Reaktion #3513

Reaktionsgleichung

charcoal

t-butyl isocyanate

7-amino-6-(2,6-dichlorophenyl)-2-(3-diethylamino-propylamino)-pyrido[2,3-d]pyrimidine

sodium hydride

→

1-tert-butyl-3-[6-(2,6-dichlorophenyl)-2-(3-diethylamino-propylamino)-pyrido[2,3-d]pyrimidin-7-yl]-urea

Ausbeute 27.9%

Lösungsmittel

water

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGthe mixture was stirred for 18 hours
2. 2
   Filtrationthe insoluble material was collected by filtration
3. 3
   Sonstigeto form a solution
4. 4
   Filtrationthe suspension filtered through celite
5. 5
   Waschenwashing with water
6. 6
   Filtrationthe insoluble product was collected by filtration
7. 7
   Waschenwashed with water
8. 8
   SonstigeA 180-mg sample of the product was further purified by reverse phase preparative HPLC on a C18 reverse phase column
9. 9
   Wascheneluting with a solvent gradient
10. 10
    workup.WAITstarting from 86% of 0.1% trifluoroacetic acid in water/14% acetonitrile to 14% of 0.1% trifluoroacetic acid in water/86% acetonitrile over a 22-minute

Vorschrift

To a solution of 7-amino-6-(2,6-dichlorophenyl)-2-(3-diethylamino-propylamino)-pyrido[2,3-d]pyrimidine (0.48 g) from Example 20 in DMF (5 mL) was added 60% sodium hydride suspension (46 mg), and the mixture was stirred for 1 hour at room temperature. To the reaction mixture was added t-butyl isocyanate (0.113 g), and the mixture was stirred for 18 hours. The reaction mixture was diluted with water and the insoluble material was collected by filtration. The solid was suspended in water (20 mL) and acidified with 1.0N HCl to form a solution. Activated charcoal was added to the solution, and the suspension filtered through celite, washing with water. The filtrate was made basic with 1.0N NaOH, and the insoluble product was collected by filtration and washed with water. A 180-mg sample of the product was further purified by reverse phase preparative HPLC on a C18 reverse phase column, eluting with a solvent gradient starting from 86% of 0.1% trifluoroacetic acid in water/14% acetonitrile to 14% of 0.1% trifluoroacetic acid in water/86% acetonitrile over a 22-minute time period to afford 165 mg of 1-tert-butyl-3-[6-(2,6-dichlorophenyl)-2-(3-diethylamino-propylamino)-pyrido[2,3-d]pyrimidin-7-yl]-urea, mp dec >80° C.

Quelle