1-Hydroxybenzotriazole → ethyl 2-[({[4-({cyclohexyl[1-(3-ethoxyphenyl)-3-ethyl-1H-pyrazol-4-yl]methyl}amino)phenyl]carbonyl}amino)methyl]-2-ethylbutanoate

HRID 2090974Notes

Reaction equation

HRID 2090974 reaction equation
[CH:1]1([CH:7]([NH:24][C:25]2[CH:33]=[CH:32][C:28]([C:29](O)=[O:30])=[CH:27][CH:26]=2)[C:8]2[C:9]([CH2:22][CH3:23])=[N:10][N:11]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH2:20][CH3:21])[CH:14]=3)[CH:12]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.Cl.[NH2:57][CH2:58][C:59]([CH2:67][CH3:68])([CH2:65][CH3:66])[C:60]([O:62][CH2:63][CH3:64])=[O:61]>CN(C)C=O.O.C(N(CC)CC)C>[CH:1]1([CH:7]([NH:24][C:25]2[CH:33]=[CH:32][C:28]([C:29]([NH:57][CH2:58][C:59]([CH2:65][CH3:66])([CH2:67][CH3:68])[C:60]([O:62][CH2:63][CH3:64])=[O:61])=[O:30])=[CH:27][CH:26]=2)[C:8]2[C:9]([CH2:22][CH3:23])=[N:10][N:11]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH2:20][CH3:21])[CH:14]=3)[CH:12]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 14882782Ethyl 2-(aminomethyl)-2-ethylbutanoate hydrochlorideHCID 667784324-({cyclohexyl[1-(3-ethoxyphenyl)-3-ethyl-1H-pyrazol-4-yl]methyl}amino)benzoic acid

Product 1

HCID 66777282ethyl 2-[({[4-({cyclohexyl[1-(3-ethoxyphenyl)-3-ethyl-1H-pyrazol-4-yl]methyl}amino)phenyl]carbonyl}amino)methyl]-2-ethylbutanoateYield 74.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

4-({Cyclohexyl[1-(3-ethoxyphenyl)-3-ethyl-1H-pyrazol-4-yl]methyl}amino)benzoic acid (0.18 g) synthesized in Example 92(2) was dissolved in N,N-dimethylformamide (3 mL), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.11 g), 1-hydroxybenzotriazole.monohydrate (0.09 g), ethyl 2-(aminomethyl)-2-ethylbutanoate hydrochloride (0.12 g) and triethylamine (0.09 mL) were added at room temperature, and the mixture was stirred overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:2, volume ratio) to give ethyl 2-[({[4-({cyclohexyl[1-(3-ethoxyphenyl)-3-ethyl-1H-pyrazol-4-yl]methyl}amino)phenyl]carbonyl}amino)methyl]-2-ethylbutanoate (0.18 g) as a yellow oil. This was dissolved in ethanol (2.0 mL), 1N aqueous sodium hydroxide solution (2.0 mL) was added at room temperature, and the mixture was stirred at 60° C. overnight. Ethanol was evaporated under reduced pressure, and 1N hydrochloric acid (2.0 mL) was added to the residue. The precipitate was washed with water to give the title object compound (0.17 g, 74%) as a colorless solid.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. concentrationThe extract was concentrated under reduced pressure
  3. customthe residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:2, volume ratio)

Sources & evidence

ORD record
ord-e4d3d0b237f2455ea1713dcfbd4c8907
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

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