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

Temperature

35 °C

To a solution of methyl 3-chloro-4-[(methylamino)carbonyl]-1H-pyrrole-2-carboxylate (0.04 g, 0.185 mmol) in THF (3 mL) and water (1 mL) was added lithium hydroxide (0.044 g, 1.847 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 (0.084 g, 0.222 mmol), DIPEA (0.048 ml, 0.277 mmol) and 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.057 g, 0.185 mmol). The solution was stirred for 1.5 h at RT. Purification 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-methyl-1H-pyrrole-2,4-dicarboxamide (0.028 g, 31% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 12.14 (br. s., 1H) 8.13 (t, 1H) 7.81 (d, 1H) 7.74-7.79 (m, 1H) 7.44-7.53 (m, 3H) 7.35 (t, 1H) 7.40 (d, 1H) 4.54 (d, 2H) 2.68 (d, 3H). MS: m/z 495.1 (M+1).

1. customThe solvent was evaporated
2. stirringThe solution was stirred for 1.5 h at RT
3. customPurification
4. extractionextracted with EtOAc (3×5 mL)
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. customevaporated

ORD record

ord-8bc1f13c544d4f32b3f772da814cb1d9

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08304419B2