p-Toluenesulfonic acid → 5-(2,6-Dichlorophenyl)aminomethyl-4-amino-2-methylthiopyrimidine

HRID 1858197Notes

Reaction equation

HRID 1858197 reaction equation
[NH2:1][C:2]1[C:7]([CH:8]=S)=[CH:6][N:5]=[C:4](C)[N:3]=1.[Cl:11][C:12]1[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[C:13]=1[NH2:14].C1(C)C=C[C:23]([S:26](O)(=O)=O)=CC=1.[BH4-].[Na+]>C1(C)C(C)=CC=CC=1.O>[Cl:11][C:12]1[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[C:13]=1[NH:14][CH2:8][C:7]1[C:2]([NH2:1])=[N:3][C:4]([S:26][CH3:23])=[N:5][CH:6]=1

Participants

7

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 118462,6-DichloroanilineHCID 4311764Sodium borohydrideHCID 867560534-Amino-2-methylthiopyrimidine-5-carboxaldehyde

Product 1

HCID 221250215-(2,6-Dichlorophenyl)aminomethyl-4-amino-2-methylthiopyrimidineYield 143.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 7237O-XyleneSolvent

Procedure

A mixture of 10 g (59.2 mmol) of 4-amino-2-methylthiopyrimidine-5-carboxaldehyde, 9.7 g (59.9 mmol) of 2,6-dichloroaniline and 1 g (5.3 mmol) of 4-toluenesulfonic acid in 200 ml of xylene was heated at reflux with the azeotropic removal of water for 24 hours. The mixture was cooled and evaporated. 50 ml of acetic acid and 20 ml of toluene were added to the residue. The mixture was cooled in ice and treated portionwise over 30 minutes with 5 g (147 mmol) of sodium borohydride. After 1 hour the mixture was evaporated and the residue was stirred in a mixture of 100 ml of ethyl acetate and 100 ml of 2M aqueous sodium hydroxide for 1 hour. The phases were separated and the organic phase was dried over magnesium sulfate, filtered and evaporated. Crystallisation of the residue from aqueous ethanol gave 2.4 g (13%) of 5-(2,6-dichlorophenyl)aminomethyl-4-amino-2-methylthiopyrimidine as a white solid. The mother liquors were evaporated and flash chromatography of the residue on silica gel using diethyl ether/hexane (1:1) for the elution gave a further 2.1 g (11%) of 5-(2,6-dichlorophenyl)aminomethyl-4-amino-2-methylthiopyrimidine as a white solid.

Workup

  1. temperaturewas heated
  2. temperatureThe mixture was cooled
  3. customevaporated
  4. addition50 ml of acetic acid and 20 ml of toluene were added to the residue
  5. temperatureThe mixture was cooled in ice
  6. customAfter 1 hour the mixture was evaporated
  7. customThe phases were separated
  8. dry with materialthe organic phase was dried over magnesium sulfate
  9. filtrationfiltered
  10. customevaporated
  11. customCrystallisation of the residue from aqueous ethanol

Sources & evidence

ORD record
ord-a320720ee2f64e818677382f9ce7d9cd
Source dataset
uspto-grants-2000_11
Patent number
US06150373

Reaction notes

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