Hydrochloric Acid → 6-Chloro-5-(4-(1-hydroxy-2-methylpropan-2-yl)phenyl)-1H-indazole-3-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

A suspension of 2-(4-bromophenyl)-2-methylpropan-1-ol (168 mg, 0.73 mmol), 5,5,5′,5′-tetramethyl-2,2′-bi-1,3,2-dioxaborinane (275 mg, 0.81 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (30 mg, 0.037 mmol) and potassium acetate (216 mg, 2.20 mmol) in 1,4-dioxane (2 mL) was sealed in a pressure tube and heated to 130° C. for 1 hour. To the mixture was added 5-bromo-6-chloro-1H-indazole-3-carboxylic acid (100 mg, 0.36 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (14.7 mg, 0.018 mmol), 2N aqueous potassium carbonate solution (0.5 mL, 1.0 mmol) and EtOH (2 mL). The reaction mixture was sealed and heated to 130° C. for 1 hour. Water (3 mL) was added to the reaction mixture, followed by 1N HCl solution to adjust the pH to 2. The layers were separated and the aqueous layer was extracted with EtOAc (3×5 mL). The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by reverse phase HPLC (Column: Waters XBridge C18 19×100 mm, 5 μm; Mobile phase A: 0.03% NH4OH in water (v/v); Mobile phase B: 0.03% NH4OH in MeCN (v/v); 90.0% H2O/10.0% MeCN linear to 70.0% H2O/30.0% MeCN in 8.5 min, 70.0% H2O/30.0% MeCN linear to 0% H2O/100% MeCN in 0.5 min HOLD at 0% H2O/100% MeCN from 9.0 to 10.0 min. Flow: 25 mL/min) to afford the title compound (25.1 mg, 20% yield). MS (ES+) 345.1 (M+H)+. Retention time=1.59 minutes (Column: Waters XBridge dC18 4.6×50 mm, 5 μm; Mobile phase A: 0.03% NH4OH in water (v/v); Mobile phase B: 0.03% NH4OH in MeCN (v/v); Gradient: 95:5 A:B linear to 5:95 A:B in 4.0 min, hold at 5:95 A:B to 5.0 min. Flow: 2 mL/min).

Provenance & Evidence