Reaction #3579

Reaction equation

HCl

potassium hexamethyldisilazane

6-(2,6-dichlorophenyl)-N2 -(4-diethylamino-butyl)-pyrido[2,3-d]pyrimidine-2,7-diamine

6-(2,6-Dichlorophenyl)-N2 -(4-diethylamino-butyl)-pyrido[2,3-d]pyrimidine-2,7-diamine

ethyl isocyanate

→

title compound

1-[6-(2,6-Dichlorophenyl)-2-(4-diethylamino-butyl-amino)-pyrido[2,3-d]pyrimidin-7-yl]-3-ethyl-urea

Solvents

THF

Conditions

Workup

1. 1
   workup.STIRRINGthe reaction mixture was stirred for an additional 18 hours at ambient temperature
2. 2
   OtherThe product was isolated
3. 3
   Filtrationfiltering the resulting solution
4. 4
   Extractionthe aqueous layer was extracted twice with ethyl acetate
5. 5
   DryingThe combined organic extracts were dried (MgSO4)
6. 6
   Filtrationfiltered
7. 7
   Concentrationthe filtrate concentrated under vacuum
8. 8
   OtherThe product was purified by radial chromatography
9. 9
   Washeluting with a solvent mixture of 90:10:1 EtOAC

Procedure

To a cooled (5° C.) solution of 6-(2,6-dichlorophenyl)-N2 -(4-diethylamino-butyl)-pyrido[2,3-d]pyrimidine-2,7-diamine (0.61 g) from Example 53 in THF (6 mL) was added potassium hexamethyldisilazane (0.308 g) in portions. The reaction mixture was allowed to warm to ambient temperature and stirred for 30 minutes. Then ethyl isocyanate was added, and the reaction mixture was stirred for an additional 18 hours at ambient temperature. The product was isolated by pouring the reaction mixture into approximately 200 mL of 0.25N aqueous HCl and filtering the resulting solution. The filtrate was made basic with 50% aqueous sodium hydroxide, and the aqueous layer was extracted twice with ethyl acetate. The combined organic extracts were dried (MgSO4), filtered, and the filtrate concentrated under vacuum. The product was purified by radial chromatography eluting with a solvent mixture of 90:10:1 EtOAC:MeOH:TEA to afford the title compound.

Source