e.g. Filippa Pettersson or Cancer Res. 75(6) , 1102-12, (2015) or 10.1002/anie.201600521

6??(substituted phenyl)??5??methyl??4, 5??dihydro??pyridazin??3 (2H)??ones of medicinal interest. The synthesis of SK&F 94836 and SK&F 95654

…, J Mistry, MB Mitchell, KD Pancholi…

Index: Burpitt; Crawford; Davies; Mistry; Mitchell; Pancholi; Coates Journal of Heterocyclic Chemistry, 1988 , vol. 25, # 6 p. 1689 - 1695

Full Text: HTML

Citation Number: 14

Abstract

Abstract Two synthetic routes to the dihydropyridazinone-cyanoguanidine 4 (SK&F 94836) are described, both proceeding via the anilino compound 6. An efficient synthesis of the dihydropyridazinone-pyridone 5 (SK&F 95654) is reported. This synthesis proceeds via the fluoro-keto-acid 24, with subsequent displacement of the fluoro substituent by 4-pyridone. The surprising effectiveness of water as a solvent in this reaction has been highlighted.

Acetanilide Structure

~%

4-(4-Aminophenyl)-3-methyl-4-oxobutanoic acid hydrochloride Structure

4-(4-Aminopheny...

DIETHYL 2-(1-(4-ACETAMIDOPHENYL)-1-OXOPROPAN-2-YL)MALONATE Structure

DIETHYL 2-(1-(4...

~%

4-(4-Aminophenyl)-3-methyl-4-oxobutanoic acid hydrochloride Structure

4-(4-Aminopheny...

N-[4-(2-chloropropanoyl)phenyl]acetamide Structure

N-[4-(2-chlorop...

~%

4-(4-Aminophenyl)-3-methyl-4-oxobutanoic acid hydrochloride Structure

4-(4-Aminopheny...

6-(4-acetamidophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one Structure

6-(4-acetamidop...

~75%

6-(4-Aminophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one Structure

6-(4-Aminopheny...

3-[4-(4-oxo-1,4-dihydropyridin-1-yl)benzoyl]butanoic acid Structure

3-[4-(4-oxo-1,4...

~90%

4-methyl-3-[4-(4-oxopyridin-1-yl)phenyl]-4,5-dihydro-1H-pyridazin-6-one Structure

4-methyl-3-[4-(...

4H-pyran-4-one Structure

6-(4-Aminophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one Structure

6-(4-Aminopheny...

~%

4-methyl-3-[4-(4-oxopyridin-1-yl)phenyl]-4,5-dihydro-1H-pyridazin-6-one Structure

4-methyl-3-[4-(...

Benzenebutanoic acid,4-(acetylamino)-g-oxo- Structure

Benzenebutanoic...

~%

4-methyl-3-[4-(4-oxopyridin-1-yl)phenyl]-4,5-dihydro-1H-pyridazin-6-one Structure

4-methyl-3-[4-(...

methyl 3-(4-acetamidobenzoyl)but-3-enoate Structure

methyl 3-(4-ace...

~%

4-methyl-3-[4-(4-oxopyridin-1-yl)phenyl]-4,5-dihydro-1H-pyridazin-6-one Structure

4-methyl-3-[4-(...

methyl 4-(4-aminophenyl)-4-oxo-3-(piperidin-1-ylmethyl)butanoate Structure

methyl 4-(4-ami...

~%

4-methyl-3-[4-(4-oxopyridin-1-yl)phenyl]-4,5-dihydro-1H-pyridazin-6-one Structure

4-methyl-3-[4-(...

3-(4-acetamidobenzoyl)-4-(N-piperidinyl)butanoic acid Structure

3-(4-acetamidob...

~%

4-methyl-3-[4-(4-oxopyridin-1-yl)phenyl]-4,5-dihydro-1H-pyridazin-6-one Structure

4-methyl-3-[4-(...

N-[4-(2-chloropropanoyl)phenyl]acetamide Structure

N-[4-(2-chlorop...

~%

4-methyl-3-[4-(4-oxopyridin-1-yl)phenyl]-4,5-dihydro-1H-pyridazin-6-one Structure

4-methyl-3-[4-(...

methyl 4-(4-acetamidophenyl)-3-methyl-4-oxobutanoate Structure

methyl 4-(4-ace...

~%

4-methyl-3-[4-(4-oxopyridin-1-yl)phenyl]-4,5-dihydro-1H-pyridazin-6-one Structure

4-methyl-3-[4-(...

DIETHYL 2-(1-(4-ACETAMIDOPHENYL)-1-OXOPROPAN-2-YL)MALONATE Structure

DIETHYL 2-(1-(4...

~%

4-methyl-3-[4-(4-oxopyridin-1-yl)phenyl]-4,5-dihydro-1H-pyridazin-6-one Structure

4-methyl-3-[4-(...

4-(4-Aminophenyl)-3-methyl-4-oxobutanoic acid hydrochloride Structure

4-(4-Aminopheny...

~%

4-methyl-3-[4-(4-oxopyridin-1-yl)phenyl]-4,5-dihydro-1H-pyridazin-6-one Structure

4-methyl-3-[4-(...

Acetanilide Structure

~%

4-methyl-3-[4-(4-oxopyridin-1-yl)phenyl]-4,5-dihydro-1H-pyridazin-6-one Structure

4-methyl-3-[4-(...

4-Hydroxypyridine Structure

4-Hydroxypyridine

~%

4-methyl-3-[4-(4-oxopyridin-1-yl)phenyl]-4,5-dihydro-1H-pyridazin-6-one Structure

4-methyl-3-[4-(...

Fluorobenzene Structure

~%

4-methyl-3-[4-(4-oxopyridin-1-yl)phenyl]-4,5-dihydro-1H-pyridazin-6-one Structure

4-methyl-3-[4-(...

2-chloro-1-(4-fluorophenyl)propan-1-one Structure

2-chloro-1-(4-f...

~%

4-methyl-3-[4-(4-oxopyridin-1-yl)phenyl]-4,5-dihydro-1H-pyridazin-6-one Structure

4-methyl-3-[4-(...

6-(4-acetamidophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one Structure

6-(4-acetamidop...

~%

4-methyl-3-[4-(4-oxopyridin-1-yl)phenyl]-4,5-dihydro-1H-pyridazin-6-one Structure

4-methyl-3-[4-(...

4-Hydroxypyridine Structure

4-Hydroxypyridine

N/A Structure

~%

4-methyl-3-[4-(4-oxopyridin-1-yl)phenyl]-4,5-dihydro-1H-pyridazin-6-one Structure

4-methyl-3-[4-(...

Chelidonic acid Structure

Chelidonic acid

6-(4-Aminophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one Structure

6-(4-Aminopheny...

~%

4-methyl-3-[4-(4-oxopyridin-1-yl)phenyl]-4,5-dihydro-1H-pyridazin-6-one Structure

4-methyl-3-[4-(...

1,5-Bis(dimethylamino)-1,4-pentadien-3-one Structure

1,5-Bis(dimethy...

6-(4-Aminophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one Structure

6-(4-Aminopheny...

~%

4-methyl-3-[4-(4-oxopyridin-1-yl)phenyl]-4,5-dihydro-1H-pyridazin-6-one Structure

4-methyl-3-[4-(...

Acetanilide Structure

~%

DIETHYL 2-(1-(4-ACETAMIDOPHENYL)-1-OXOPROPAN-2-YL)MALONATE Structure

DIETHYL 2-(1-(4...

methyl 3-(4-acetamidobenzoyl)but-3-enoate Structure

methyl 3-(4-ace...

~%

4-(4-Acetamidophenyl)-3-methyl-4-oxobutanoic acid Structure

4-(4-Acetamidop...

methyl 4-(4-acetamidophenyl)-3-methyl-4-oxobutanoate Structure

methyl 4-(4-ace...

Benzenebutanoic acid,4-(acetylamino)-g-oxo- Structure

Benzenebutanoic...

~%

4-(4-Acetamidophenyl)-3-methyl-4-oxobutanoic acid Structure

4-(4-Acetamidop...

methyl 4-(4-aminophenyl)-4-oxo-3-(piperidin-1-ylmethyl)butanoate Structure

methyl 4-(4-ami...

~%

4-(4-Acetamidophenyl)-3-methyl-4-oxobutanoic acid Structure

4-(4-Acetamidop...

3-(4-acetamidobenzoyl)-4-(N-piperidinyl)butanoic acid Structure

3-(4-acetamidob...

~%

4-(4-Acetamidophenyl)-3-methyl-4-oxobutanoic acid Structure

4-(4-Acetamidop...

Fluorobenzene Structure

(2R)-2-Chloropropanoyl chloride Structure

(2R)-2-Chloropr...

~92%

2-chloro-1-(4-fluorophenyl)propan-1-one Structure

2-chloro-1-(4-f...