تفاعل #3513

معادلة التفاعل

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

المردود 27.9%

المذيبات

water

DMF

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGthe mixture was stirred for 18 hours
2. 2
   ترشيحthe insoluble material was collected by filtration
3. 3
   أخرىto form a solution
4. 4
   ترشيحthe suspension filtered through celite
5. 5
   غسيلwashing with water
6. 6
   ترشيحthe insoluble product was collected by filtration
7. 7
   غسيلwashed with water
8. 8
   أخرىA 180-mg sample of the product was further purified by reverse phase preparative HPLC on a C18 reverse phase column
9. 9
   غسيلeluting 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

الإجراء التجريبي

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.

المصدر