Dimethylformamide → Ammonium Hydroxide

Participants

Reaction Conditions

Reaction Steps

A flask is charged with 3-methyl-2-pyridin-3-yl-1H-indole-5-carbonitrile (Example 6, 0.200 g, 0.856 mmol) and DMF (10 mL). The mixture is cooled to 0° C. and 60% NaH in mineral oil (0.086 g, 2.14 mmol) is added. The mixture is stirred at room temperature for 20 min followed by addition of 2,2-dimethyl-propionic acid chloromethyl ester (0.310 mL, 2.14 mmol). After stirring at room temperature for 1.5 h, the mixture is diluted with ethyl acetate and washed with water. The organic layer is dried over sodium sulfate and concentrated in vacuo. The residue is purified by reverse phase HPLC with Xbridge Shield RP18 column and a 0.1% aqueous NH4OH in acetonitrile gradient to afford 2,2-dimethyl-propionic acid 5-cyano-3-methyl-2-pyridin-3-yl-indol-1-ylmethyl ester product as a white solid. 1H NMR (400 MHz, MeOD) δ ppm 1.12 (s, 9H), 2.31 (s, 3H), 6.10 (s, 2H), 7.62 (dd, J=8.5, 1.6 Hz, 1H), 7.68 (ddd, J=7.9, 5.0, 0.8 Hz, 1H), 7.81 (d, J=8.6 Hz, 1H), 8.04 (dt, J=8.1, 2.0, 1.8 Hz, 1H), 8.09 (d, J=1.0 Hz, 1H), 8.66-8.76 (m, 2H). HRMS (ESI) m/z 348.1700 [(M+H)+ Calcd for C21H22N3O2: 348.1712].

Provenance & Evidence