Reaction #1702113

Reaction equation

NaHCO3

2,5-dichloro-N-(3-methoxybenzyl)pyrimidin-4-amine

2,5-Dichloro-N-(3-methoxybenzyl)pyrimidin-4-amine

2-(3-aminophenyl)ethanol

p-toluenesulfonic acid monohydrate

→

desired product

Yield 74.0%

2-[3-({5-Chloro-4-[(3-methoxybenzyl)amino]pyrimidin-2-yl}amino)phenyl]ethanol

Yield 74.0%

Solvents

1,4-dioxane

Conditions

Workup

1. 1
   OtherThe organic solvent was removed under vacuum
2. 2
   workup.ADDITIONfollowed by the addition of water and EtOAc
3. 3
   ExtractionThe aqueous layer was extracted with EtOAc twice
4. 4
   Dryingdried over Na2SO4
5. 5
   Concentrationconcentrated under vacuum
6. 6
   OtherThe crude was purified by silica gel column chromatography

Procedure

Into a reaction flask were added 2,5-dichloro-N-(3-methoxybenzyl)pyrimidin-4-amine (0.33 g, 1.2 mmol) (prepared according to Example 1, step A), 1,4-dioxane (20 mL), 2-(3-aminophenyl)ethanol (0.22 g, 1.6 mmol), and p-toluenesulfonic acid monohydrate (0.080 g, 0.42 mmol). The mixture was heated at 105° C. for 3 hours and then an aqueous solution of NaHCO3 (saturated) was added. The organic solvent was removed under vacuum followed by the addition of water and EtOAc. The aqueous layer was extracted with EtOAc twice. The organic layers were combined, dried over Na2SO4, and concentrated under vacuum. The crude was purified by silica gel column chromatography to provide the desired product as a white solid (0.33 g, 74% yield). LCMS for C20H22ClN4O2 (M+H)+: m/z=385.1.

Source