反应详情

A suspension of 4-(thiazol-2-ylamino)benzoic acid (44A) (3.27 g, 14.7 mmol), EDC (2.85 g, 14.9 mmol) and HOBt (2.02 g, 14.9 mmol) in a mixed solvent of DMF (40 mL) and CH2Cl2 (80 mL) was stirred for 5 min, and then to this mixture was added in ethyl 2-hydrazinylnicotinate (4A) (2.7 g, 14.9 mmol) and triethylamine (2.25 g, 22.35 mmol). The mixture was stirred at room temperature for 3.5 h. Analysis by LC/MS indicated the starting material was not consumed. Additional amount of EDC (250 mg, 1.3 mmol) and ethyl 2-hydrazinylnicotinate (4A) (200 mg, 1.1 mmol) were added and the reaction mixture stirred overnight. The reaction mixture was concentrated in vacuo to one third of the initial volume, and then diluted with water (200 mL) and ethyl acetate (100 mL). The insoluble material was isolated by filtration to yield the title compound as a light brown solid (1.14 g). The filtrate was separated into organic and aqueous layers. The organic layer was washed with water, and then concentrated in vacuo. The obtained residue was triturated with methanol to yield the second crop of the title compound (1.35 g). (total 2.49 g, 44% yield). HPLC/MS (Method C): retention time=1.11 min, [M+H]+=384.2.

1. stirringThe mixture was stirred at room temperature for 3.5 h
2. customwas not consumed
3. stirringthe reaction mixture stirred overnight
4. concentrationThe reaction mixture was concentrated in vacuo to one third of the initial volume
5. additiondiluted with water (200 mL) and ethyl acetate (100 mL)
6. customThe insoluble material was isolated by filtration