反应详情

To a solution of 3-tert-butoxycarbonyl-7-chloro-6-mercaptomethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.202 g, 0.617 mmol) and N-(5-bromothiazol-2-yl)-cyclopropylmethylamine (0.14 g, 0.62 mmol) in anhydrous DMF (6.2 mL) at room temperature add cesium carbonate (0.22 g, 0.68 mmol). Stir at room temperature overnight and partition the reaction mixture between saturated aqueous NaHCO3 (50 mL) and DCM (100 mL). Dry the organic extract over Na2SO4, filter and concentrate in vacuo. Dissolve the residue in DCM, load the solution on to an Analogix® column (40 g) and purify the crude intermediate by preparative liquid chromatography (100:0 to 75:25 hexane/EtOAc over 30 min; 75:25 to 50:50 hexane/EtOAc over 33 min; 35 mL/min) to afford 3-tert-butoxycarbonyl-7-chloro-6-[2-(cyclopropylmethyl-amino)-thiazol-5-ylthiomethyl]-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.129 g, 44%). MS (ES+) m/z: 480.2 (M+H)+.

1. custompartition the reaction mixture between saturated aqueous NaHCO3 (50 mL) and DCM (100 mL)
2. customDry the
3. extractionorganic extract over Na2SO4
4. filtrationfilter
5. concentrationconcentrate in vacuo
6. dissolutionDissolve the residue in DCM
7. customload the solution on to an Analogix® column (40 g) and purify the crude intermediate by preparative liquid chromatography (100:0 to 75:25 hexane/EtOAc over 30 min; 75:25 to 50:50 hexane/EtOAc over 33 min; 35 mL/min)