7-Bromo-4-chloro-1-(2,2,2-trifluoroethyl)-N,N-bis(trimethylsilyl)-1H-indazol-3-amine (29.0 g, 1.0 eq, 61.3 mmol) was dissolved in anhydrous toluene (203 mL, 7 V) and transferred to an oven-dried flask under N₂. The flask was equipped with a magnetic stirrer and a J-Kem temperature probe to measure the internal temperature. The assembly was cooled to 0 °C, and isopropylmagnesium chloride–lithium chloride complex in THF (1.3 M, 13.36 g, 71 mL, 1.5 eq, 92 mmol) was added slowly while maintaining the internal temperature below 10 °C. The addition was completed in 15 min, and the reaction mixture was stirred at the same temperature for an additional 1.5 h.
After completion of the magnesium–halogen exchange, as monitored by crude ¹H NMR and TLC, 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (14 g, 15.3 mL, 1.2 eq, 73.6 mmol) was added slowly while maintaining the internal temperature below 5 °C. After the addition was complete, the resulting mixture was stirred at 0 °C for 3 h, then warmed to 25 °C and stirred for an additional 12 h.
Upon completion, the reaction mixture was quenched with water (116 mL, 4 V) at 25 °C and stirred for 5 min. The aqueous phase was extracted with ethyl acetate (230 mL, 8 V) and filtered through Celite. The organic layer was separated, washed with brine, dried, and concentrated.
The resulting residue was dissolved in THF/CH₃CN (10:1, 230 mL, 8 V), and HCl (1 M, 184 mL, 3 eq, 184 mmol) was added slowly while maintaining the temperature below 35 °C. The mixture was stirred for an additional 2 h. After completion of the deprotection, the aqueous THF/CH₃CN medium was extracted with ethyl acetate (290 mL, 10 V), and the solvent was evaporated.
Heptanes/iPrOAc (9:1, 290 mL, 10 V, based on the mass of the crude material isolated after deprotection) was added, and the mixture was heated to 75 °C for 1 h. The mixture was then cooled to room temperature and stirred for an additional 6 h. The precipitate was filtered and dried under house vacuum at 25 °C for 2 h to afford the desired product, Frag B (13.2 g, 57% yield; purity by qNMR: 99%; GC-MS TIC A%: 100%; wt% by comparison with a known standard: 100%; KF: 0.20%).
¹H NMR (600 MHz, CDCl₃) δ 7.83 (d, J = 7.6 Hz, 1H), 6.99 (d, J = 7.6 Hz, 1H), 5.41 (q, J = 8.6 Hz, 2H), 1.37 (s, 12H).
¹³C NMR (151 MHz, CDCl₃) δ 148.5, 145.9, 138.7, 130.9, 124.4 (q, ¹JCF3 = 282.4 Hz), 119.5, 113.0, 84.6, 50.6 (q, ²JCF3 = 33.9 Hz), 24.7.
HRMS [M + H]⁺ calcd for C₁₅H₁₈BrClF₃N₃O₂·H⁺: 376.1205 amu; found: 376.1218 amu.
