Oxalyl chloride → 6-chloro-N5-(1-cyanocyclopropyl)-1-ethyl-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,5-dicarboxamide

温度

40 °C

6-Chloro-1-ethyl-2-({2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}carbamoyl)-1H-indole-5-carboxylic acid (93% pure; 0.116 g, 0.22 mmol) was dissolved in dichloromethane (2.5 ml). N,N-Dimethylformamide (1 drop) and oxalyl chloride (0.058 ml, 0.66 mmol) were successively added dropwise. The reaction mixture was stirred at room temperature for 30 min and at 40° C. for 30 min, and then the solvent was removed under reduced pressure. The residue was dissolved in dichloromethane (2.5 ml) and added dropwise at room temperature to a solution of 1-aminocyclopropanecarbonitrile hydrochloride (0.052 g, 0.44 mmol) and diisopropylethylamine (0.085 g, 0.66 mmol) in dichloromethane (2.5 ml). The reaction mixture was stirred at room temperature for 16 h and then ethyl acetate was added. The organic phase was washed with saturated ammonium chloride solution and the aqueous phase was extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulphate and the solvent was removed under reduced pressure. The residue was chromatographed with water and acetonitrile through RP silica gel and gave 0.033 g (24% of theory) of 6-chloro-N5-(1-cyanocyclopropyl)-1-ethyl-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,5-dicarboxamide.

1. customthe solvent was removed under reduced pressure
2. dissolutionThe residue was dissolved in dichloromethane (2.5 ml)
3. stirringThe reaction mixture was stirred at room temperature for 16 h
4. washThe organic phase was washed with saturated ammonium chloride solution
5. extractionthe aqueous phase was extracted twice with ethyl acetate
6. dry with materialThe combined organic phases were dried over sodium sulphate
7. customthe solvent was removed under reduced pressure
8. customThe residue was chromatographed with water and acetonitrile through RP silica gel

ORDレコード

ord-fec6637052124d0ca30214f834c601fa

出典データセット

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09107411B2