Water → 5-(4-Chloro-2-(difluoromethoxy)phenyl)-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-YL)naphthalene-2-sulfonamide

温度

100 °C

A microwave vial was charged with N-(2,4-dimethoxybenzyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (Intermediate E) (130 mg, 0.229 mmol), 1-bromo-4-chloro-2-(difluoromethoxy)benzene (Intermediate J) (118 mg, 0.458 mmol) and Pd(dppf)Cl2DCM (37.4 mg, 0.046 mmol). Dioxane (1145 μl) and t-butanol (1145 μl) were added to the reaction vial followed by sodium carbonate in water (362 μl, 0.687 mmol, 1.9 M). The vial was purged with nitrogen and sealed. The mixture was stirred and sonicated for 5 min. The resulting light red mixture was then heated in a microwave at 100° C. for 30 min LC/MS indicated complete conversion of boronic ester to the desired product. The reaction was cooled to rt and filtered through a fritted funnel with an aid of DCM (15 mL). The filtrate was acidified with 2N aqueous HCl to a pH of about 1. After stirring for 5 min at room temperature, the product was extracted with DCM (2×20 mL). The organic layers were combined, washed with brine, dried over MgSO4, filtered, and concentrated to afford a dark oil. MS (ESI): 639.8 [M+Na]+

1. customThe vial was purged with nitrogen
2. customsealed
3. customsonicated for 5 min
4. temperatureThe reaction was cooled to rt
5. filtrationfiltered through a fritted funnel with an aid of DCM (15 mL)
6. stirringAfter stirring for 5 min at room temperature
7. extractionthe product was extracted with DCM (2×20 mL)
8. washwashed with brine
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated
12. customto afford a dark oil

ORDレコード

ord-f7e4c819a6684a009b337e0b33c8ef31

出典データセット

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09012443B2