Triethylamine → 2-(((3-methyl-4-(2-(2-propyl-1,3-dioxolan-2-yl)ethoxy)pyridin-2-yl)methyl)thio)-1H-benzimidazole

The (3-methyl-4-(2-(2-propyl-1,3-dioxolan-2-yl)ethoxy)pyridin-2-yl)methanol (450 mg, 1.6 mmol) obtained in the step (3e) was mixed with tetrahydrofuran (10 ml). The mixture was cooled on ice in a nitrogen atmosphere. To this, triethylamine (0.446 ml, 3.2 mmol), and methanesulfonyl chloride (0.186 ml, 2.4 mmol) were added and stirred for 50 minutes under ice-cooling. To the reaction mixture, 2-mercaptobenzimidazole (240 mg, 1.6 mmol) was added and stirred at room temperature overnight. To the reaction mixture, an aqueous solution of sodium hydrogen carbonate was added and extracted with ethyl acetate. The organic layer was washed with a saturated saline solution, dried over magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure. The residue was dissolved in ethyl acetate. After silica gel was added to the solution, the solution was concentrated. The dried residue was subjected to silica gel column chromatography (elution solvent: n-heptane/ethyl acetate=1/1→0/1) to obtain the title compound (528 mg, 79.8%) as a colorless viscous oil.

1. temperatureThe mixture was cooled on ice in a nitrogen atmosphere
2. temperaturecooling
3. stirringstirred at room temperature overnight
4. extractionextracted with ethyl acetate
5. washThe organic layer was washed with a saturated saline solution
6. dry with materialdried over magnesium sulfate
7. filtrationfiltered
8. concentrationThe filtrate was concentrated under reduced pressure
9. dissolutionThe residue was dissolved in ethyl acetate
10. additionAfter silica gel was added to the solution
11. concentrationthe solution was concentrated
12. washThe dried residue was subjected to silica gel column chromatography (elution solvent: n-heptane/ethyl acetate=1/1→0/1)

ORDレコード

ord-7afa0bd1811845fc9489431a2d1a8149

出典データセット

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08124780B2