ChemicalBook CAS DataBase List Pimobendan

Pimobendan synthesis

11synthesis methods

Product Name:Pimobendan
CAS Number:74150-27-9
Molecular formula:C19H18N4O2
Molecular Weight:334.37

123-11-5 Synthesis

123-11-5
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6-(3,4-diaminophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one

74150-02-0
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74150-27-9
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Yield:74150-27-9 93.8%

Reaction Conditions:

with sodium metabisulfite in N,N-dimethyl-formamide at 110 - 115; for 1.5 h;Product distribution / selectivity;

Steps:

4.4.A.1

A reactor was charged with 6-(3,4-diaminophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one (II, 1 .0 eq.), prepared according to example 3, and sodium metabisulfite (1.1 eq.) in DMF (3.5 L/kg; V:m₍n₎). The mixture was heated to 1 10 - 1 15 °C and 4-Methoxybenzaldehyde (1 .0 eq.) was added over 30 min with stirring. After the addition was complete stirring was continued for a further 60 min. The suspension was cooled to 60 - 70 °C, filtered and the filter cake was washed with DMF (1 .24 L/kg; V:m₍n₎). The clear filtrate was treated with aq. ammonia at 45 - 55 °C to adjust the pH to a value of 8 - 9. The mixture was then cooled to 25 - 30 °C and water (6.87 L/kg; V:m₍n₎) was added slowly with stirring. Stirring was continued for a further 1 - 2 h at room temperature and the precipitated product was separated by filtration. The solid was washed with water (4 x 1.24 L/kg; V:m₍n₎) and acetone (4 x 2.47 L/kg; V:m₍n₎) and dried under reduced pressure at 40 - 60 °C to obtain 93.8 % of crystalline 6-(2-(4-methoxyphenyl)- 1 H-benzo[d]imidazol-5-yl)-5-methyl-4,5-dihydro-pyrida-zin-3(2H)-one monohydrate. Residual solvents: H₂0, 4.97 % (KF). HPLC: 99.04 %. Mp: 162-164 °C. ¹H-NMR (DMSO, 300 MHz): δ = 12.82 (s, br. 1 H, NH), 10.89 (s, 1 H, NH), 8.14 - 8.1 1 (d, 2 H, 2 x CH, arom), 7.93 (s, 1 H, arom), 7.71 -7.68 (1 H, d, arom.), 7.59 - 7.56 (1 d, H, arom.), 7.13 - 7.10 (d, 2 H, arom.), 3.83 (s, 3 H, CH₃0), 3.53 - 3.44 (m, 1 H, CH), 3.56 (s, br), 2.87-2.68 (dd, 1 H, CH₂), 2.28 - 2.22 (dd, 1 H, CH₂), 1.13 - 1 .1 1 (d, 3 H, CH₃). C-NMR (DMSO, 75 MHz): δ = 166.23, 160.76, 153.31 , 152.58, 128.78, 128.09, 122.37, 1 19.98, 1 14.37, 55.30, 33.65, 27.45, 16.02. IR (KBr, cm^"1): 3273, 1620, 1493, 1459, 1422, 1393, 1380, 1342, 1297, 1252, 1 179, 1079, 1034, 960, 924, 893, 833, 813, 773, 744, 687, 639, 608, 519.