反应详情

To 6-(1,1-difluoro-butyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-c]pyridine (0.252 g, 1.05 mmol) and N,N-diisopropylethylamine (0.28 g, 2.2 mmol) in DCM (4.2 mL) cooled with an ice bath under nitrogen was added chloroacetyl chloride (0.09 g, 0.8 mmol), dropwise. After stirring at this temperature for 1.5 h, (2R,5R)-5-(hydroxy-thiazol-2-yl-methyl)-2-methyl-piperazine-1-carboxylic acid tert-butyl ester (0.18 g, 0.6 mmol) in DCM (0.5 mL) was added. The reaction was stirred at room temperature for 18 h, then saturated aqueous sodium bicarbonate was added and the mixture extracted with DCM (3×). The combined organic extracts were filtered and concentrated. Chromatography (silica gel, gradient elution, 0-100%, EtOAc in petrol 40-60) gave the title compound (0.076 g). MS: [M+H]+=594.

1. stirringThe reaction was stirred at room temperature for 18 h
2. extractionthe mixture extracted with DCM (3×)
3. filtrationThe combined organic extracts were filtered
4. concentrationconcentrated
5. washChromatography (silica gel, gradient elution, 0-100%, EtOAc in petrol 40-60)