Chloroacetaldehyde → [3-(2-Methoxy-ethoxy)-5-(pyridine-3-yloxy)pyridine-2-yl]-thiazole-2-yl-amine

Participants

Reaction Conditions

Reaction Steps

[3-(2-Methoxy-ethoxy)-5-(pyridine-3-yloxy)-pyridine-2-yl]-thiourea (0.34 mmol) is dissolved in DMF (1.2 ml) and chloro-acetaldehyde (1.0 eq., 55% in water) is added and stirred 90 minutes at 120° C. After cooling to room temperature the suspension is pored into ice-water and extracted with methyl-tert.-butyl ether. The combined organic phases are washed with brine and dried over MgSO4. The solvent is removed in vacuo. [3-(2-Methoxy-ethoxy)-5-(pyridine-3-yloxy)pyridine-2-yl]-thiazole-2-yl-amine (“A31”) is obtained after reversed phase column chromatography (acetonitrile/water+0.1% TFA) as yellow solid in a yield of 37%. HPLC (method C): 1.17 min; LC-MS (method A): 1.07 min, 345.15 (MH+); 1H-NMR (DMSO-d6, 500 MHz): δ [ppm] 10.403 (s, 1H), 8.477 (d, 1H, J=2.7 Hz), 8.398 (dd, 1H, J=1.3 Hz, J=4.6 Hz), 7.832 (d, 1H, J=2.3 Hz), 7.558-7.533 (m, 1H), 7.500-7.475 (m, 2H), 7.456 (d, 1H, J=2.3 Hz), 7.116 (d, 1H, J=3.7 Hz), 4.279 (t, 2H, J=4.6 Hz), 3.771 (t, 2H, J=4.6 Hz), 3.339 (s, 3H).

Provenance & Evidence