Acetic Anhydride → 1-(4-(5-(3-(2-Methylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)piperidin-1-yl)ethanone

N-(3-(2-methylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-yl)-3-(piperidin-4-yl)-1,2,4-thiadiazol-5-amine (29.52 g, 61.81 mmol) and triethylamine (21.54 ml, 154.5 mmol) were dissolved in THF (300 mL). Acetic anhydride (6.310 g, 61.81 mmol) was added and the reaction was stirred for 90 minutes. Saturated sodium bicarbonate (200 mL) and water (400 mL) were added and the reaction mixture was extracted with dichloromethane and 10% methanol in dichloromethane. The combined organic layers were dried over sodium sulfate, filtered and concentrated. The residue was dissolved in MeOH (˜75 mL) and let stand. The resultant solids were filtered and washed with cold methanol to give a first crop (22.3 g). The filtrate was concentrated and solids were redissolved in methanol (30 mL) and allowed to stand. The precipitated solids were filtered and washed to afford a second crop (4.3 g). The 2 crops were combined to afford 1-(4-(5-(3-(2-methylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)piperidin-1-yl)ethanone (26.7 g, 51.38 mmol, 83.13% yield).

1. extractionthe reaction mixture was extracted with dichloromethane and 10% methanol in dichloromethane
2. dry with materialThe combined organic layers were dried over sodium sulfate
3. filtrationfiltered
4. concentrationconcentrated
5. dissolutionThe residue was dissolved in MeOH (˜75 mL)
6. filtrationThe resultant solids were filtered
7. washwashed with cold methanol
8. customto give a first crop (22.3 g)
9. concentrationThe filtrate was concentrated
10. dissolutionsolids were redissolved in methanol (30 mL)
11. filtrationThe precipitated solids were filtered
12. washwashed
13. customto afford a second crop (4.3 g)

ORDレコード

ord-c626aaf51dec488f84948ce40658c974

出典データセット

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08362037B2