Reacción #169334

Ecuación de reacción

Benzophenone imine

(5-bromopyridin-3-yl){7-[(1S)-1-methyl-2-(tetrahydro-2H-pyran-2-yloxy)ethyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}methanone

2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl

potassium phosphate tribasic

→

title compound

Rendimiento 70.0%

(5-Aminopyridin-3-yl){7-[(1S)-1-methyl-2-(tetrahydro-2H-pyran-2-yloxy)ethyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}methanone

Rendimiento 70.0%

Disolventes

DCM

1,2-dimethoxyethane

Condiciones de reacción

Tratamiento posterior

1. 1
   Filtraciónfiltered through Arbocel™
2. 2
   Lavadothe pad was washed with DCM (5 mL)
3. 3
   OtroThe filtrate was evaporated in vacuo
4. 4
   workup.DISSOLUTIONthe crude material was dissolved in THF (10 mL)
5. 5
   workup.ADDITIONAqueous citric acid (5 mL, 2M) was added
6. 6
   workup.STIRRINGthe mixture was stirred at room temperature for 16 hours
7. 7
   workup.ADDITIONWater (40 mL) was added
8. 8
   workup.ADDITIONsodium hydroxide was added
9. 9
   ExtracciónThe mixture was extracted with EtOAc (3×40 mL)
10. 10
    Secadothe combined organic extracts were dried over magnesium sulfate
11. 11
    Otroevaporated in vacuo
12. 12
    OtroThe residue was purified by column chromatography on silica gel (gradient of EtOAc:MeOH 100:0 to 80:20)

Procedimiento

Benzophenone imine (0.40 mL, 2.4 mmol) was added to (5-bromopyridin-3-yl){7-[(1S)-1-methyl-2-(tetrahydro-2H-pyran-2-yloxy)ethyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}methanone (891 mg, 2.0 mmol) (see Preparation 27), tris(dibenzylideneacetone)dipalladium (55 mg, 0.06 mmol), 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (68 mg, 0.16 mmol) and freshly ground potassium phosphate tribasic (1.06 g, 5.0 mmol) in 1,2-dimethoxyethane (4 mL). The mixture was stirred at 50° C. for 17 hours. The reaction mixture diluted with DCM (10 mL), filtered through Arbocel™ and the pad was washed with DCM (5 mL). The filtrate was evaporated in vacuo and the crude material was dissolved in THF (10 mL). Aqueous citric acid (5 mL, 2M) was added and the mixture was stirred at room temperature for 16 hours. Water (40 mL) was added then sodium hydroxide was added to basify the mixture. The mixture was extracted with EtOAc (3×40 mL) and the combined organic extracts were dried over magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica gel (gradient of EtOAc:MeOH 100:0 to 80:20) to afford the title compound as a white solid in 70% yield, 506 mg.

Fuente