تفاعل #11415

معادلة التفاعل

amlodipine

Compound 8

2-(2-{2-[2-Chloro-4-(6-oxo-1,4,5,6-tetrahydro-pyridazin-3-yl)-phenoxy]-acetylamino}-ethoxymethyl)-4-(2-chloro-phenyl)-6-methyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid dimethyl ester

→

Compound 9

2-(2-{2-[2-Chloro-4-(6-oxo-1,4,5,6-tetrahydro-pyridazin-3-yl)-phenoxy]-acetylamino}-ethoxymethyl)-4-(2-chloro-phenyl)-6-methyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester

المذيبات

ethyl acetate

ظروف التفاعل

الإجراء التجريبي

2-(2-{2-[2-Chloro-4-(6-oxo-1,4,5,6-tetrahydro-pyridazin-3-yl)-phenoxy]-acetylamino}-ethoxymethyl)-4-(2-chloro-phenyl)-6-methyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester (Compound 9) (12b) was synthesized from commercial amlodipine (5b, 1.73 g, 4.23 mmol) and 6-{4-[3-carboxymethoxy]-3-chlorophenyl}-4,5-dihydro-3(2H)-pyridazinone (11) using the same procedure as for Compound 8. Pure Compound 9 was obtained by re-crystallization from ethyl acetate (1.45 g, 51% yield, 99% pure by 10 min. LCMS (UV @ 215 nm: retention time=6.86 min., peak area=99%, TOF-ES+ with 25 eV cone voltage: m/z=673.30 (100%) & 675.30 (30%)). 1H NMR: (CDCl3, TMS internal standard, δ in ppm): 8.50 (1H, s), 7.85 (1H, d, J=2.20 Hz), 7.59 (1H, dd, J1=8.60 Hz, J2=2.20 Hz), 7.38 (1H, dd, J1=7.78 Hz, J2=1.65 Hz), 7.23 (1H, dd, J1=7.87 Hz, J2=1.28 Hz), 7.17 (1H, broad s), 7.13 (2H, td, J1=7.43 Hz, J2=1.28 Hz), 7.04 (1H, J=7.57 Hz, J2=1.71 Hz), 6.94 (1H, d, J=8.78 Hz), 5.40 (1H, s), 4.76 (1H, d, J=15.83 Hz), 4.68 (1H, d, J=15.83 Hz), 4.62 (2H, s), 4.04 (2H, m, J1=7.12 Hz), 3.77–3.63 (4H, m), 3.62 (3H, s), 2.94 (2H, t, J=8.32 Hz), 2.61 (2H, t, J=8.23 Hz), 2.35 (3H, s), 1.18 (3H, t, J=7.14)

المصدر