Diisopropylcarbodiimide → (S)-2-(3,5-dimethylphenylacetamido)-3-(4-methylphenyl)-N-[4-(imidazo[2,1-b]benzothiazol-2-yl]phenyl]propanamide

Beteiligte Stoffe

Reaktionsschritte

HATU (258 mg, 0.68 mmol) and DIPEA (197 μl, 1.13 mmol) were added to a solution of 4-[(imidazo[2,1-b]benzothiazol-2-yl)]aniline (150 mg, 0.56 mmol) and N-Boc-4-methylphenylalanine (158 mg, 0.56 mmol) in dry THF (11 ml). After 48 h at room temperature the solvent was removed under reduced pressure and the crude mixture was purified by flash chromatography (DCM containing 1% MeOH) to afford the desired N-Boc derivative that was dissolved in dry DCM (5 ml). TFA (5 ml) was then added and the reaction mixture was stirred at room temperature for 4 hours. Then the solvent was removed under reduced pressure and the crude mixture was purified by flash chromatography (DCM containing 10% EtOH) to afford 2-amino-3-(4-methylphenyl)-N-[4-(imidazo[2,1-b]benzothiazol-2-yl)phenyl]-propanamide in nearly quantitative yield. A suspension of 2-amino-3-(4-methylphenyl)-N-[4-(imidazo[2,1-b]benzothiazol-2-yl]phenyl]propanamide (150 mg, 0.35 mmol) in dry DCM (4 ml) was then mixed to 3,5-dimethylphenylacetic acid (60.6 mg, 0.37 mmol) and DMAP (21.5 mg, 0.17 mmol). Once the solution was obtained, DIC (83 l, 0.53 mmol) was added. After 4.5 h at room temperature the solvent was removed under reduced pressure and the crude mixture was purified by flash chromatography (DCM containing 2% EtOH) to afford (S)-2-(3,5-dimethylphenylacetamido)-3-(4-methylphenyl)-N-[4-(imidazo[2,1-b]benzothiazol-2-yl]phenyl]propanamide that was further on purified by crystallization in CHCl3 (32% c.y.)

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