Cesium carbonate → 7-[(2,5-dichloropyridin-4-yl)amino]-2-methyl-4-(4-propan-2-ylpiperazin-1-yl)-3H-isoindol-1-one

Participants

Reaction Conditions

Reaction Steps

A mixture of 2,5-dichloro-4-iodopyridine (0.40 g, 1.46 mmol), 7-amino-2-methyl-4-(4-propan-2-ylpiperazin-1-yl)-3H-isoindol-1-one (0.421 g, 1.46 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.051 g, 0.09 mmol), cesium carbonate (0.952 g, 2.92 mmol) and palladium(II) acetate (0.013 g, 0.06 mmol) was suspended in DMA (15 mL). The mixture was heated at 100° C. for 1 hour in a microwave reactor and then allowed to cool to room temperature. The mixture was loaded onto an SCX column and the product eluted first with MeOH and then with a 7M solution of NH3 in MeOH. Fractions containing product were combined and evaporated to afford 7-[(2,5-dichloropyridin-4-yl)amino]-2-methyl-4-(4-propan-2-ylpiperazin-1-yl)-3H-isoindol-1-one (0.630 g, 99% yield); 1H NMR spectrum: (300 MHz, DMSO) δ 1.01-1.18 (3H, d), 2.60-2.64 (4H, m), 3.04-3.09 (5H, m), 4.51 (2H, s), 7.16 (1H, d), 7.29 (1H, s), 7.50 (1H, d), 8.28 (1H, s), 9.59 (1H, s); Mass spectrum: m/z (ESI+) (M+H)=434.0 and 436.0 and 438.0.

Provenance & Evidence