Reacción #79779

Ecuación de reacción

2-bromo-2-methylpropanamide

hydrochloric acid

4-Amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidine

sodium hydroxide

2-Bromo-2-methylpropanamide

→

2-[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]-2-methylpropionamide

Disolventes

water

Water

1,3-dimethyl-3,4,5,6-tetrahydro-2-(1H)-pyrimidinone

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGthe mixture stirred for 15 minutes
2. 2
   workup.STIRRINGthe mixture was stirred vigorously for 18 hours at ambient temperature under a water-free atmosphere
3. 3
   workup.STIRRINGstirred for a further 24 hours
4. 4
   workup.WAITthe mixture left
5. 5
   FiltraciónThe solid was collected by filtration
6. 6
   Lavadowashed well with water
7. 7
   Otrodried under high vacuum at 50° C
8. 8
   OtroThe solid was purified by preparative HPLC (reverse phase)
9. 9
   OtroAppropriate fractions were collected
10. 10
    Extracciónextracted with dichloromethane
11. 11
    OtroEvaporation of the dichloromethane

Procedimiento

4-Amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidine (200 mg) was dissolved in 1,3-dimethyl-3,4,5,6-tetrahydro-2-(1H)-pyrimidinone (1.5 ml) with stirring and sodium hydroxide (0.158 g) was added at ambient temperature and the mixture stirred for 15 minutes. 2-Bromo-2-methylpropanamide (0.5 g) was added and the mixture was stirred vigorously for 18 hours at ambient temperature under a water-free atmosphere, then further 2-bromo-2-methylpropanamide (0.15 g) was added and stirred for a further 24 hours. Water (3 ml) was added to the reaction mixture together with dilute hydrochloric acid (5M) to adjust the pH to 0. The suspension was added to water (60 ml) and the mixture left to stand for 18 hours at ambient temperature. The solid was collected by filtration, washed well with water and dried under high vacuum at 50° C. The solid was purified by preparative HPLC (reverse phase). Appropriate fractions were collected and combined and extracted with dichloromethane. Evaporation of the dichloromethane gave 2-[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]-2-methylpropionamide, m.p. 227-228° C.

Fuente