Benzoyl Peroxide → N-(5-Bromo-thiazol-2-yl)-3-cyclohexyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide

HRID 1018823Notes

Reaction equation

HRID 1018823 reaction equation
[CH:1]1([CH2:7][C@H:8]([N:17]2[CH2:25][C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:18]2=[O:26])[C:9]([NH:11][C:12]2[S:13][CH:14]=[CH:15][N:16]=2)=[O:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Br:27]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[Br:27][C:14]1[S:13][C:12]([NH:11][C:9](=[O:10])[CH:8]([N:17]2[CH2:25][C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:18]2=[O:26])[CH2:7][CH:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)=[N:16][CH:15]=1

Participants

5

Reactant 3

HCID 7187Benzoyl Peroxide2×HCID 67184N-bromobutanimide2×HCID 9947513(S)-3-cyclohexyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-N-thiazol-2-yl-propionamide

Product 1

HCID 18402211N-(5-Bromo-thiazol-2-yl)-3-cyclohexyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamideYield 58%

Reagents, catalysts & solvents 1

HCID 5943Carbon TetrachlorideSolvent

Conditions

Temperature
95 °C

Procedure

To a suspension of (S)-3-cyclohexyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-N-thiazol-2-yl-propionamide (Prepared in Example 1; 21 mg; 0.06 mmol) and N-bromosuccinimide (11 mg; 0.06 mmol) in anhydrous carbon tetrachloride (1.0 mL) was added benzoyl peroxide (1 mg; 0.004 mmol). The mixture was stirred at 95° C. in a sealed tube. After 1.5 h, N-bromosuccinimide (2 mg) and benzoyl peroxide (1 mg) were added and the mixture stirred for 30 min. further. The mixture was allowed to cool to room temperature and the solvent removed in vacuo. The residue was taken up into ethyl acetate and washed with water. The organic extract was washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude residue was purified by flash chromatography (Biotage 12S, eluent: 20% ethyl acetate/hexanes to give 15 mg (58%) of N-(5-Bromo-thiazol-2-yl)-3-cyclohexyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide as a grey foam: EI-HRMS m/e calcd for C20H23BrN3O2S (M+) 447.0616, found 447.0623.

Workup

  1. stirringthe mixture stirred for 30 min. further
  2. temperatureto cool to room temperature
  3. customthe solvent removed in vacuo
  4. washwashed with water
  5. extractionThe organic extract
  6. washwas washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude residue was purified by flash chromatography (Biotage 12S, eluent

Sources & evidence

ORD record
ord-02c3e1bb262940ed84a596ce05583bdb
Source dataset
uspto-grants-2002_11
Patent number
US06482951B2

Reaction notes

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