1-Aminopiperidine → HCID 11294616, compound

HRID 2215065Notes

Reaction equation

HRID 2215065 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH2:13][F:14])=[C:11]([C:15]([OH:17])=O)[N:10]=[C:9]2[C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=2[Cl:25])=[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:46]2[CH:47]=[CH:48][CH:49]=C[C:45]=2[N:44]=[N:43]1.NN1CCCCC1>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH2:13][F:14])=[C:11]([C:15]([NH:43][N:44]3[CH2:49][CH2:48][CH2:47][CH2:46][CH2:45]3)=[O:17])[N:10]=[C:9]2[C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=2[Cl:25])=[CH:4][CH:3]=1

Participants

5

Reactant 4

HCID 166581-AminopiperidineHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11395463HCID 11395463, compound

Product 1

HCID 11294616HCID 11294616, compoundYield 64%

Procedure

Part D: 1-(4-Chlorophenyl)-2-(2,4-dichlorophenyl)-5-fluoromethyl-N-(piperidin-1-yl)-1H-imidazole-4-carboxamide. 1-(4-Chlorophenyl)-2-(2,4-dichlorophenyl)-5-fluoromethyl-N-(piperidin-1-yl)-1H-imidazole-4-carboxamide was obtained by reacting 1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-5-fluoromethyl-1H-imidazole-4-carboxylic acid (0.87 g, 2.18 mmol), diisopropylethylamine (DIPEA) (0.84 mL, 4.80 mmol), O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU) (0.99 g, 2.62 mmol) and 1-aminopiperidine (0.28 mL, 2.62 mmol) for 16 hours at room temperature. The resulting mixture was concentrated in vacuo. The residue was dissolved in ethyl acetate, successively washed with aqueous NaHCO3 solution, water and brine, dried over Na2SO4, filtered and concentrated to give a crude solid. This solid was further purified by flash chromatography. 1-(4-Chlorophenyl)-2-(2,4-dichlorophenyl)-5-fluoromethyl-N-(piperidin-1-yl)-1H-imidazole-4-carboxamide was obtained in 64% yield, mp 162–163° C.; 1H-NMR (600 MHz, DMSO-d6) δ 1.35–1.41 (m, 2H), 1.61–1.66 (m, 4H), 2.80–2.84 (m, 4H), 5.63 (d, J=48 Hz, 2H), 7.36 (d, J=8 Hz, 2H), 7.44 (dd, J=8 and 2 Hz, 1H), 7.48 (d, J=8 Hz, 2H), 7.55 (d, J=2 Hz, 1H), 7.67 (d, J=8 Hz, 1H), 9.10 (s, 1H); HRMS (C22H21Cl3FN4O) [M+H]+: found m/z 481.0760, calcd 481.0765.

Workup

  1. customfor 16 hours
  2. customat room temperature
  3. concentrationThe resulting mixture was concentrated in vacuo
  4. dissolutionThe residue was dissolved in ethyl acetate
  5. washsuccessively washed with aqueous NaHCO3 solution, water and brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a crude solid
  10. customThis solid was further purified by flash chromatography

Sources & evidence

ORD record
ord-0f86667b60734a89a3ff0ef6bf4b36c2
Source dataset
uspto-grants-2006_09
Patent number
US07109216B2

Reaction notes

Loading…