反应详情

A suspension of 4-(6-chlorobenzo[d]thiazol-2-ylamino)benzoic acid (63A) (6.62 g, 21.72 mmol), EDC (4.37 g, 22.81 mmol) and HOBt (3.08 mg, 22.81 mmol) in a mixed solvent of DMF (25 mL) and CH2Cl2 (50 mL) was stirred for 5 min, and then 2-chloro-3-hydrazinylpyrazine (61A) (3.14 g, 21.72 mmol) and triethylamine (4.4 g, 43.4 mmol) were added. The mixture was stirred at room temperature over the weekend. Additional EDC (1.5 g, 7.85 mmol) and HOBt (1.15 g, 8.45 mmol) were added in and the reaction mixture stirred for another 2 h before concentrated in vacuo. The obtained residue was partitioned between EtOAc (250 mL) and water (200 mL), and the separated EtOAc layer washed with water (2×200 mL), and concentrated in vacuo. The crude product was triturated with water (50 mL) and EtOAc (20 mL) and isolated by filtration, rinsed with water and then air dried to yield the title compound as a dark brown solid (6.17 g). The second crop of the product was isolated from the concentrated mother liquor using the same trituration process (0.76 g) (total 6.93 g, 74% yield). HPLC/MS (Method C): retention time=2.43 min, [M+H]+=431.1. 1H NMR (500 MHz, DMSO-d6) δ 10.90 (s, 1H), 10.41 (s, 1H), 9.12 (s, 1H), 8.09 (d, J=2.20 Hz, 1H), 7.99 (d, J=2.20 Hz, 1H), 7.91-7.97 (m, 2H), 7.85-7.90 (m, 2H), 7.78 (d, J=2.75 Hz, 1H), 7.65 (d, J=8.80 Hz, 1H), 7.37 (dd, J=8.80, 2.20 Hz, 1H).

1. stirringThe mixture was stirred at room temperature over the weekend
2. stirringstirred for another 2 h
3. concentrationbefore concentrated in vacuo
4. customThe obtained residue was partitioned between EtOAc (250 mL) and water (200 mL)
5. washthe separated EtOAc layer washed with water (2×200 mL)
6. concentrationconcentrated in vacuo
7. customThe crude product was triturated with water (50 mL) and EtOAc (20 mL)
8. customisolated by filtration
9. washrinsed with water
10. customair dried