1-Aminopiperidine → 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-n-(piperidin-1-yl)-1h-1,2,4-triazole-3-carboxamide hydrochloride

HRID 2251711Notes

Reaction equation

HRID 2251711 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=3[Cl:20])[N:11]=[C:10]([C:21]([OH:23])=O)[N:9]=2)=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)[C:44]2[CH:45]=[CH:46][CH:47]=C[C:43]=2[N:42]=[N:41]1.NN1CCCCC1.C([O-])(O)=O.[Na+]>C(#N)C>[ClH:1].[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=3[Cl:20])[N:11]=[C:10]([C:21]([NH:41][N:42]3[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]3)=[O:23])[N:9]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 166581-AminopiperidineHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 111528615-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-1H-1,2,4-triazole-3-carboxylic acid

Product 1

HCID 117551855-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-n-(piperidin-1-yl)-1h-1,2,4-triazole-3-carboxamide hydrochlorideYield 153.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Part D: To a stirred solution of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-1H-1,2,4-triazole-3-carboxylic acid (1.48 gram, 4.0 mmol) in acetonitrile (20 mL) is successively added diisopropylethylamine (DIPEA) (1.5 mL, 2.1 molar equivalent), O-benzotriazol-1-yl-N,N, N′,N′-tetramethyluronium hexafluorophosphate (HBTU) (1.66 gram, 1.1 molar equivalent) and 1-aminopiperidine (0.44 gram, 1.1 molar equivalent). After stirring overnight an aqueous NaHCO3 solution is added. The resulting mixture is three times extracted with dichloromethane. The combined organic layers are washed with water, dried over Na2SO4, filtered and concentrated in vacuo to give a crude oil (3.6 gram). This oil is further purified by flash chromatography (silica gel; EtOAc/petroleum ether (40-60° C.)=7/3 (v/v)). The purified material is treated with ethanolic HCl (1M solution) to give 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-N-(piperidin-1-yl)-1H-1,2,4-triazole-3-carboxamide hydrochloride (1.50 gram, 77% yield). Melting point: 238-240° C. (decomposition). 1H-NMR (400 MHz, DMSO-d6): δ 1.46-1.54 (m, 2H), 1.78-1.85 (m, 4H), 3.22-3.28 (m, 4H), 7.50 (s, 4H), 7.70 (dd, J=8 and 2 Hz, 1H), 7.85-7.87 (m, 1H), 7.91 (d, J=8 Hz, 1H), (NH not visible).

Workup

  1. additionis added
  2. extractionextracted with dichloromethane
  3. washThe combined organic layers are washed with water
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give a crude oil (3.6 gram)
  8. customThis oil is further purified by flash chromatography (silica gel; EtOAc/petroleum ether (40-60° C.)=7/3 (v/v))
  9. additionThe purified material is treated with ethanolic HCl (1M solution)

Sources & evidence

ORD record
ord-99acd36c0a05444c8a2344efe79e6de7
Source dataset
uspto-grants-2008_01
Patent number
US07319110B2

Reaction notes

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