Reaction #86457

Reaction equation

N4-(4-(2-methoxyethoxy)-2-nitrophenyl)-N6-methylpyrimidine-4,6-diamine

2,6-dichloro-3,5-dimethoxyaniline

phosgene

toluene

→

title compound

Yield 32.0%

3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-(6-((4-(2-methoxyethoxy)-2-nitrophenyl)amino)pyrimidin-4-yl)-1-methylurea

Yield 32.0%

Solvents

—

Hexanes

EtOAc

dioxane

Conditions

Workup

1. 1
   Temperatureto cool to room temperature
2. 2
   OtherThe solvents were removed
3. 3
   workup.DISSOLUTIONthe residue was dissolved in toluene (10 mL)
4. 4
   OtherThe resultant reaction mixture
5. 5
   Temperaturewas then refluxed for 6 h
6. 6
   OtherAfter completion of the reaction
7. 7
   Temperaturewas cooled to room temperature
8. 8
   Concentrationconcentrated under vacuum
9. 9
   Otherto obtain a crude
10. 10
    Otherreaction mixture
11. 11
    OtherThe solid precipitated on addition of ethyl acetate to the crude
12. 12
    Otherreaction mixture
13. 13
    Filtrationwas filtered
14. 14
    Washwashed with ether and pentane

Procedure

To a stirred solution of 2,6-dichloro-3,5-dimethoxyaniline (500 g, 2.252 mmol) in dioxane (10 mL) was added 20% phosgene in toluene (4.4 mL, 9.0 mmol) under argon atmosphere at 0° C. The resulting mixture was stirred for 6 h at 90° C., and then allowed to cool to room temperature. The solvents were removed and the residue was dissolved in toluene (10 mL). To this, was added N4-(4-(2-methoxyethoxy)-2-nitrophenyl)-N6-methylpyrimidine-4,6-diamine (0.718 g, 8.358 mmol, 1.0 eq). The resultant reaction mixture was then refluxed for 6 h. After completion of the reaction by TLC (Hexanes:EtOAc, 7:3), reaction mixture was cooled to room temperature, concentrated under vacuum to obtain a crude reaction mixture. The solid precipitated on addition of ethyl acetate to the crude reaction mixture was filtered, washed with ether and pentane to afford the title compound (0.285, yield: 32%) as a white solid. MS (ESI): 567.0 [M+H]+.

Source