Chloroacetaldehyde → [3-(2-Methoxy-1-methyl-ethoxy)-5-phenoxy-pyridine-2-yl]-thiazole-2-yl-amine

Participants

Reaction Conditions

Reaction Steps

[3-(2-Methoxy-1-methyl-ethoxy)-5-phenoxy-pyridin-2-yl]-thiourea (0.2 mmol) is dissolved in DMF (1 ml) and chloro-acetaldehyde (1.0 eq., 55% in water) is added and stirred three hours at 100° 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-1-methyl-ethoxy)-5-phenoxy-pyridine-2-yl]-thiazole-2-yl-amine (“A28”) is obtained after reversed phase column chromatography (acetonitrile/water+0.1% TFA) as yellow solid in a yield of 46%. HPLC (method C): 1.80 min; LC-MS (method A): 1.72 min, 358.15 (MH+); 1H-NMR (DMSO-d6, 500 MHz): δ [ppm] 7.739 (d, 1H, J=2.3 Hz), 7.477 (d, 1H, J=3.9 Hz), 7.421-7.369 (m, 3H), 7.142-7.087 (m, 2H), 7.025 (d, 2H, J=8 Hz), 5.408 (br, 1H), 4.737-4.696 (m, 1H), 3.639 (dd, 1H, J=6.5 Hz, J=10.6 Hz), 3.505 (dd, 1H, J=3.6 Hz, J=10.6 Hz), 3.3 (S, 3H), 1.268 (D, 3H, J=6.4 Hz).

Provenance & Evidence