反应详情

Diisopropylethylamine (0.19 ml, 1.12 mmol), EDC (0.098 g, 0.51 mmol) and HOAT (0.070 g, 0.51 mmol) were added to a stirred solution of 3,4-dichloro-5-methyl-1H-pyrrole-2-carboxylic acid (Intermediate 3, 0.1 g, 0.51 mmol) in DMF (1.5 ml) at room temperature. The resultant solution was stirred for 30 mins and 2-(4-aminopiperidin-1-yl)-1,3-thiazole-5-carboxamide hydrochloride (Intermediate 81; 0.163 g, 0.62 mmol) was added. The reaction was stirred at room temperature overnight under nitrogen. The reaction was stirred overnight, then concentrated under vacuum and the residue was partitioned between water and EtOAc. The aqueous layer was extracted with EtOAc and the combined organic extracts were washed with 1 N HCl, water and brine, dried over MgSO4 and concentrated under vacuum. The residue was purified by reverse phase chromatography (water/acetonitrile gradient, 20-95%) to give the desired product as a white solid (50 mg).

1. stirringThe reaction was stirred overnight
2. concentrationconcentrated under vacuum
3. customthe residue was partitioned between water and EtOAc
4. extractionThe aqueous layer was extracted with EtOAc
5. washthe combined organic extracts were washed with 1 N HCl, water and brine
6. dry with materialdried over MgSO4
7. concentrationconcentrated under vacuum
8. customThe residue was purified by reverse phase chromatography (water/acetonitrile gradient, 20-95%)