Ammonia → 4-Chloro-6-(2-chloro-5-methylanilino)pyrimidine

HRID 987554Notes

Reaction equation

HRID 987554 reaction equation
C1S(=O)(=O)CCC1.Cl[C:9]1[CH:14]=[C:13]([Cl:15])[N:12]=[CH:11][N:10]=1.[Cl:16][C:17]1[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][C:18]=1[NH2:19].N>C(Cl)Cl>[Cl:15][C:13]1[CH:14]=[C:9]([NH:19][C:18]2[CH:20]=[C:21]([CH3:24])[CH:22]=[CH:23][C:17]=2[Cl:16])[N:10]=[CH:11][N:12]=1

Participants

6

Reactant 4

HCID 222AmmoniaHCID 31347SulfolaneHCID 667702-Chloro-5-methylanilineHCID 709434,6-Dichloropyrimidine

Product 1

HCID 180091384-Chloro-6-(2-chloro-5-methylanilino)pyrimidineYield 57.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
125 °C

Procedure

Tetramethylene sulphone (10 ml) was added to 4,6-dichloropyrimidine (25.0 g, 170 mmol) and heated to 125° C. 2-Chloro-5-methylaniline (11.90 g, 84 mmol) was added portion wise over 20 mins. The reaction mixture was heated at 125° C. for 2 hours. The reaction was allowed to cool to room temperature and DCM (200 ml) was added. The mixture was basified to pH 9-10 with methanolic ammonia and evaporated onto silica (15 g). The residue was purified by column chromatography eluting with EtOAc:isohexane (10:90) to give a white solid (12.25 g, 29%). NMR (300 MHz): 2.3 (s, 3H), 6.7 (s, 1H), 7.0 (d, 1H), 7.4 (d, 1H), 7.5 (s, 1H), 8.4 (s, 1H), 9.4 (s, 1H); m/z 254 (MH+).

Workup

  1. temperatureThe reaction mixture was heated at 125° C. for 2 hours
  2. temperatureto cool to room temperature
  3. customevaporated onto silica (15 g)
  4. customThe residue was purified by column chromatography
  5. washeluting with EtOAc:isohexane (10:90)

Sources & evidence

ORD record
ord-a791a57bdae54dddbdc61f321eca5112
Source dataset
uspto-grants-2003_10
Patent number
US06632820B1

Reaction notes

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