Hydrochloric Acid → 2,5-Dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-4-yloxy]-N-[1,3,4]thiadiazol-2-yl-benzamide

To a solution of 0.10 g (0.16 mmol) 5-{2,5-dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-4-yloxy]-benzoylamino}-[1,3,4]thiadiazole-2-carboxylic acid ethyl ester (Example 47) in 1 mL dioxane were added 1 mL water and 0.008 g (0.19 mmol) lithiumhydroxide monohydrate. The resulting suspension was stirred for 2 hours at room temperature and then at 80° C. for 5.5 hours. Another 0.001 g (0.024 mmol) lithiumhydroxide monohydrate was added and the reaction mixture was heated for another 1.5 hours at 80° C. After stirring at room temperature for 64 hours the reaction mixture was poured on 1M aqueous hydrochloric acid and ethyl acetate and the layers were separated. The aqueous layer was extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and evaporated. The residue was dissolved in N,N-dimethylformamide, filtered over a syringe microfilter and purified by preparative HPLC (Phenomenex Gemini column) with a gradient of acetonitrile:water (containing 0.05% formic acid) (10:90 to 98:2) to give 0.030 g (33%) of the product as a light yellow solid. MS (ESI): m/z=567.08 [M+H]+.

1. waitat 80° C. for 5.5 hours
2. temperaturethe reaction mixture was heated for another 1.5 hours at 80° C
3. stirringAfter stirring at room temperature for 64 hours the reaction mixture
4. customthe layers were separated
5. extractionThe aqueous layer was extracted three times with ethyl acetate
6. washThe combined organic layers were washed with brine
7. dry with materialdried over magnesium sulfate
8. filtrationfiltered
9. customevaporated
10. dissolutionThe residue was dissolved in N,N-dimethylformamide
11. filtrationfiltered over a syringe microfilter
12. custompurified by preparative HPLC (Phenomenex Gemini column) with a gradient of acetonitrile

ORDレコード

ord-f2f068e1318c4b1faaf3cb7a0d19d8b9

出典データセット

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08420647B2