Toluene → N-[5-(6-chloro-3-cyano-1-methyl-1H-indol-2-yl)-pyridin-3-ylmethyl]-ethanesulfonamide

Participants

Reaction Conditions

Reaction Steps

6-Chloro-2-(5-formyl-pyridin-3-yl)-1-methyl-1H-indole-3-carbonitrile (Example 126b, 2.0 g, 6.09 mmol), ethanesulfonamide (1.33 g, 12.17 mmol) and toluene (250 mL), and titanium(IV) isopropoxide (2.59 g, 9.13 mmol) is added dropwise. The mixture is stirred at 120° C. overnight. The mixture is then concentrated in vacuo. The residue is taken up in DCM (150 mL) and MeOH (150 mL), and NaBH4 (0.461 g, 12.17 mmol) is added at 0° C. The mixture is stirred at 0° C. for 30 min. Water (50 mL) is added and the mixture is stirred for 5 min. The suspension is filtered through a pad of celite. The celite layer is washed with DCM (3×50 mL). The combined organic phase is dried over Na2SO4 and concentrated to give a residue is purified by silica gel flash chromatography (ethyl acetate). The resulting fractions containing the product are concentrated and repurified by silica gel flash chromatography (dichloromethane-methanol, 1:0 to 97:3). The concentrated product is redissolved in MeOH (500 mL) at 60° C. and concentrated in vacuo to give N-[5-(6-chloro-3-cyano-1-methyl-1H-indol-2-yl)-pyridin-3-ylmethyl]-ethanesulfonamide. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.20 (t, J=7.3 Hz, 3H), 3.06 (q, J=7.3 Hz, 2H), 3.78 (s, 3H), 4.34 (d, J=6.3 Hz, 2H), 7.37 (dd, J=8.6, 1.8 Hz, 1H), 7.73 (d, J=8.3 Hz, 1H), 7.77 (t, J=6.2 Hz, 1H), 7.97 (d, J=1.8 Hz, 1H), 8.09 (t, J=2.1 Hz, 1H), 8.78 (d, J=1.8 Hz, 1H), 8.80 (d, J=1.8 Hz, 1H). HRMS (ESI) m/z 389.0853 [(M+H)+ Calcd for C18H17ClN4O2S: 389.0839].

Provenance & Evidence