Ethyl 4-(piperazin-1-yl)benzoate → N-(1-tert-butyl-3-(3-methoxyphenethyl)-1H-pyrazol-5-yl)-4-(piperazin-1-yl)benzamide

HRID 16788Notes

Reaction equation

HRID 16788 reaction equation
C[Al](C)C.[C:5]([N:9]1[C:13]([NH2:14])=[CH:12][C:11]([CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH3:24])[CH:18]=2)=[N:10]1)([CH3:8])([CH3:7])[CH3:6].[N:25]1([C:31]2[CH:41]=[CH:40][C:34]([C:35](OCC)=[O:36])=[CH:33][CH:32]=2)[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1>C1(C)C=CC=CC=1>[C:5]([N:9]1[C:13]([NH:14][C:35](=[O:36])[C:34]2[CH:33]=[CH:32][C:31]([N:25]3[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]3)=[CH:41][CH:40]=2)=[CH:12][C:11]([CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH3:24])[CH:18]=2)=[N:10]1)([CH3:8])([CH3:7])[CH3:6]

Participants

5

Reactant 3

HCID 2761178Ethyl 4-(piperazin-1-yl)benzoateHCID 16682925TrimethylaluminumHCID 574539341-tert-butyl-3-(3-methoxyphenethyl)-1H-pyrazol-5-amine

Product 1

HCID 66589920N-(1-tert-butyl-3-(3-methoxyphenethyl)-1H-pyrazol-5-yl)-4-(piperazin-1-yl)benzamideYield 22.53%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
20 °C

Procedure

A 2M solution of trimethylaluminium in toluene (6.25 mL, 12.50 mmol) was added dropwise to a stirred solution of and 1-tert-butyl-3-(3-methoxyphenethyl)-1H-pyrazol-5-amine (1.367 g, 5.00 mmol) and ethyl 4-(piperazin-1-yl)benzoate (1.171 g, 5 mmol) in toluene (20 mL) at 4° C., over a period of 5 mins under nitrogen. The resulting solution was stirred at 20° C. for 18 h. The reaction mixture was quenched with methanol (20 mL), filtered and evaporated to afford tan solid. The crude product was purified by silica column chromatography, eluting with a gradient of 0 to 10% MeOH in DCM and 0.1% ammonia. Pure fractions were evaporated to dryness to afford N-(1-tert-butyl-3-(3-methoxyphenethyl)-1H-pyrazol-5-yl)-4-(piperazin-1-yl)benzamide (0.520 g, 22.53%) as a white solid.

Workup

  1. customThe reaction mixture was quenched with methanol (20 mL)
  2. filtrationfiltered
  3. customevaporated
  4. customto afford tan solid
  5. customThe crude product was purified by silica column chromatography
  6. washeluting with a gradient of 0 to 10% MeOH in DCM and 0.1% ammonia
  7. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-514c287ae29942239d240ba47643eabe
Source dataset
uspto-grants-2010_06
Patent number
US07737149B2

Reaction notes

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