3,4-Dimethoxyaniline (4.70 g, 30.7 mmol) was used as starting material, which was dissolved in dichloromethane (50 ml), pyridine (8.0 ml, 3 eq.) was added, followed by slow dropwise addition of propionyl chloride (3.5 ml, 40.5 mmol). The reaction mixture was stirred at room temperature for 1 hour and 50 minutes. After completion of the reaction, the mixture was poured into a mixture consisting of water (200 ml) and concentrated hydrochloric acid (8 ml). The organic and aqueous phases were separated and the aqueous phase was extracted once with dichloromethane. The organic phases were combined, washed with brine, dried over magnesium sulfate, and concentrated to give 6.89 g of an oil which crystallized in a few minutes. Recrystallization by mixed solvent recrystallization from ethyl acetate and heptane gave 3.60 g (49% yield) of N-(3,4-dimethoxyphenyl)propanamide as dark colored crystals. The above obtained N-(3,4-dimethoxyphenyl)propanamide (2.1 g, 10.0 mmol) was mixed with DMF (1.1 ml, 15 mmol) and POCl3 (6.5 ml, 70 mmol) was added dropwise slowly at room temperature. After the dropwise addition, the reaction mixture was stirred at 75°C for 2 hours. After completion of the reaction, the mixture was poured into ice water (100 ml), stirred for 30 min and filtered. The solid was washed with toluene and acetonitrile to give 1.60 g (67% yield) of 2-chloro-6,7-dimethoxy-3-methylquinoline as a solid. The resulting 2-chloro-6,7-dimethoxy-3-methylquinoline was reacted with 1-cyclopropylpiperazine according to General Method (B) to afford the target compound.1H NMR (DMSO-d6) δ 0.83 (m, 2H), 1.23 (m, 2H), 2.42 (s, 3H), 2.94 (m, 1H), 3.40-4.50 (m, 8H), 3.88 (s, 3H), 3.91 (s, 3H), 7.29 (s, 1H), 7.48 (br s, 1H), 8.12 (br s, 1H), 11.24 (br s, 1H); HPLC-MS: m/z 328 (MH+); Rt = 1.63 min.
