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

HRID 1093785Notes

Reaction equation

HRID 1093785 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.Cl.[NH2:55][CH2:56][C:57]([N:59]1[CH2:64][CH2:63][CH:62]([O:65][C:66]2[CH:71]=[CH:70][CH:69]=[C:68]([C:72]([F:75])([F:74])[F:73])[CH:67]=2)[CH2:61][CH2:60]1)=[O:58]>CN(C=O)C.CO.CCCCCC.O>[O:58]=[C:57]([N:59]1[CH2:60][CH2:61][CH:62]([O:65][C:66]2[CH:71]=[CH:70][CH:69]=[C:68]([C:72]([F:75])([F:73])[F:74])[CH:67]=2)[CH2:63][CH2:64]1)[CH2:56][NH:55][C:21]([C:19]1[N:18]=[N:17][N:16]([C:12]2[CH:11]=[C:10]([CH3:24])[CH:15]=[CH:14][CH:13]=2)[CH:20]=1)=[O:23]

Participants

11

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 665915472-Amino-1-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethanone hydrochloride

Product 1

HCID 578744291-m-tolyl-1H-[1,2,3]triazole-4-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amideYield 70.5%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8058HexaneSolvent

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-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (prepared according to Step 1 and 5 of the General Scheme) (110 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 the crude solid. The crude solid obtained was purified by recrystallisation from a solvent system (3:7:0.2), EtOAc:hexane:MeOH to afford 100 mg (70.5% Yield) of 1-m-tolyl-1H-[1,2,3]triazole-4-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide. LC/MS [M+H]+: 488, 96.08%. 1H NMR (300 MHz, DMSO-d6): δ 9.3 (s, 1H), 8.5 (t, 1H), 7.84 (s, 1H), 7.8 (d, 1H), 7.56-7.44 (m, 2H), 7.38-7.24 (m, 4H), 4.8 (m, 1H), 4.2 (d, 2H), 3.9 (s, 1H), 3.8 (s, 1H), 3.5 (s, 1H), 3.3 (s, 1H), 2.4 (s, 3H), 2.1 (t, 2H), 1.8 (d, 2H).

Workup

  1. customprepared by the method
  2. additionwas added
  3. stirringthe resulting mixture was stirred at ambient temperature overnight
  4. customthe solid was collected
  5. customto afford the crude solid
  6. customThe crude solid obtained
  7. customwas purified by recrystallisation from a solvent system (3:7:0.2), EtOAc

Sources & evidence

ORD record
ord-d3013f9489194b6189303b14d644f6e6
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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