water
  7. filtrationthe solid product collected by filtration
  8. customdried under vacuum at 60° C
  9. customThe residue was purified by flash silica chromatography DCM:MeOH (95:5)

Sources & evidence

ORD record
ord-3e69702123f7491984734750e526c53f
Source dataset
uspto-grants-2008_12
Patent number
US07465728B2

Reaction notes

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