F[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([C:10]([F:13])([F:12])[F:11])[C:3]=1[C:14]#[C:15][Si](C)(C)C.[NH2:20][C@@H:21]([CH3:26])[C:22]([CH3:25])([OH:24])[CH3:23].CCN(C(C)C)C(C)C.NC1C=CC=CC=1.N1C2C(=CC=CC=2)C=C1.CC([O-])(C)C.[K+]>CN1C(=O)CCC1>[OH:24][C:22]([CH3:25])([CH3:23])[C@@H:21]([N:20]1[C:2]2[C:3](=[C:4]([C:10]([F:13])([F:12])[F:11])[C:5]([C:6]#[N:7])=[CH:8][CH:9]=2)[CH:14]=[CH:15]1)[CH3:26]4-Fluoro-2-(trifluoromethyl)-3-((trimethylsilyl)ethynyl)benzonitrile (0.063 g, 0.221 mmol), (S)-3-amino-2-methylbutan-2-ol (0.060 g, 0.582 mmol) and DIEA (0.077 mL, 0.442 mmol) were combined in NMP (0.5 mL) and heated to 90° C. LCMS after heating for 9 h showed good conversion to the aniline intermediate and some desired indole formation. The mixture was cooled to rt and then treated with KOtBu (1.98 mL, 1 M in THF). The base did not afford conversion to the desired indole despite heating. The mixture was quenched with sat. aqueous NH4Cl, and then extracted with EtOAc. The combined organic fractions were concentrated to a yellow oil and then diluted with NMP (1 mL). Addition of more KOtBu (1.98 mL, 1 M in THF) afforded a dark brown solution that was heated to 50° C. LCMS after 0.5 h showed conversion to the desired indole. The reaction was again quenched with sat. aqueous NH4Cl and then extracted with EtOAc. The combined organic portions were concentrated to a yellow oil and then chromatographed (ISCO, std grad, hex/EtOAc, 24 g silica) to afford the desired product. The mixture was next subjected to reverse phase semiprep (Agilent, 230 nm detection) to afford the desired product as a colorless gum: MS (ESI): m/z 297 (MH+).
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