Preparation method of vilazodone or hydrochloride thereof
A technology of vilazodone and vilazodone hydrochloride, which is applied in the field of pharmaceutical and chemical industry, can solve problems such as being unsuitable for industrial production and application, complicated and tedious operation, etc., and achieve the effects of great practical application value, avoiding environmental pollution and reducing cost.
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Embodiment 1
[0042] Add compound (I) (35.0g), compound (II) (43.3g) in N-methylpyrrolidone (220ml), then add N,N-diisopropylethylamine (60.7g), sodium iodide (11.9g), heated to 95-105° C. for 18-20 hours, and TLC detected that the reaction was complete. Cool, add ethyl acetate (1.5L) and water (1.5L), stir for 10-15 minutes, separate layers, extract the water layer with ethyl acetate (1.5L), combine the organic layers, and saturated aqueous sodium chloride (1.5 L) washed, dried, filtered, and the filtrate was concentrated to dryness to obtain a yellow-brown oil.
[0043] Add acetone (350ml) to the oil to dissolve, add concentrated hydrochloric acid dropwise to pH 2-3, stir for 0.5 hours, filter, and wash the filter cake successively with ethyl acetate (350ml) and acetone (350ml). Air-dried at 35-45°C for 14-16 hours to obtain Compound A (50.6 g, off-white solid), with a mass yield of 144.6%.
Embodiment 2
[0045] Put N-methylpyrrolidone (1000ml) and compound A (50.0g) into the reaction flask, stir for 10-15 minutes, slowly add ammonia water (750ml), and stir for 42-47 hours. Purified water (2000ml) was slowly added to the reaction solution, stirred for 1-2 hours, filtered, the solid was washed with a small amount of water, and vacuum-dried for 18-20 hours to obtain Compound B (40.5g), an off-white solid, with a mass yield of 81.0%. The molar yield is 93.0%. As detected by HPLC, the purity was 98.82%.
Embodiment 3
[0047]Put compound B (40.0g) and tetrahydrofuran (2L) into the reaction flask, stir to dissolve, add activated carbon (4.0g), stir for 30-45 minutes; filter, add 1N hydrochloric acid solution (90.6ml) dropwise to the filtrate and stir for 30- 45 minutes. After filtering, washing with a small amount of tetrahydrofuran, the obtained solid was poured into purified water (1 L), and stirred for 24 hours. Filtration, vacuum drying at 40-45°C for 24-26 hours to obtain vilazodone hydrochloride, 39.5 g of white solid, mass yield 98.7%. Through HPLC detection, the product purity is 99.83%, the maximum mono-impurity is 0.02%, and the residual tetrahydrofuran is 36ppm.
[0048] MS-ESI(m / z): 442.22[M+H] +
[0049] 1 H-NMR (DMSO-d 6 ): δ1.70-1.74(m, 2H), 1.84(br, 2H), 2.78(t, 2H), 3.18-3.24(m, 6H), 3.55(br, 2H), 3.73(br, 2H), 7.21-7.23(d, 1H), 7.27(s, 1H), 7.41-7.43(s+d, 2H), 7.49(s, 1H), 7.53-7.55(d+s, 2H), 7.65(br, 1H , disappeared after heavy water exchange), 8.12 (s+br, 2H, one p...
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