OlMesartan MedoxoMil Ethyl Methyl Analog synthesis

Yield:-

Reaction Conditions:

with water;acetic acid at 50; for 4 h;

Steps:

6

(5-Methyl-2-oxo- 1 ,3-dioxol-4-ylmethyl) 4-( 1 -hydroxy- 1 -methylpropyl)-2-propyl- 1 -[2 '-( 1H- tetrazol-5-yl)biphenyl-4-yl-methyl]imidazole-5-carboxylate of formula VI (5-Methyl-2-oxo- 1 ,3-dioxol-4-yl)methyl 4-( 1 -hydroxy- 1 -methylpropyl)-2-propyl- 1 -((2'-( 1 - trityl-lH-tetrazol-5-yl)biphenyl-4-yl)methyl)-lH-imidazole-5-carboxylate of formula 6; 2,1 g were dissolved in acetic acid (10 ml) and after addition of water (5 ml) the mixture was heated to 50 °C for 4 h. After aspiration of trityl alcohol, evaporation and concentration crystallization from ethyl acetate was performed. 1.14 g of the product were obtained in the form of a white, crystalline substance with the content of 94.4% by weight as determined using the HPLC method in accordance with Example 1. NMR spectrum (CDC1₃): 0.85 t, 3 H, J= 7.5; 0.90 t, 3 H, J= 7.4; 1,55 s, 3 H; 1.65-1.70 m, 2 H; 1.80-1.90 m, 1 H; 1.95-2.05 m, 1 H; 2.20 s, 3 H; 2.55 t, 2 H, J = 7.5; 4.95 s, 2 H; 5.35 d, 1 H, J = 17.1 ; 5.45 d, 1 H, J = 17.1 ; 6.80 d, 2 H, J = 8.2; 7.10 d, 2 H, J= 8.2; 7.45 t, 1 H, J = 6.9; 7.50-7.55 m, 1 H; 7.55-7.60 m, 1 H; 7.80 d, 1 H, J = 7.7 ¹³C NMR spectrum (CDC1₃) 5.53, 9.41, 13.75, 21.17, 26.31, 29.10, 34.55, 49.10, 50.16, 53.84, 62.66, 73.41, 116.57, 122.79, 125.24, 128.24, 129.51, 130.71, 131.01, 131.37, 133.22, 135.25, 136.48, 138.72, 140.56, 140.91, 152.49, 152.88, 154.99, 160.26, 160.74.HR-MS: pro C₃₀H₃₃N₆O₆ [M+H]⁺, calculated 573.2456 m/z, found 573.2456 m/z.

References:

WO2012/69025,2012,A1 Location in patent:Page/Page column 12