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

온도

35 °C

To a solution of methyl 4-(aminocarbonyl)-3-chloro-1H-pyrrole-2-carboxylate (0.04 g, 0.197 mmol) in THF (3 mL) and water (1 mL) was added lithium hydroxide (0.047 g, 1.974 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), DIPEA (0.052 ml, 0.296 mmol), HATU (0.090 g, 0.237 mmol) and 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.061 g, 0.197 mmol). The solution was stirred for 1 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)-1H-pyrrole-2,4-dicarboxamide (0.020 g, 21% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 12.18 (br. s., 1H) 8.15 (t, 1H) 7.83 (d, 1H) 7.46-7.56 (m, 4H) 7.37 (t, 1H) 7.30 (br. s., 1H) 7.05 (br. s., 1H) 4.57 (d, 2H). MS: m/z 481.0 (M+1).

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

ORD 기록

ord-888f1925d36b47efacdc9a076629025f

출처 데이터셋

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08304419B2