2-Chloro-p-toluidine → tert-Butyl 4-(2-chloro-4-methylphenylcarbamoyl)-3-{4-cyclopropyl-5-[3-(2-ethylbutyl)cyclobutyl]isoxazol-3-yl}butanoate

HRID 1912099Notes

Reaction equation

HRID 1912099 reaction equation
[CH:1]1([C:4]2[C:5]([CH:19]([CH2:28][C:29]([O-:31])=O)[CH2:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[N:6][O:7][C:8]=2[CH:9]2[CH2:12][CH:11]([CH2:13][CH:14]([CH2:17][CH3:18])[CH2:15][CH3:16])[CH2:10]2)[CH2:3][CH2:2]1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[Cl:54][C:55]1[CH:60]=[C:59]([CH3:61])[CH:58]=[CH:57][C:56]=1[NH2:62]>C(OCC)(=O)C.O.CN(C=O)C>[Cl:54][C:55]1[CH:60]=[C:59]([CH3:61])[CH:58]=[CH:57][C:56]=1[NH:62][C:29]([CH2:28][CH:19]([C:5]1[C:4]([CH:1]2[CH2:2][CH2:3]2)=[C:8]([CH:9]2[CH2:10][CH:11]([CH2:13][CH:14]([CH2:15][CH3:16])[CH2:17][CH3:18])[CH2:12]2)[O:7][N:6]=1)[CH2:20][C:21]([O:23][C:24]([CH3:25])([CH3:27])[CH3:26])=[O:22])=[O:31]

Participants

8

Reactant 4

HCID 120072-Chloro-p-toluidineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86675055Mono-tert-butyl 3-{4-cyclopropyl-5-[3-(2-ethylbutyl)cyclobutyl]isoxazol-3-yl}glutarate

Product 1

HCID 86675054tert-Butyl 4-(2-chloro-4-methylphenylcarbamoyl)-3-{4-cyclopropyl-5-[3-(2-ethylbutyl)cyclobutyl]isoxazol-3-yl}butanoate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Mono-tert-butyl 3-{4-cyclopropyl-5-[3-(2-ethylbutyl)cyclobutyl]isoxazol-3-yl}glutarate (150 mg) and DMF (1.5 mL) were mixed. To the mixture were added HOBt.H2O (63.5 mg), WSC.HCl (79.6 mg) and 2-chloro-4-methylphenylamine (0.0512 mL). The mixture was stirred at RT overnight. To the reaction mixture was added ethyl acetate. The mixture was washed with aqueous 10 w/v % citric acid, water, saturated aqueous sodium bicarbonate and brine, then dried over sodium sulfate. The sodium sulfate was filtered off and the filtrate was concentrated in vacuo. The resultant residue was purified by preparative chromatography (Eluent: ethyl acetate/hexane=1/6) to give the title compound (122 mg).

Workup

  1. washThe mixture was washed with aqueous 10 w/v % citric acid, water, saturated aqueous sodium bicarbonate and brine
  2. dry with materialdried over sodium sulfate
  3. filtrationThe sodium sulfate was filtered off
  4. concentrationthe filtrate was concentrated in vacuo
  5. customThe resultant residue was purified by preparative chromatography (Eluent: ethyl acetate/hexane=1/6)

Sources & evidence

ORD record
ord-f3c28fad64b04f218c9cb9e7ff996992
Source dataset
uspto-grants-2013_12
Patent number
US08604069B2

Reaction notes

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