p-Toluenesulfonic acid monohydrate → HCID 71209202, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-amino-1-(3,4-difluorobenzyl)-1H-pyrrole-3-carbonitrile (20 g, 86 mmol) and toluene (700 mL) was heated to reflux eliminating 30 mL of toluene using a Dean-Stark trap then (E)-ethyl 3-ethoxybut-2-enoate (14.9 g, 94 mmol) and 4-methylbenzenesulfonic acid hydrate (1.6 g, 8.56 mmol) and were added. The mixture was heated to 155° C. for 1 h using a Dean-Stark trap to eliminate 350 mL of solvent. The mixture was cooled to 0° C. and sodium ethoxide (41.6 mL, 111 mmol, 21% wt/EtOH) was added dropwise and the mixture was heated to reflux (145° C.) for 1 h using a Dean-Stark trap to eliminate 100 mL of solvent. Water was added followed by 1M HCl/water adjusting the pH-9. The mixture was extracted with EtOAc. The organic phase was dried (Na2SO4), concentrated, and purified by column chromatography provide ethyl 4-amino-1-(3,4-difluorobenzyl)-6-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxylate (23.1 g, 66.8 mmol, 78% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.43 (t, J=7 Hz, 3 H), 2.78 (s, 3 H), 4.40 (q, J=7 Hz, 2 H), 5.36 (s, 2 H), 6.3 (br s, 2 H), 6.5 (m, 2 H), 6.6-7.2 (m, 4 H); LCMS (m/z) ES+=346 (M+1).

Provenance & Evidence