Amlodipine → 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

HRID 11319

Reaktionsgleichung

Reaktionsgleichung von HRID 11319
[CH3:1][CH2:2][O:3][C:4]([C:6]1[CH:11]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:17]=2[Cl:18])[C:10]([C:19]([O:21][CH3:22])=[O:20])=[C:9]([CH3:23])[NH:8][C:7]=1[CH2:24][O:25][CH2:26][CH2:27][NH2:28])=[O:5].COC(C1C(C2C=CC=CC=2Cl)C(C(OC)=O)=C(C)NC=1COCCN[C:56](=[O:73])[CH2:57][O:58][C:59]1[CH:64]=[CH:63][C:62]([C:65]2[CH2:70][CH2:69][C:68](=[O:71])[NH:67][N:66]=2)=[CH:61][C:60]=1[Cl:72])=O>C(OCC)(=O)C>[CH3:22][O:21][C:19]([C:10]1[CH:11]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:17]=2[Cl:18])[C:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])=[C:7]([CH2:24][O:25][CH2:26][CH2:27][NH:28][C:56](=[O:73])[CH2:57][O:58][C:59]2[CH:64]=[CH:63][C:62]([C:65]3[CH2:70][CH2:69][C:68](=[O:71])[NH:67][N:66]=3)=[CH:61][C:60]=2[Cl:72])[NH:8][C:9]=1[CH3:23])=[O:20]

Komponenten

4

Edukt 2

HCID 2162AmlodipineHCID 10009561Ati-22-107

Produkt 1

HCID 104394822-(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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

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)

Quellen und Nachweise

ORD-Eintrag
ord-9e3c8905ad5848d0b462ca54136edada
Quelldatensatz
uspto-grants-2006_08
Patentnummer
US07098211B2

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