Lithium Hydroxide → 3-chloro-N2-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-N4,N4-dimethyl-1H-pyrrole-2,4-dicarboxamide

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl 3-chloro-4-[(dimethylamino)carbonyl]-1H-pyrrole-2-carboxylate (0.038 g, 0.165 mmol) in THF (3 mL) and water (1 mL) was added lithium hydroxide (0.039 g, 1.648 mmol). The reaction mixture was stirred overnight at 35° C. The solvent was evaporated and the resulting solid placed under high vacuum. To the intermediate mixture was added DMF (1 mL), HATU (0.075 g, 0.198 mmol), DIPEA (0.043 ml, 0.247 mmol) and 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.051 g, 0.165 mmol). The solution was stirred for 2 h at RT. Purication was accomplished by HPLC. The desired fractions were neutralized with saturated sodium bicarbonate, extracted with EtOAc (3×5 mL), the organic layers combined, dried over sodium sulfate, filtered and evaporated to afford 3-chloro-N2-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-N4,N4-dimethyl-1H-pyrrole-2,4-dicarboxamide (0.0053 g, 6% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 12.16 (br. s., 1H) 8.13 (t, 1H) 7.83 (d, 1H) 7.46-7.54 (m, 3 H) 7.38 (t, 1H) 7.16 (d, 1H) 4.56 (d, 2H) 2.95 (s, 6H). MS: m/z 509.1 (M+1).

Provenance & Evidence