p-Toluenesulfonic acid → HCID 18425436, compound

HRID 1280552Notes

Reaction equation

HRID 1280552 reaction equation
[CH3:1][NH:2][C:3]1[C:8]([CH:9]=S)=[CH:7][N:6]=[C:5](C)[N:4]=1.[Cl:12][C:13]1[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[C:14]=1[NH2:15].C1(C)C=C[C:24]([S:27](O)(=O)=O)=CC=1.[BH4-].[Na+]>C1(C)C=CC=CC=1.O>[Cl:12][C:13]1[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[C:14]=1[NH:15][CH2:9][C:8]1[C:3]([NH:2][CH3:1])=[N:4][C:5]([S:27][CH3:24])=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 118462,6-DichloroanilineHCID 4311764Sodium borohydrideHCID 865928692-Methyl-4-(methylamino)pyrimidine-5-carbothialdehyde

Product 1

HCID 18425436HCID 18425436, compoundYield 298%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of 4-methylamino-2-methylthiopyrimidine-5-carboxaldehyde (6 g, 32.8 mmol), 2,6-dichloroaniline (5.5 g, 33.9 mmol) and 4-toluene-sulfonic acid (1 g, 5.3 mmol) in 70 mL of toluene was heated under reflux with azeotropic removal of water for 17 hours. The mixture was concentrated to a volume of about 10 mL under reduced pressure and then treated with 120 mL of ethanol. The suspension obtained was heated to 75° C. and treated over a period of 15 minutes with 6.2 g (160 mmol) of sodium borohydride pellets. The mixture was stirred for a further 15 minutes and cooled to room temperature. The solvent was evaporated under reduced pressure and the residue was stirred in a mixture of 200 mL of 2M sodium hydroxide solution and 200 mL of ethyl acetate for 1 hour. The phases were separated and the organic phase was dried over magnesium sulfate and filtered. Evaporation of the filtrate under reduced pressure and flash chromatography of the residue using 3:7 diethyl ether/hexane for the elution gave 5.2 g (48%) of 5-(2,6-dichlorophenyl)aminomethyl-4-methylamino-2-methylthio-pyrimidine as a white solid.

Workup

  1. temperaturewas heated
  2. concentrationThe mixture was concentrated to a volume of about 10 mL under reduced pressure
  3. additiontreated with 120 mL of ethanol
  4. customThe suspension obtained
  5. temperaturecooled to room temperature
  6. customThe solvent was evaporated under reduced pressure
  7. stirringthe residue was stirred in a mixture of 200 mL of 2M sodium hydroxide solution and 200 mL of ethyl acetate for 1 hour
  8. customThe phases were separated
  9. dry with materialthe organic phase was dried over magnesium sulfate
  10. filtrationfiltered
  11. customEvaporation of the filtrate under reduced pressure and flash chromatography of the residue
  12. washfor the elution

Sources & evidence

ORD record
ord-af3f1183d80e4ac0801c178266ad1aaa
Source dataset
uspto-grants-2002_09
Patent number
US06451804B1

Reaction notes

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