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

HRID 1093786Notes

Reaction equation

HRID 1093786 reaction equation
CCN(C(C)C)C(C)C.[C:10]1([CH3:24])[CH:15]=[CH:14][CH:13]=[C:12]([N:16]2[CH:20]=[C:19]([C:21]([OH:23])=O)[N:18]=[N:17]2)[CH:11]=1.CC1C=C(C=CC=1)N.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[NH2:54][CH2:55][C:56]([N:58]1[CH2:63][CH2:62][CH:61]([O:64][C:65]2[CH:70]=[C:69]([F:71])[CH:68]=[CH:67][C:66]=2[Cl:72])[CH2:60][CH2:59]1)=[O:57]>CN(C=O)C.O>[Cl:72][C:66]1[CH:67]=[CH:68][C:69]([F:71])=[CH:70][C:65]=1[O:64][CH:61]1[CH2:62][CH2:63][N:58]([C:56](=[O:57])[CH2:55][NH:54][C:21]([C:19]2[N:18]=[N:17][N:16]([C:12]3[CH:11]=[C:10]([CH3:24])[CH:15]=[CH:14][CH:13]=3)[CH:20]=2)=[O:23])[CH2:59][CH2:60]1

Participants

9

Reactant 6

HCID 7934m-ToluidineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 287432311-(3-methylphenyl)-1H-1,2,3-triazole-4-carboxylic acidHCID 665915222-Amino-1-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-ethanone

Product 1

HCID 578743761-m-tolyl-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amideYield 75.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (171 mg, 1.32 mmol) was added to a stirred solution of 1-m-tolyl-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-methylaniline) in DMF (5 mL) followed by HOBt (44 mg, 0.32 mmol) and EDCI (141 mg, 0.73 mmol). After 2 minutes of stirring, 2-amino-1-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-ethanone (105 mg, 0.32 mmol) was added and the resulting mixture was stirred at ambient temperature overnight. Cold water was then added and the precipitate was collected The solid obtained was purified by recrystallisation from a solvent system EtOAc:hexane:MeOH (2:8:0.2) to afford 103 mg (74.1% Yield) of 1-m-tolyl-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]+: 472, 96.02%. 1H NMR (300 MHz, DMSO-d6): δ 8.5 (t, 1H), 7.86 (s, 1H), 7.8 (d, 1H), 7.54-7.44 (m, 2H), 7.38-7.24 (m, 4H), 6.88 (t, 1H), 4.9 (m, 1H), 4.3 (d, 2H), 3.8 (m, 2H), 3.5 (s, 2H), 2.4 (s, 3H), 2.1 (d, 2H), 1.8 (d, 2H).

Workup

  1. customprepared by the method
  2. stirringthe resulting mixture was stirred at ambient temperature overnight
  3. customthe precipitate was collected The solid
  4. customobtained
  5. customwas purified by recrystallisation from a solvent system EtOAc:hexane:MeOH (2:8:0.2)

Sources & evidence

ORD record
ord-5586a24d72444a048f9cbf8d485b415b
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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