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

HRID 1912083Notes

Reaction equation

HRID 1912083 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]=[C:34]([CH3:36])[CH:33]=[CH:32][C:31]=1[NH2:37].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.C(=O)(O)[O-].[Na+]>O.C(N(CC)CC)C.CN(C=O)C>[Cl:29][C:30]1[CH:35]=[C:34]([CH3:36])[CH:33]=[CH:32][C:31]=1[NH:37][C:20]([CH2:19][CH:18]([C:5]1[C:4]([CH:1]2[CH2:2][CH2:3]2)=[C:8]([CH:9]2[CH2:10][CH:11]([CH2:13][C:14]([CH3:15])([CH3:17])[CH3:16])[CH2:12]2)[O:7][N:6]=1)[CH2:23][CH2:24][C:25]([O:27][CH3:28])=[O:26])=[O:21]

Participants

9

Reactant 5

HCID 120072-Chloro-p-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 71114721Methyl 5-(2-chloro-4-methylphenylcarbamoyl)-4-{4-cyclopropyl-5-[3-(2,2-dimethylpropyl)cyclobutyl]isoxazol-3-yl}valerate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

6-Methyl 3-[4-Cyclopropyl-5-[3-(2,2-dimethylpropyl)cyclobutyl]isoxazol-3-yl]adipate (100 mg), 2-chloro-4-methylphenylamine (0.0377 mL) and DMF (1 mL) were mixed. To the mixture were added triethylamine (0.0354 mL), HOBt.H2O (47 mg) and WSC.HCl (58.8 mg) at ice temperature. The mixture was stirred at RT overnight. 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, 1 N hydrochloric acid 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=1/8) to give the title compound (63.3 mg).

Workup

  1. extractionThe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with water, 1 N hydrochloric acid and brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationThe magnesium sulfate was filtered off
  5. concentrationthe filtrate was concentrated in vacuo
  6. customThe resultant residue was purified by preparative chromatography (Eluent: ethyl acetate/hexane=1/8)

Sources & evidence

ORD record
ord-ab9a4d10a5c94ceb96464ab9c4d4ff85
Source dataset
uspto-grants-2013_12
Patent number
US08604069B2

Reaction notes

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