Potassium Carbonate → HCID 89862967, compound

Temperature

90 °C

To a degassed solution of Intermediate 11A (3.00 g, 9.99 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (4.410 g, 14.99 mmol) and potassium carbonate (4.14 g, 30.0 mmol) in dioxane (20 mL)/water (8 mL) was added Tetrakis (0.577 g, 0.500 mmol). The vial was purged with argon, sealed and stirred at 90° C. for 16 h. Another 20% of tetrakis and boronic ester were added and the reaction mixture was degassed and heated at 90° C. for 24 h. The reaction was cooled down to rt and NaOH (14.99 mL, 14.99 mmol) was added and the reaction was stirred at 50° C. for 5 h. The mixture was partitioned between EtOAc and water. The organic layer was separated. The aqueous phase was extracted with EtOAc, and the combined organic layers were dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography over 120 g of silica gel (15 min gradient, with 0-100% ethyl acetate in hexanes) to afford Intermediate 11B (2.14 g, 7.45 mmol, 74.5% yield) as a white solid. LCMS=1.86 min [M+1]=288.2 (Method B).

1. customThe vial was purged with argon
2. customsealed
3. additionAnother 20% of tetrakis and boronic ester were added
4. customthe reaction mixture was degassed
5. temperatureheated at 90° C. for 24 h
6. temperatureThe reaction was cooled down to rt
7. stirringthe reaction was stirred at 50° C. for 5 h
8. customThe mixture was partitioned between EtOAc and water
9. customThe organic layer was separated
10. extractionThe aqueous phase was extracted with EtOAc
11. dry with materialthe combined organic layers were dried over MgSO4
12. concentrationconcentrated in vacuo
13. customThe crude material was purified by flash chromatography over 120 g of silica gel (15 min gradient, with 0-100% ethyl acetate in hexanes)

ORD record

ord-a85c802e14af48c6b30dc99c66f368e1

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09394260B2