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

HRID 1093782Notes

Reaction equation

HRID 1093782 reaction equation
CCN(C(C)C)C(C)C.[C:10]1([N:16]2[CH:20]=[C:19]([C:21]([OH:23])=O)[N:18]=[N:17]2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[ClH:45].[NH2:46][CH2:47][C:48]([N:50]1[CH2:55][CH2:54][CH:53]([O:56][C:57]2[CH:62]=[CH:61][CH:60]=[C:59](C(F)(F)F)[CH:58]=2)[CH2:52][CH2:51]1)=[O:49]>CN(C=O)C.O>[Cl:45][C:58]1[CH:59]=[CH:60][CH:61]=[CH:62][C:57]=1[O:56][CH:53]1[CH2:54][CH2:55][N:50]([C:48](=[O:49])[CH2:47][NH:46][C:21]([C:19]2[N:18]=[N:17][N:16]([C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH:20]=2)=[O:23])[CH2:51][CH2:52]1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 5551941-Phenyl-1H-1,2,3-triazole-4-carboxylic acidHCID 665915472-Amino-1-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethanone hydrochloride

Product 1

HCID 578743841-phenyl-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amideYield 50%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (137 mg, 11.0 mmol) was added to stirred solution of 1-phenyl-1H-[1,2,3]triazole-4-carboxylic acid (50 mg, 0.26 mmol) in DMF (3 mL) followed by HOBT (39 mg, 0.29 mmol) and EDCI (100 mg, 0.53 mmol). After 2 minutes of stirring, 2-amino-1-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (prepared according to Step 1 and 5 of the General Scheme) (90 mg, 0.26 mmol) was added and the resulting mixture was stirred at room temperature overnight. The reaction mixture was diluted with cold water and extracted with ethyl acetate. The organic layer collected was dried over sodium sulfate and concentrated under reduced pressure afforded residue. The residue was purified by column chromatography (using 60-120 silica gel and 50% EtOAc in hexane as eluent) afforded 63 mg (50% Yield) of 1-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]+: 474.14, 94.1%. 1H NMR (300 MHz, DMSO-d6): δ 9.38 (s, 1H), 8.5 (t, 1H), 8.0 (d, 2H), 7.7-7.6 (t, 2H), 7.6-7.5 (t, 2H), 7.36-7.24 (t, 3H), 4.8 (q, 1H), 4.25 (d, 2H), 4.0-3.8 (m, 1H), 3.8-3.7 (m, 1H), 3.5 (m, 2H), 2.0 (m, 2H), 1.8-1.5 (m, 2H).

Workup

  1. additionwas added
  2. stirringthe resulting mixture was stirred at room temperature overnight
  3. extractionextracted with ethyl acetate
  4. customThe organic layer collected
  5. dry with materialwas dried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customafforded residue
  8. customThe residue was purified by column chromatography (using 60-120 silica gel and 50% EtOAc in hexane as eluent)

Sources & evidence

ORD record
ord-d6f56e9a08b142d5b9311ee3befd7c66
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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