N-methyl-2-pyrrolidone → methyl 3-((4-(7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxamido)-1H-indazol-1-yl)methyl)benzoate

A mixture of lithium 7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxylate (0.09578 g, 0.2933 mmol) and NMP (1.5 mL) were warmed to provide a homogeneous solution and then cooled to ambient temperature. 2,4,6-Trichlorobenzoyl chloride (0.04277 mL, 0.2737 mmol) was added and the mixture stirred at ambient temperature for 0.5 hours. Methyl 3-((4-amino-1H-indazol-1-yl)methyl)benzoate (0.055 g, 0.1955 mmol) was added as a NMP solution (1.5 mL) and the mixture was heated to 80° C. and stirred for 4 hours. The mixture was dissolved in MeOH and concentrated. The residue was dissolved in saturated aqueous NaHCO3 and EtOAc and the organic layer was washed with brine and dried over Na2SO4. The crude material was purified by column chromatography (15% MeOH/CH2Cl2 adding 1% 7N NH3/MeOH) to provide methyl 3-((4-(7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxamido)-1H-indazol-1-yl)methyl)benzoate as the free base. This material was dissolved in MeOH (3.0 mL) and CHCl3 (1.0 mL), and HCl (1.955 mL, 3.910 mmol, 2.0M Et2O) was added and the mixture was stirred for 2 hours and then concentrated. The resulting solid was washed with Et2O and then with hexanes, and dried under vacuum to afford 0.085 g (64%) of the title compound. MS (ES+APCI) m/z=568 (M+H-2HCl).

1. temperaturewere warmed
2. customto provide a homogeneous solution
3. temperaturethe mixture was heated to 80° C.
4. stirringstirred for 4 hours
5. concentrationconcentrated
6. dissolutionThe residue was dissolved in saturated aqueous NaHCO3
7. washEtOAc and the organic layer was washed with brine
8. dry with materialdried over Na2SO4
9. customThe crude material was purified by column chromatography (15% MeOH/CH2Cl2 adding 1% 7N NH3/MeOH)

ORD 기록

ord-a2f778caadb247d1b3f1a385ffa75deb

출처 데이터셋

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09174981B2