p-Toluenesulfonic acid → 5-(2-Methylphenyl)aminomethyl-4-methylamino-2-methylthiopyrimidine

HRID 1858227Notes

Reaction equation

HRID 1858227 reaction equation
[CH3:1][NH:2][C:3]1[C:8]([CH:9]=S)=[CH:7][N:6]=[C:5](C)[N:4]=1.[NH2:12][C:13]1[C:14]([CH3:19])=[CH:15][CH:16]=[CH:17][CH:18]=1.C1(C)C=C[C:23]([S:26](O)(=O)=O)=CC=1.[BH4-].[Na+]>C1(C)C=CC=CC=1.O>[CH3:19][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[NH:12][CH2:9][C:8]1[C:3]([NH:2][CH3:1])=[N:4][C:5]([S:26][CH3:23])=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 7242O-ToluidineHCID 4311764Sodium borohydride2×HCID 865928692-Methyl-4-(methylamino)pyrimidine-5-carbothialdehyde

Product 1

HCID 221251655-(2-Methylphenyl)aminomethyl-4-methylamino-2-methylthiopyrimidineYield 230.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 300 mg (1.6 mmol) of 4-methylamino-2-methylthiopyrimidine-5-carboxaldehyde, 0.20 ml (1.8 mmol) of o-toluidine and 59 mg (0.3 mmol) of 4-toluenesulfonic acid in 50 ml of toluene was heated at reflux with azeotropic removal of water for 18 hours. The mixture was cooled and evaporated. The residue was dissolved in 40 ml of ethanol and heated to 70° C. 300 mg (8 mmol) of sodium borohydride were added cautiously and the mixture was heated at 70° C. for 2 hours. A further 300 mg (0.8 mmol) of sodium borohydride were added cautiously and the heating was continued for a further hour. The mixture was cooled and then evaporated. The residue was partitioned between 50 ml of 2M aqueous sodium hydroxide solution and 50 ml of ethyl acetate. The organic phase was dried over magnesium sulfate, filtered and evaporated. The residue was subjected to column chromatography on silica gel using diethyl ether/hexane (1:1) for the elution. Product-containing fractions were combined and evaporated to give 190 mg (43%) of 5-(2-methylphenyl)aminomethyl-4-methylamino-2-methylthiopyrimidine as a white solid. [Mass spectrum (ESI) MH+ =275].

Workup

  1. temperaturewas heated
  2. temperatureThe mixture was cooled
  3. customevaporated
  4. dissolutionThe residue was dissolved in 40 ml of ethanol
  5. temperaturethe mixture was heated at 70° C. for 2 hours
  6. waitthe heating was continued for a further hour
  7. temperatureThe mixture was cooled
  8. customevaporated
  9. customThe residue was partitioned between 50 ml of 2M aqueous sodium hydroxide solution and 50 ml of ethyl acetate
  10. dry with materialThe organic phase was dried over magnesium sulfate
  11. filtrationfiltered
  12. customevaporated
  13. washfor the elution
  14. customevaporated

Sources & evidence

ORD record
ord-19505971fa554b1ab22d90b2fb3cdf91
Source dataset
uspto-grants-2000_11
Patent number
US06150373

Reaction notes

Loading…