4-Chloro-2-toluidine → Methyl 5-(4-chloro-2-methylphenylcarbamoyl)-4-{4-cyclopropyl-5-[3-(2,2-dimethylpropyl)cyclobutyl]isoxazol-3-yl}valerate

HRID 1912081Notes

Reaction equation

HRID 1912081 reaction equation
[CH:1]1([C:4]2[C:5]([CH:18]([CH2:23][CH2:24][C:25]([O:27][CH3:28])=[O:26])[CH2:19][C:20]([O-])=[O:21])=[N:6][O:7][C:8]=2[CH:9]2[CH2:12][CH:11]([CH2:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH2:10]2)[CH2:3][CH2:2]1.[Cl:29][C:30]1[CH:35]=[CH:34][C:33]([NH2:36])=[C:32]([CH3:37])[CH:31]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.C(=O)(O)[O-].[Na+]>O.CN(C=O)C>[Cl:29][C:30]1[CH:35]=[CH:34][C:33]([NH:36][C:20]([CH2:19][CH:18]([C:5]2[C:4]([CH:1]3[CH2:3][CH2:2]3)=[C:8]([CH:9]3[CH2:12][CH:11]([CH2:13][C:14]([CH3:17])([CH3:15])[CH3:16])[CH2:10]3)[O:7][N:6]=2)[CH2:23][CH2:24][C:25]([O:27][CH3:28])=[O:26])=[O:21])=[C:32]([CH3:37])[CH:31]=1

Participants

8

Reactant 5

HCID 72514-Chloro-2-toluidineHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 866750456-Methyl 3-[4-Cyclopropyl-5-[3-(2,2-dimethylpropyl)cyclobutyl]isoxazol-3-yl]adipate

Product 1

HCID 71114755Methyl 5-(4-chloro-2-methylphenylcarbamoyl)-4-{4-cyclopropyl-5-[3-(2,2-dimethylpropyl)cyclobutyl]isoxazol-3-yl}valerateYield 55.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

6-Methyl 3-{4-cyclopropyl-5-[3-(2,2-dimethylpropyl)cyclobutyl]isoxazol-3-yl}adipate (100 mg), 4-chloro-2-methylphenylamine (43.5 mg) and DMF (1 mL) were mixed. To the mixture were added HOBt.H2O (47 mg) and WSC.HCl (58.8 mg) at ice temperature. The mixture was stirred at RT, and further stirred at 70° C. To the reaction mixture was added saturated aqueous sodium bicarbonate at ice temperature. The mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, then dried over magnesium sulfate. The magnesium sulfate was filtered off and the filtrate was concentrated in vacuo. The resultant residue was purified by preparative chromatography (Eluent: ethyl acetate/hexane=1/4) to give the title compound (72.8 mg).

Workup

  1. stirringfurther stirred at 70° C
  2. extractionThe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationThe magnesium sulfate was filtered off
  6. concentrationthe filtrate was concentrated in vacuo
  7. customThe resultant residue was purified by preparative chromatography (Eluent: ethyl acetate/hexane=1/4)

Sources & evidence

ORD record
ord-831a49d868c0430fadbeb33b70446c17
Source dataset
uspto-grants-2013_12
Patent number
US08604069B2

Reaction notes

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