2,3-Dichloropyrazine → (3-Chloropyrazin-2-yl)(2-phenylquinolin-7-yl)methanamine

Participants

Reaction Conditions

Reaction Steps

Benzhydryl-[1-(2-phenyl-quinolin-7-yl)-meth-(E)-ylidene]-amine (12.50 g, 31.4 mmol) was added to a 500 mL rbf fitted with a thermocouple. The flask was degassed and filled with nitrogen. THF (150 mL) was added and the solid dissolved. The mixture was cooled to −5° C. and 1.0 M of HMDS sodium salt in THF (39.2 mL) was added within 5 min. The temperature increased slightly to −3° C. The blue solution was stirred for 20 min at 0° C. and then 2,3-dichloropyrazine (5.61 g, 37.6 mmol) in THF (10 ml) was added within 3 min. The mixture was stirred for 30 min and then quenched with saturated NH4Cl/water (200 mL). EtOAc (200 mL) was added and the aqueous phase was removed. Toluene can also be used. The organic layer was washed with water (200 mL×2) and brine (200 mL). Concentrated HCl (10 mL) and water (200 mL) were added. The phases were separated and the organic layer was extracted with 0.1 M HCl (30 mL). The aqueous was washed with EtOAc (2×) and then saturated K2CO3 was used to adjust to pH 10. The aqueous solution was extracted with EtOAc (2×) and the combined organics were dried over Na2SO4, filtered, and concentrated in vacuo to a brown oil which solidified upon standing to yield the title compound as a brown solid (9.94 g, 81% yield). 1H NMR (400 MHz, CDCl3) δ ppm 2.30 (br s, 2H), 5.79 (s, 1H), 7.43-7.56 (m, 3H), 7.62 (dd, J=8.46, 1.89 Hz, 1H), 7.81 (d, J=8.34 Hz, 1H), 7.86 (d, J=8.59 Hz, 1H), 8.07 (d, J=1.01 Hz, 1H), 8.10-8.16 (m, 2H), 8.19 (d, J=8.59 Hz, 1H), 8.31 (d, J=2.27 Hz, 1H), 8.60 (d, J=2.53 Hz, 1H). MS (ES+): m/z=347.01/349.03 (100/68) [MH+].

Provenance & Evidence