Diisopropylamine → HCID 59425630, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of (i-Pr)2NH (1.35 mL, 9.65 mmol) in THF (30 mL) cooled to −78° C. was added n-BuLi (3.7 mL, 2.5M in hexanes, 9.21 mmol) in one portion. The acetone/dry ice bath was exchanged for ice/water bath and the solution was stirred further for 40 min. The solution was cooled to −78° C. and solution of 1-butyl-6-methoxy-1H-indole-3-carbonitrile, prepared as in example 1A (2.0 g, 8.77 mmol) in THF (10 mL) was added dropwise. This solution was stirred for 15 min at −78° C., following by 20 min at −20° C. Trimethyl borate (1.0 mL, 8.77 mmol) was added, the reaction mixture was stirred for 15 min at −20° C. after which the cooling bath was removed and this solution was stirred further at room temperature for 1 h. A solution of K3PO4 was added (11.7 mL, 3M aqueous solution, 35.1 mmol) followed by a solution of 4-iodoaniline (2.5 g, 11.40 mmol) and PdCl2dppf catalyst (640 mg, 0.88 mmol) in DMF (40 mL, plus a 5 mL rinse). The reaction mixture was stirred overnight (ca. 18 h.) and then water (80 mL) was added and the product was extracted with EtOAc (3×50 mL). The combined organic fractions were dried over MgSO4, filtered and concentrated under reduced pressure. The crude product was purified via flush chromatography on silica gel (5→60% EtOAc/Hexanes as eluant) to afford the desired 2-(4-aminophenyl)-1-butyl-6-methoxy-1H-indole-3-carbonitrile as a tan solid (2.4 g, 86% yield).

Provenance & Evidence