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

HRID 1912056Notes

Reaction equation

HRID 1912056 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]=[CH:35][C:34]([CH3:37])=[CH:33][C:32]=1[NH2:38].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.C(=O)(O)[O-].[Na+]>O.CN(C=O)C>[Cl:30][C:31]1[CH:36]=[CH:35][C:34]([CH3:37])=[CH:33][C:32]=1[NH:38][C:27]([CH2:26][CH:17]([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]([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

8

Reactant 5

HCID 667702-Chloro-5-methylanilineHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 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 71135567tert-Butyl 4-(2-chloro-5-methylphenylcarbamoyl)-3-[4-cyclopropyl-5-(3-isobutylcyclobutyl)isoxazol-3-yl]butanoateYield 33.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Mono-tert-butyl 3-[4-cyclopropyl-5-(3-isobutylcyclobutyl)isoxazol-3-yl]glutarate (2.83 g) and DMF (28 mL) were mixed. After an addition of 2-chloro-5-methylphenylamine (1.184 g), HOBt.H2O (1.28 g) and WSC.HCl (1.60 g) to the resultant solution, the mixture was stirred at RT for 2 days. To the reaction mixture was added saturated aqueous sodium bicarbonate, 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 silica gel column chromatography (Eluent: ethyl acetate/hexane=1/15→1/10→1/8) to give the title compound (1.241 g).

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 silica gel column chromatography (Eluent: ethyl acetate/hexane=1/15→1/10→1/8)

Sources & evidence

ORD record
ord-22a2f0eeba114fb2b56ead414da3c983
Source dataset
uspto-grants-2013_12
Patent number
US08604069B2

Reaction notes

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