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

HRID 1912058Notes

Reaction equation

HRID 1912058 reaction equation
[CH:1]1([C:4]2[C:5]([CH:17]([CH2:26][C:27]([O-:29])=O)[CH2:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[N:6][O:7][C:8]=2[CH:9]2[CH2:12][CH:11]([CH2:13][CH:14]([CH3:16])[CH3:15])[CH2:10]2)[CH2:3][CH2:2]1.[Cl:30][C:31]1[CH:36]=[C:35]([CH3:37])[CH:34]=[CH:33][C:32]=1[NH2:38].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>O.CN(C=O)C>[Cl:30][C:31]1[CH:36]=[C:35]([CH3:37])[CH:34]=[CH:33][C:32]=1[NH:38][C:27]([CH2:26][CH:17]([C:5]1[C:4]([CH:1]2[CH2:3][CH2:2]2)=[C:8]([CH:9]2[CH2:10][CH:11]([CH2:13][CH:14]([CH3:16])[CH3:15])[CH2:12]2)[O:7][N:6]=1)[CH2:18][C:19]([O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:20])=[O:29]

Participants

7

Reactant 4

HCID 120072-Chloro-p-toluidineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86675036Mono-tert-butyl 3-[4-cyclopropyl-5-(3-isobutylcyclobutyl)isoxazol-3-yl]glutarate

Product 1

HCID 71134796tert-Butyl 4-(2-chloro-4-methylphenylcarbamoyl)-3-[4-cyclopropyl-5-(3-isobutylcyclobutyl)isoxazol-3-yl]butanoateYield 52.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Procedure

Mono-tert-butyl 3-[4-cyclopropyl-5-(3-isobutylcyclobutyl)isoxazol-3-yl]glutarate (245 mg) and DMF (2 mL) were mixed. After an addition of 2-chloro-4-methylphenylamine (67 mg), HOBt.H2O (87 mg) and WSC.HCl (108 mg) to the mixture, the reaction mixture was stirred at RT. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate, water 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=1/4) to give the title compound (131 mg).

Workup

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

Sources & evidence

ORD record
ord-e0184b1a0aad45fdbe4478ee6e2381e5
Source dataset
uspto-grants-2013_12
Patent number
US08604069B2

Reaction notes

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