Tetrahydrofuran heptane ethylbenzol → tert-Butyl-4-((6-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indol-2-yl)(hydroxy)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indole-6-carbonitrile (424 mg, 1.55 mmol) in THF (0.7 mL), 1.8 M LDA in heptane/THF/ethylbenzene (139 mg, 1.29 mmol) was added at −78° C. The reaction was stirred at −78° C. for 30 minutes. tert-Butyl 4-formyl-5-methoxy-7-methyl-1H-indole-1-carboxylate (Example 19-D) (250 mg, 0.86 mmol) in THF (0.7 mL) was added at −78° C. The reaction was quenched with MeOH and then a saturated aq. ammonium chloride solution. The mixture was then diluted with EtOAc and the organic layer was removed, dried over MgSO4, filtered and concentrated. The resulting residue was purified via flash chromatography (0-40% EtOAc:heptanes) to obtain the title compound. 1H NMR (400 MHz, DMSO-d6) d ppm 8.06 (s, 1H) 7.61 (d, J=8.34 Hz, 1H) 7.51 (d, J=3.79 Hz, 1H) 7.34 (dd, J=8.21, 1.39 Hz, 1H) 6.91 (s, 1H) 6.79 (d, J=3.79 Hz, 1H) 6.63-6.71 (m, 1H) 6.20 (s, 1H) 6.09 (d, J=4.80 Hz, 1H) 5.57-5.74 (m, 2H) 3.81 (s, 3H) 3.40 (ddd, J=9.22, 6.82, 2.15 Hz, 2H) 2.55 (s, 3H) 1.50-1.63 (m, 9H) 0.78 (td, J=9.28, 6.95 Hz, 2H) −0.13-−0.09 (m, 9H).

Provenance & Evidence