Trifluoroacetic acid → 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-(4-(4-(3-(dimethylamino)propylamino)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)phenoxy)propyl)thiazole-4-carboxylic acid

Participants

Reaction Steps

To a solution of compound 54A (160 mg, 0.512 mmol) in DMF (5 ml) was added sodium hydride (102 mg, 2.56 mmol)(60%). The reaction mixture was stirred for 10 min and Example 2C (194 mg, 0.307 mmol) was added. The resulting mixture was stirred for 1 hour and methanol (3 ml), 10% NaOH (3 ml) and water (1 ml) were added. The resulting mixture was stirred overnight, acidified with TFA and concentrated. The residue was dissolved in a mixture of DMSO-methanol and purified by reverse phase HPLC (mobile phase: 0%-55% acetonitrile in 0.1% TFA aqueous solution during 60 min) to provide the title compound: 1H NMR (400 MHz, DMSO-D6) δ ppm 12.84 (1H, s), 9.34 (1H, s), 8.53 (1H, t), 8.36 (1H, s), 8.32 (1H, s), 7.96-8.03 (3H, m), 7.78 (1H, d), 7.67 (1H, d), 7.42-7.49 (2H, m), 7.32-7.41 (2H, m), 7.05-7.10 (2H, m), 4.84 (2H, s), 4.04 (2H, t), 3.73 (2H, t), 3.60 (2H, q), 3.12-3.26 (4H, m), 3.03 (2H, t), 2.80 (6H, s), 1.93-2.08 (4H, m). LCMS (APCI) m/e 789 (M+H).

Provenance & Evidence