Potassium Carbonate → 10-Chloro-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazole

To a solution of 4-[2-amino-4-chloro-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butan-1-ol (3.40 g, 10.8 mmol) in pyridine (50 mL) was added methanesulfonyl chloride (2.60 mL, 32.9 mmol) dropwise at 0° C. After stirring for 1 hr, aqueous sodium bicarbonate was added to the mixture, which was extracted with ethyl acetate. Organic layer was washed with 2N hydrochloric acid, water and brine, dried over sodium sulfate and concentrated in vacuo. The residue was dissolved in N,N-dimethylformamide (100 mL) and potassium carbonate (4.50 g, 32.9 mmol) was added. The mixture was stirred at 110° C. for 15 hr. After cooling, the mixture was diluted with ethyl acetate, washed with water and brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with a 30-100% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the title compound (1.51 g, 5.17 mmol, 47%) as a pale yellow solid.

1. extractionwas extracted with ethyl acetate
2. washOrganic layer was washed with 2N hydrochloric acid, water and brine
3. dry with materialdried over sodium sulfate
4. concentrationconcentrated in vacuo
5. dissolutionThe residue was dissolved in N,N-dimethylformamide (100 mL)
6. stirringThe mixture was stirred at 110° C. for 15 hr
7. temperatureAfter cooling
8. washwashed with water and brine
9. dry with materialdried over sodium sulfate
10. concentrationconcentrated in vacuo
11. customThe residue was purified by flash chromatography on silica gel eluting with a 30-100% ethyl acetate/n-hexane gradient mixture
12. concentrationThe filtrate was concentrated in vacuo

ORD-Eintrag

ord-ac45f6dff2534712a077fa17a2b3fcde

Quelldatensatz

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08785460B2