3-Fluoroaniline → 1-(3-fluoro-phenyl)-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide

HRID 1093784Notes

Reaction equation

HRID 1093784 reaction equation
CCN(C(C)C)C(C)C.[F:10][C:11]1[CH:12]=[C:13]([N:17]2[CH:21]=[C:20]([C:22]([OH:24])=O)[N:19]=[N:18]2)[CH:14]=[CH:15][CH:16]=1.FC1C=C(C=CC=1)N.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[NH2:55][CH2:56][C:57]([N:59]1[CH2:64][CH2:63][CH:62]([O:65][C:66]2[CH:71]=[C:70]([F:72])[CH:69]=[CH:68][C:67]=2[Cl:73])[CH2:61][CH2:60]1)=[O:58]>CN(C=O)C.O>[Cl:73][C:67]1[CH:68]=[CH:69][C:70]([F:72])=[CH:71][C:66]=1[O:65][CH:62]1[CH2:63][CH2:64][N:59]([C:57](=[O:58])[CH2:56][NH:55][C:22]([C:20]2[N:19]=[N:18][N:17]([C:13]3[CH:14]=[CH:15][CH:16]=[C:11]([F:10])[CH:12]=3)[CH:21]=2)=[O:24])[CH2:60][CH2:61]1

Participants

9

Reactant 6

HCID 97423-FluoroanilineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 28743195HCID 28743195, compoundHCID 665915752-Amino-1-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-ethanone hydrochloride

Product 1

HCID 578743771-(3-fluoro-phenyl)-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amideYield 92.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (168 mg, 1.3 mmol) was added to a stirred solution of 1-(3-fluoro-phenyl)-1H-[1,2,3]triazole-4-carboxylic acid (60 mg, 0.29 mmol) (prepared by the method used for the synthesis of Intermediate 64, starting from 3-fluoroaniline) in DMF (5 mL) followed by HOBt (43 mg, 0.32 mmol) and EDCI (139 mg, 0.72 mmol). After 2 minutes of stirring, 2-amino-1-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (103 mg, 0.32 mmol) was added and the resulting mixture was stirred at ambient temperature overnight. Cold water was then added and the solid was collected to afford 128 mg (92.75% Yield) of 1-(3-fluoro-phenyl)-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 476, 96.08%. 1H NMR (300 MHz, DMSO-d6): δ 9.4 (s, 1H), 8.54 (t, 1H), 8.0-7.96 (t, 2H), 7.72 (q, 1H), 7.54-7.34 (m, 2H), 7.34 (d, 1H), 6.9 (t, 1H), 4.9 (s, 1H), 4.3 (d, 2H), 3.8 (bs, 2H), 3.55 (bs, 2H), 2.05 (d, 2H), 1.8 (d, 2H).

Workup

  1. customprepared by the method
  2. stirringthe resulting mixture was stirred at ambient temperature overnight
  3. customthe solid was collected

Sources & evidence

ORD record
ord-2e2509fcf3bd437d96373f78d3587f7d
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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