反应详情

温度

80 °C

To a mixture of 5-chloro-4-[4-(5-methyl-isoxazol-3-ylmethyl)-piperazin-1-yl]-3-nitro-pyridin-2-ylamine (0.031 g, 0.09 mmol) and EtOH (3.0 ml) was added 4-morpholin-4-ylmethyl-benzaldehyde (0.025 g, 0.12 mmol) followed by a freshly prepared aqueous solution of Na2S2O4 (1M; 0.36 ml, 0.36 mmol). The reaction mixture was stirred at 80° C. for 20 h, then allowed to cool to room temperature and concentrated in vacuo. The resulting residue was absorbed on silica, and the free-running powder was placed on a 10 g isolute silica column. Elution with a gradient of methanol (0 to 7%) in ethyl acetate/dichloromethane (v:v; 1:1) afforded a yellow solid. The title compound was obtained as a yellow solid after trituration with diethyl ether (0.018 g, 39%); 1H-NMR (500 MHz, DMSO-d6) 2.38 (br s, 4H) and 3.58 (t, J=4.8 Hz, 4H) (morpholine N(CH2)2 and morpholine O(CH2)2), 2.40 (s, 3H, isoxazole 5-CH3), 2.63 (br s, 4H, piperazine N(CH2)2), 3.53 (s, 2H) and 3.60 (s, 2H) (C6H4CH2N and NCH2 isoxazole), 3.70 (br s, 4H, piperazine N(CH2)2), 6.25 (s, 1H, isoxazole 4-H), 7.47 (d, J=8.2 Hz, 2H) and 8.13 (d, J=8.2 Hz, 2H) (3,5-C6H4— and 2,6-C6H4—), 8.11 (s, 1H, imidazo[4,5-b]pyridine 5-H), 13.48 (br s, 1H, imidazo[4,5-b]pyridine N—H);

1. temperatureto cool to room temperature
2. concentrationconcentrated in vacuo
3. customThe resulting residue was absorbed on silica
4. washElution with a gradient of methanol (0 to 7%) in ethyl acetate/dichloromethane (v:v; 1:1)
5. customafforded a yellow solid