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

HRID 1093838Notes

Reaction equation

HRID 1093838 reaction equation
CCN(C(C)C)C(C)C.[F:10][C:11]1[CH:12]=[C:13]([N:18]2[CH:22]=[C:21]([C:23]([OH:25])=O)[N:20]=[N:19]2)[CH:14]=[C:15]([F:17])[CH:16]=1.FC1C=C(C=C(F)C=1)N.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[NH2:57][CH2:58][C:59]([N:61]1[CH2:66][CH2:65][CH:64]([O:67][C:68]2[CH:73]=[CH:72][CH:71]=[CH:70][C:69]=2[Cl:74])[CH2:63][CH2:62]1)=[O:60]>CN(C=O)C.O>[Cl:74][C:69]1[CH:70]=[CH:71][CH:72]=[CH:73][C:68]=1[O:67][CH:64]1[CH2:63][CH2:62][N:61]([C:59](=[O:60])[CH2:58][NH:57][C:23]([C:21]2[N:20]=[N:19][N:18]([C:13]3[CH:14]=[C:15]([F:17])[CH:16]=[C:11]([F:10])[CH:12]=3)[CH:22]=2)=[O:25])[CH2:66][CH2:65]1

Participants

9

Reactant 6

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 965953,5-DifluoroanilineHCID 287431861-(3,5-difluorophenyl)-1H-1,2,3-triazole-4-carboxylic acidHCID 665915282-Amino-1-[4-(2-chloro-phenoxy)-piperidin-1-yl]-ethanone hydrochloride

Product 1

HCID 578744611-(3,5-difluoro-phenyl)-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amideYield 64.19%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-101edf6cd8a14a86ad29e6d593fa4ae4
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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