Potassium Carbonate → Methyl 9-chloro-1-(3,5-dichloropyridin-2-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylate

Methanesulfonyl chloride (1.8 mL, 23.1 mmol) was added to a stirred solution of methyl 4-chloro-2-[(3,5-dichloropyridin-2-yl)amino]-1-(3-hydroxypropyl)-1H-benzimidazole-7-carboxylate (Reference example 123, 3.32 g, 7.73 mmol) and triethylamine (4.3 mL) in tetrahydrofuran (100 mL) at 0° C. The mixture was stirred at room temperature for 5 hr. The mixture was diluted with aqueous sodium hydrogen carbonate, and the precipitate was collected by filtration. A mixture of the resulting mesylate and potassium carbonate (4.27 g, 30.9 mmol) in N,N-dimethylformamide (40 mL) was stirred at 80° C. for 2 hr. The mixture was diluted with water, and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with a 20-50% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the solid, which was washed with diisopropyl ether to give the title compound as a colorless powder (2.37 g, 5.76 mmol, 75% in 2 steps).

1. filtrationthe precipitate was collected by filtration
2. stirringwas stirred at 80° C. for 2 hr
3. extractionextracted with ethyl acetate
4. washThe combined organic layer was washed with brine
5. dry with materialdried over anhydrous magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was purified by flash column chromatography on silica gel eluting with a 20-50% ethyl acetate/n-hexane gradient mixture
9. concentrationThe filtrate was concentrated in vacuo
10. customto give the solid, which
11. washwas washed with diisopropyl ether

ORD-Eintrag

ord-5f1ef5b35a2b438288265112817ccb87

Quelldatensatz

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08785460B2