2,6-Dichloroaniline → HCID 22125011, compound

HRID 1858240Notes

Reaction equation

HRID 1858240 reaction equation
[CH:1]([C:3]1[C:4]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([CH2:18][CH2:19][OH:20])[CH:13]=2)=[N:5][C:6]([S:9][CH3:10])=[N:7][CH:8]=1)=O.[Cl:21][C:22]1[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[C:23]=1[NH2:24].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1(C)C=CC=CC=1.O1CCCC1.O>[Cl:21][C:22]1[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[C:23]=1[NH:24][CH2:1][C:3]1[C:4]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([CH2:18][CH2:19][OH:20])[CH:13]=2)=[N:5][C:6]([S:9][CH3:10])=[N:7][CH:8]=1

Participants

8

Reactant 4

HCID 118462,6-DichloroanilineHCID 521998p-Toluenesulfonic acid monohydrateHCID 21226445Aluminium lithium hydrideHCID 22125006HCID 22125006, compound

Product 1

HCID 22125011HCID 22125011, compoundYield 17%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4 g (13.8 mmol) of 5-formyl-4-[3-(2-hydroxyethyl)phenyl]amino-2-methylthiopyrimidine in 80 ml of toluene was treated with 2.4 g (15 mmol) of 2,6-dichloroaniline and 0.25 g (1.3 mmol) of 4-toluenesulfonic acid monohydrate and the mixture was heated under reflux with azeotropic removal of water for 18 hours and then cooled. The mixture was evaporated and the residue was dissolved in 40 ml of tetrahydrofuran and added dropwise to a solution of 0.6 g (16 mmol) of lithium aluminium hydride in 40 ml of tetrahydrofuran. After 1 hour the reaction was quenched by the cautious dropwise addition of 0.6 ml of water, 0.6 ml of 2M aqueous sodium hydroxide and 1.8 ml of water. The resulting suspension was filtered through a filter aid and the filtrate was evaporated. The residue was subjected to column chromatography on silica using dichloromethane/methanol for the elution in a gradient from a ratio of 50:1 to a ratio of 10:1. Product-containing fractions from the first product to be eluted from the column were combined and evaporated to give 1 g (17%) of 5-(2,6-dichloroanilino)methyl-4-[3-(2-hydroxyethyl)phenyl]amino-2-methylthiopyrimidine as a white solid. Mass spectrum (ESI) MH+ =435. Product-containing fractions from the second product to be eluted from the column were combined and evaporated to give 1.8 g (45%) of 5-hydroxymethyl-4-[3-(2-hydroxyethyl)phenyl]amino-2-methylthiopyrimidine as a white solid. [Mass spectrum (ESI) MH+ =292].

Workup

  1. temperaturethe mixture was heated
  2. temperaturecooled
  3. customThe mixture was evaporated
  4. dissolutionthe residue was dissolved in 40 ml of tetrahydrofuran
  5. customAfter 1 hour the reaction was quenched by the cautious dropwise addition of 0.6 ml of water, 0.6 ml of 2M aqueous sodium hydroxide and 1.8 ml of water
  6. filtrationThe resulting suspension was filtered through a filter aid
  7. customthe filtrate was evaporated
  8. washfor the elution in a gradient from a ratio of 50:1 to a ratio of 10:1
  9. washProduct-containing fractions from the first product to be eluted from the column
  10. customevaporated

Sources & evidence

ORD record
ord-47f84b33205b43d5ae8c812058c30be8
Source dataset
uspto-grants-2000_11
Patent number
US06150373

Reaction notes

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