ChemInform Abstract: SYNTH. VON PYRIDAZIN‐HYDRAZINEN MIT HYPOTENSIVER WIRKUNG 2. MITT.

Abstract

Das Dichlor‐pyridazin (II) reagiert mit sekundären Aminen zu den Amino‐pyridazinen (III), mit Morpholin zum Bis‐morpholino‐pyridazin (I).

Antihypertensives. N-1H-Pyrrol-1-yl-3-pyridazinamines

“…6-Chloro-3-[4-(2-methoxy phenyl)-1piperazinyl]pyridazine (II-7). A mixture of 3,6-dichloropyridazine (14.9 g, 0.1 mol) and l-(2-methoxyphenyl)piperazine (36 g, 0.2 mol) in C2H6OH (200 mL) was refluxed for 10 h. After evaporation of the solvent, the residue was triturated with H20, and the insolube material was filtered and crystallized from EtOAc: yield 21.5 g; NMR (Me2SO-d6) 8 3.08 (t, 4 H, «/Ch2ch2 = 5.5 Hz, CH2NC6H3) 3.74 (t, 4 H, CH2N), 3.81 (s, 3 H, Cti30), 6.9-7.2 (m, 4 H, phenyl protons), 7.48 (d, 1 H, -JH4-h5 = 10 Hz, H5), 7.61 (d, 1 H, H4).…”

“…3.90 (t, 4 H, CH20), 6.27 (d, 2 H, JH^h3 = 2.5 Hz, pyrrol H3), 6.32 (d, 1 H, JH4-H5 = 10 Hz, H4), 6.85 (d, 2 H, pyrrol H2), 6.90 (d, 1 H, H5), 7.65 (s, 1 , NH). IV-(2,5-Dimethyl-Iff -pyrrol-1-yl)-IV-methyl-6-(4morpholinyl)-3-pyridazinamine (VI-39), (a) 80% NaH in mineral oil (6.3 g, 0.21 mol) was added to a solution of VI-30 (31 g, 0.1 mol) in anhydrous DMF (250 mL).…”

“…N -(2,5-Dimethyl-Iffpyrrol-1-yl)-2-methyl-6-(4morpholinyl)-3(2ff)-pyridazinimine (IX). The combined hexane liquors of the previous preparation (a) were evaporated to dryness, and the residue was chromatographed on silica gel [500 g, mobil phase hexane-Et20 (1:1)]: yield 2.2 g; mp [162][163] °C (from hexane); NMR (CDC13) 2.01 (s, 6 H, CH3C=), 3.22 (t, 4 H, JCh2ch2 = 6.5 Hz, CH2N), 3.78 (s, 3 H, CH3N), 3.83 (t, 4 H, CH20), 5.81 (s, 2 H, pyrrol CH=C), 6.28 (d, 1 H, =7ch-ch = 10 Hz, H4), 6.78 (d, 1 H, H5).…”

“…The compound obtained by chromatography, as described in the previous preparation, was crystallized from EtOH: yield I. 5 g; mp 153-155 °C; NMR (for the attributions, see Scheme II) (CDClg) 2.94 (ddd, 2 H, Jchj-Hc = 0.5 Hz, J 2-2 = 3 Hz, Jch^hs = 2.5 Hz, =CCH2C), 3.50 (t, 4 H, Jch2ch2 = 5 Hz, CH2N), 3.85 (t, 4 H, CH20), 4.87 (ddt, 1 H, J 3-6 = 2.5 Hz, t/ ,-, = 8 Hz, H^), 6.78 (dt, 1 H, Ha),6.99 (d, 1 H, Jh4-h5 =10 Hz, H5) 7.61 (d, 1 H, H4), 7.66 (dt, 1 H, Hc). Anal.…”