Trifluoroacetic acid → 2-((3-(4-(1-Acetylazetidin-3-yl)piperazin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

温度

50 °C

To a solution of 2-((3-(4-(1-acetylazetidin-3-yl)piperazin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (110 mg, 0.169 mmol) in DCE (1.1 mL) and anisole (0.108 mL, 0.985 mmol) was added TFA (0.296 mL, 3.84 mmol) slowly drop wise at room temperature and the reaction mixture was heated at 50° C. for overnight. The reaction mixture was concentrated to remove solvent completely; the resultant residue was washed with hexane to remove anisole. The residue was diluted with Ethyl acetate, washed with aq. ammonia solution, brine, dried over Na2SO4 and concentrated. The crude material was purified by reverse phase HPLC, the fractions were concentrated and the resultant solid was dissolved in HPLC grade Chloroform (20 ml), washed with 10% NaHCO3 solution, brine, dried over Na2SO4 and concentrated. The solid was dissolved in Acetonitrile/water (1:3). Froze the mixture using a dry-ice acetone bath and then dried under lyophilization for 2 days. Lyophlization afforded 2-((3-(4-(1-acetylazetidin-3-yl)piperazin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (50 mg) as a off white solid.

1. customslowly drop wise at room temperature
2. concentrationThe reaction mixture was concentrated
3. customto remove solvent completely
4. washthe resultant residue was washed with hexane
5. customto remove anisole
6. additionThe residue was diluted with Ethyl acetate
7. washwashed with aq. ammonia solution, brine
8. dry with materialdried over Na2SO4
9. concentrationconcentrated
10. customThe crude material was purified by reverse phase HPLC
11. concentrationthe fractions were concentrated
12. dissolutionthe resultant solid was dissolved in HPLC grade Chloroform (20 ml)
13. washwashed with 10% NaHCO3 solution, brine
14. dry with materialdried over Na2SO4
15. concentrationconcentrated
16. dissolutionThe solid was dissolved in Acetonitrile/water (1:3)
17. customdried under lyophilization for 2 days

ORDレコード

ord-1dea1e4a0ca1472ca5249f3d1585f383

出典データセット

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09273057B2