Ethyl 5-phenylthiazole-2-carboxylate → (S)-Methyl 3-methyl-2-(1-oxo-6-(4-(5-phenylthiazole-2-carboxamido)phenyl)isoindolin-2-yl)butanoate

HRID 404087Notes

Reaction equation

HRID 404087 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:16]=[C:15]3[C:11]([CH2:12][N:13]([C@@H:18]([CH:23]([CH3:25])[CH3:24])[C:19]([O:21][CH3:22])=[O:20])[C:14]3=[O:17])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[C:26]1([C:32]2[S:36][C:35]([C:37](OCC)=[O:38])=[N:34][CH:33]=2)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C[Al](C)C>C1(C)C=CC=CC=1>[CH3:24][CH:23]([CH3:25])[C@H:18]([N:13]1[CH2:12][C:11]2[C:15](=[CH:16][C:8]([C:5]3[CH:4]=[CH:3][C:2]([NH:1][C:37]([C:35]4[S:36][C:32]([C:26]5[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=5)=[CH:33][N:34]=4)=[O:38])=[CH:7][CH:6]=3)=[CH:9][CH:10]=2)[C:14]1=[O:17])[C:19]([O:21][CH3:22])=[O:20]

Participants

5

Reactant 3

HCID 12830686Ethyl 5-phenylthiazole-2-carboxylateHCID 16682925TrimethylaluminumHCID 131731441(S)-Methyl 2-(6-(4-aminophenyl)-1-oxoisoindolin-2-yl)-3-methylbutanoate

Product 1

HCID 123332092(S)-Methyl 3-methyl-2-(1-oxo-6-(4-(5-phenylthiazole-2-carboxamido)phenyl)isoindolin-2-yl)butanoateYield 29%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of the compound of example 6 (405 mg, 1.2 mmol) and ethyl 5-phenylthiazole-2-carboxylate (233 mg, 1 mmol) in toluene (15 mL) in a sealed tube, was added 2M solution of AlMe3 (135 mg, 1.875 mmol) and the reaction mixture was heated at 80° C. for 2 h. After completion of the reaction, the reaction mixture was cooled to room temperature and quenched with saturated ammonium chloride. The resulting solution was extracted with ethyl acetate. The ethyl acetate extract was washed with water, brine, dried over anhydrous sodium sulphate and concentrated to obtain a crude material, which was purified using column chromatography (30% ethyl acetate in petroleum ether) to afford the title compound.

Workup

  1. customAfter completion of the reaction
  2. temperaturethe reaction mixture was cooled to room temperature
  3. customquenched with saturated ammonium chloride
  4. extractionThe resulting solution was extracted with ethyl acetate
  5. extractionThe ethyl acetate extract
  6. washwas washed with water, brine
  7. dry with materialdried over anhydrous sodium sulphate
  8. concentrationconcentrated
  9. customto obtain a crude material, which
  10. customwas purified

Sources & evidence

ORD record
ord-47294878b9a44157bda3f11ae5d882a4
Source dataset
uspto-grants-2014_06
Patent number
US08748426B2

Reaction notes

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