1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1-(3,5-difluoro-phenyl)-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide

DIPEA (160.7 mg, 1.24 mmol) was added to a stirred solution of 1-(3,5-difluoro-phenyl)-1H-[1,2,3]triazole-4-carboxylic acid (prepared by the method used for the synthesis of Intermediate 64, starting from 3,5-difluoroaniline) (70 mg, 0.31 mmol) in DMF (2 mL) followed by HOBt (46.2 mg, 0.34 mmol) and EDCI (119 mg, 0.62 mmol). After 2 minutes of stirring, 2-amino-1-[4-(2-chloro-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (94.8 mg, 0.31 mmol) (prepared according to Step 1 and 5 of the General Scheme) was added and the resulting mixture was stirred at room temperature overnight. Cold water was added and the precipitate was collected. The crude solid was stirred in a mixture of 30% EtOAc in hexane and MeOH (0.5 mL) for 1 hr and filtered to afford 95 mg (64.19% Yield) of 1-(3,5-difluoro-phenyl)-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 476.12, 98.71%. 1H NMR (300 MHz, DMSO-d6): δ 9.5 (s, 1H), 8.5 (t, 1H), 7.9 (m, 2H), 7.6-7.4 (m, 2H), 7.4-7.2 (m, 2H), 7.0 (m, 1H), 4.8 (m, 1H), 4.2 (d, 2H), 3.8-3.6 (m, 2H), 3.6-3.4 (m, 2H), 2.1-1.8 (m, 2H), 1.8-1.5 (m, 2H).

1. customprepared by the method
2. additionwas added
3. stirringthe resulting mixture was stirred at room temperature overnight
4. customthe precipitate was collected
5. stirringThe crude solid was stirred in a mixture of 30% EtOAc in hexane and MeOH (0.5 mL) for 1 hr
6. filtrationfiltered

ORD-Eintrag

ord-101edf6cd8a14a86ad29e6d593fa4ae4

Quelldatensatz

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08129376B2