Reacción #41702

Ecuación de reacción

tin(II) chloride dihydrate

sodium bicarbonate

4-methanesulfonyl-phenol

cesium carbonate

N-(4-((2R,5S)-1-acetyl-5-methylpyrrolidin-2-yl)-5-fluoro-2-nitrophenyl)pyrazine-2-carboxamide

→

6-((2R,5S)-1-acetyl-5-methylpyrrolidin-2-yl)-5-(4-methanesulfonyl-phenoxy)-2-pyrazin-2-yl-1H-benzimidazole

Disolventes

Ethyl acetate

N-methylpyrrolidinone

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrothe reaction liquid
2. 2
   Otrothe reaction liquid
3. 3
   workup.STIRRINGwas stirred at 90° C. for 1 h our
4. 4
   workup.WAITat 100° C. for 2 hours
5. 5
   Otrothe resulting deposit was removed through filtration
6. 6
   Extracciónextracted with ethyl acetate
7. 7
   Lavadothe organic layer was washed with water and saturated saline
8. 8
   Secadodried with anhydrous magnesium sulfate
9. 9
   OtroThe solvent was evaporated away under reduced pressure
10. 10
    Otropurified
11. 11
    Otrothrough partitioning thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1)
12. 12
    Otroto obtain the entitled compound as a pale yellow oily substance

Procedimiento

9.2 mg of 4-methanesulfonyl-phenol and 26.2 mg of cesium carbonate were added to an N-methylpyrrolidinone (1 ml) solution of 10.4 mg of N-(4-((2R,5S)-1-acetyl-5-methylpyrrolidin-2-yl)-5-fluoro-2-nitrophenyl)pyrazine-2-carboxamide, and the reaction liquid was stirred at 90° C. for 1 hour. 60 mg of tin(II) chloride dihydrate was added to it, and the reaction liquid was stirred at 90° C. for 1 h our and at 100° C. for 2 hours. Ethyl acetate and aqueous saturated sodium bicarbonate were added to the reaction liquid, the resulting deposit was removed through filtration, extracted with ethyl acetate, and the organic layer was washed with water and saturated saline, and dried with anhydrous magnesium sulfate. The solvent was evaporated away under reduced pressure, and purified through partitioning thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1) to obtain the entitled compound as a pale yellow oily substance.

Fuente