Piperidine → N-(Piperidin-1-yl)-4,5-di(4-methylphenyl)-1-methylimidazole-2-carboxamide

HRID 2101692Notes

Reaction equation

HRID 2101692 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([C:21](O)=[O:22])[N:11]([CH3:20])[C:12]=2[C:13]2[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=2)=[CH:4][CH:3]=1.[NH2:24][N:25]1[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1.N1CCCCC1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl.O>[N:25]1([NH:24][C:21]([C:10]2[N:11]([CH3:20])[C:12]([C:13]3[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=3)=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([CH3:1])=[CH:3][CH:4]=3)[N:9]=2)=[O:22])[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1

Participants

8

Reactant 5

HCID 8082PiperidineHCID 166581-AminopiperidineHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 22066080HCID 22066080, compound

Product 1

HCID 10157119N-(Piperidin-1-yl)-4,5-di(4-methylphenyl)-1-methylimidazole-2-carboxamideYield 32.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 4,5-di-(4-methylphenyl)-1-methylimidazole-2-carboxylic acid (25 mg, 0.08 mmol) from Step A, 1-aminopiperidine (0.020 mL, 0.16 mmol) (containing a small percent of piperidine as an impurity), PyBOP (NovaChem) (65 mg, 0.1 mmol) and DIPEA (0.025 mL, 0.1 mmol) in methylene chloride (1 mL) was stirred at rt for 20 hr. The reaction was diluted with water and extracted twice with methylene chloride. The organic layers were washed with brine, dried over sodium sulfate, and evaporated. The residue was purified twice by prep TLC (1 mm, silica gel) eluting with 5% methylene chloride, 35% ethyl acetate in hexanes to afford the primary product N-(piperidin-1-yl)-4,5-di-(4-methylphenyl)-1-methylimidazole-2-carboxamide (10 mg, 32%) and 2-(piperidin-1-ylcarbonyl)-4,5-di-(4-methylphenyl)-1-methylimidazole as a byproduct.

Workup

  1. extractionextracted twice with methylene chloride
  2. washThe organic layers were washed with brine
  3. dry with materialdried over sodium sulfate
  4. customevaporated
  5. customThe residue was purified twice by prep TLC (1 mm, silica gel)
  6. washeluting with 5% methylene chloride, 35% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-72cf6bec0a634632bec0e6ff280f84cd
Source dataset
uspto-grants-2009_08
Patent number
US07572785B2

Reaction notes

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