Diisopropylethylamine → 2-(3-Fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (5-methoxy-3-methyl-indol-1-yl)-amide

Participants

Reaction Conditions

Reaction Steps

A microwave vial (20 mL) is charged with 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (657 mg, 2.83 mmol), HOTT (1.16 g, 3.11 mmol), DIPEA (1.35 mL, 7.73 mmol) and DMF (6 mL). The mixture is stirred at 23° C. under N2 for 15 min. 5-Methoxy-3-methyl-indol-1-ylamine (456 mg, 2.59 mmol) is added and the vial is capped. The resulting mixture is heated in a microwave (Biotage-Initiator) at 150° C. for 6 min. The mixture is portioned between EtOAc and water. The organic phase is separated, washed with saturated aqueous NaHCO3, water and brine, dried (MgSO4), filtered and concentrated in vacuo. The residue is purified by column chromatography eluting with 45% EtOAc in heptane to afford 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (5-methoxy-3-methyl-indol-1-yl)-amide (327 mg, 32%) as a solid. MS: 391 (M+H); 1H NMR (300 MHz, d6-DMSO): δ 11.75 (s, 1H), 9.19 (s, 1H), 8.32 (d, 1H), 8.18-8.16 (m, 1H), 7.66-7.62 (m, 1H), 7.45 (td, 1H), 7.30 (d, 1H), 7.22 (s, 1H), 7.05 (d, 1H), 6.85 (dd, 1H), 3.81 (s, 3H), 2.76 (s, 3H), 2.27 (s, 3H).

Provenance & Evidence