Sodium Methoxide → 2,4-Pyrimidinediamine, 5-(3-((4'-chloro(1,1'-biphenyl)-4-yl)oxy)propoxy)-6-methyl-, monohydrochloride

HRID 1758479Notes

Reaction equation

HRID 1758479 reaction equation
S(O)(O)(=O)=O.[NH2:6][C:7]1[N:12]=[C:11]([NH2:13])[C:10]([OH:14])=[C:9]([CH3:15])[N:8]=1.C[O-].[Na+].[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[CH:36]=[CH:35][C:29]([O:30][CH2:31][CH2:32][CH2:33]Br)=[CH:28][CH:27]=2)=[CH:22][CH:21]=1>O1CCCC1>[ClH:19].[NH2:6][C:7]1[N:12]=[C:11]([NH2:13])[C:10]([O:14][CH2:33][CH2:32][CH2:31][O:30][C:29]2[CH:35]=[CH:36][C:26]([C:23]3[CH:22]=[CH:21][C:20]([Cl:19])=[CH:25][CH:24]=3)=[CH:27][CH:28]=2)=[C:9]([CH3:15])[N:8]=1

Participants

5

Reactant 3

HCID 10942334Sodium MethoxideHCID 12803794HCID 12803794, compoundHCID 20509381HCID 20509381, compound

Product 1

HCID 1986042,4-Pyrimidinediamine, 5-(3-((4'-chloro(1,1'-biphenyl)-4-yl)oxy)propoxy)-6-methyl-, monohydrochlorideYield 146.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

2,4-Diamino-5-hydroxy-6-methylpyrimidine dihydrogen sulphate (137.5 g) was added to a stirred solution of sodium methoxide [prepared by dissolving sodium (39.8 g) in anhydrous methanol (2350 ml)]. The stirred mixture was heated at reflux for 30 minutes and then for a further 150 minutes during the gradual addition of a solution of 3-[4-(4-chlorophenyl)-phenoxy]propyl bromide (188 g) in anhydrous tetrahydrofuran (940 ml) and then the mixture was stirred and heated at reflux for a further 18 hours. Part of the solvent (approximately 2400 ml) was removed by distillation at atmospheric pressure and the remaining mixture was diluted with water (3000 ml). The resulting suspension was cooled to 40° C., and the solid was filtered off, washed well with water and dried at 85° C. The solid was then dissolved in hot dimethylformamide (1000 ml) and the resulting solution was filtered through diatomaceous earth and treated, successively, with concentrated hydrochloric acid (50 ml) and acetone (2000 ml). The resulting suspension was cooled to 10° C. and filtered, and the solid was washed well with acetone to give 2,4-diamino-5-[3-{4-(4-chlorophenyl)phenoxy}propoxy]-6-methylpyrimidine monohydrochloride (178 g), m.p. 263°-265° C. (with slight decomposition).

Workup

  1. temperatureThe stirred mixture was heated
  2. temperatureat reflux for 30 minutes
  3. temperatureheated
  4. temperatureat reflux for a further 18 hours
  5. customPart of the solvent (approximately 2400 ml) was removed by distillation at atmospheric pressure
  6. additionthe remaining mixture was diluted with water (3000 ml)
  7. filtrationthe solid was filtered off
  8. washwashed well with water
  9. customdried at 85° C
  10. dissolutionThe solid was then dissolved in hot dimethylformamide (1000 ml)
  11. filtrationthe resulting solution was filtered through diatomaceous earth
  12. additiontreated
  13. temperatureThe resulting suspension was cooled to 10° C.
  14. filtrationfiltered
  15. washthe solid was washed well with acetone

Sources & evidence

ORD record
ord-f729d6b96cfc4e8db3e006f6b7584db7
Source dataset
uspto-grants-1983_02
Patent number
US04374136

Reaction notes

Loading…