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With sodium cyanoborohydride; acetic acid; at -10 - 20℃;
Steps 1-3 A solution of <strong>[248602-16-6]6-bromo-5-methylindole</strong> (1.00 g, 4.75 mmol) in AcOH (150 mL) was treated with NaBH3CN (0.897 g, 14.3 mmol) while maintaining a temperature of -10 C. The mixture was then stirred at RT overnight and concentrated. The resulting residue was treated with aqueous K2CO3, and extracted with DCM (3×100 mL). The combined organic layers were dried over MgSO4, concentrated and purified by column chromatography (0-75% EtOAc/hexanes) to afford 6-bromo-5-methylindoline (13A, 716 mg).
The title compound is prepared according to General Procedure 14 described for Intermediate 45, using 6-bromo-5-methyl-1 /-/-indole (250 mg; 1.19 mmol; 1 eq.), NaH (60% in mineral oil, 95 mg; 2.38 mmol; 2 eq.), iodomethane (338 mg; 2.38 mmol; 2 eq.) in dry THF (5 ml_). Conditions: 0 C to room temperature for 15 h. The crude 6-bromo-1 ,5-dimethyl-1 /-/-indole (269 mg; 0.9 mmol; 76%; UPLC purity: 75%) is used in the next step without further purification.
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine at 70 - 100℃; for 16h;
22.1
To a solution of 6-bromo-5-methyl-lH-indole (500 mg, 2.38 mmol) in MeOH (5 mL) was added TEA (9.63 g, 95.21 mmol, 13.25 mL) and Pd(dppf)Cl2 (348.31 mg, 476.03 umol) under a N2 atmosphere. The suspension was degassed and purged with CO (3x). The mixture was stirred at 70 °C for 12 hr under CO (50 psi), then it was warmed to 100 °C and stirred for another 4 hr under CO atmosphere (3 Mpa). The reaction mixture was concentrated and purified by flash silica gel chromatography (ISCO; 12 g SepaFlash Silica Flash Column, eluent of 0~8% EtoAc/petroleum ether gradient at 80 mL/min) to afford the title compound (40 mg, 211.41 umol, 8.88% yield) as a yellow solid.
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