Hydrochloric Acid → N-[2-(7-methyl-1H-indazol-5-yl)-1-[1-(pyridin-2-ylmethyl)imidazol-2-yl]ethyl]-4-(2-oxo-1,4-dihydroquinazolin-3-yl)piperidine-1-carboxamide

温度

0 °C

tert-Butyl 2-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)-1-(1-(pyridin-2-ylmethyl)-1H-imidazol-2-yl)ethylcarbamate (35.2 mg, 0.063 mmol) was dissolved in a minimum amount of ethyl acetate, and treated with hydrochloric acid (4 N in dioxane, 1.0 mL). The mixture was stirred under nitrogen overnight. After removal of the solvents, the crude mixture was treated with diethyl ether to give a precipitate which was filtered. The resulting solid was dissolved in dimethylformamide (1.0 mL), cooled to 0° C., and treated with carbonyl diimidazole (11.0 mg, 0.066 mmol, 1.05 equiv) and diisopropylethylamine (44.0 μL, 4.0 equiv). The reaction was stirred for 5 min at 0° C., warmed to room temperature, stirred for 10 min, and treated with 3-(piperidin-4-yl)-3,4-dihydroquinazolin-2(1H)-one (17.6 mg, 0.066 mmol, 1.05 equiv). The mixture was stirred at room temperature overnight. The solvent was evaporated and the residue purified by column chromatography to afford 4.6 mg (12%, 2 steps). 1H-NMR (CD3OD, 500 MHz) δ 1.48-1.65 (m, 4H), 2.03 (s, 1H), 2.45 (s, 3H), 2.69-2.82 (m, 2H), 3.99-4.16 (m, 2H), 4.19 (s, 2H), 5.24 (d, J=16.5, 1H), 6.67 (d, J=7.6, 1H), 6.80 (d, J=7.9, 1H), 6.89 (s, 1H), 6.97 (dd, J=8.2, 7.6, 1H), 7.10-7.23 (m, 5H), 7.30 (s, 1H), 7.37-7.42 (m, 1H), 7.94 (s, 1H). Mass spec.: 590.3 (MH)+.

1. customAfter removal of the solvents
2. additionthe crude mixture was treated with diethyl ether
3. customto give a precipitate which
4. filtrationwas filtered
5. dissolutionThe resulting solid was dissolved in dimethylformamide (1.0 mL)
6. stirringThe reaction was stirred for 5 min at 0° C.
7. temperaturewarmed to room temperature
8. stirringstirred for 10 min
9. stirringThe mixture was stirred at room temperature overnight
10. customThe solvent was evaporated
11. customthe residue purified by column chromatography
12. customto afford 4.6 mg (12%, 2 steps)

ORDレコード

ord-e7bca9db7e594b22bb86813808f18786

出典データセット

uspto-grants-2009_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07569578B2