Heterocyclic Building Blocks-Pyridazine

Heinisch, Gottfried published the artcilePyridazines. 77. Synthetic building blocks containing the 1,2-diazine moiety: N- and O-protected 3-(4-pyridazinyl)isoserines, COA of Formula: C5H4N2O, the publication is Heterocycles (1996), 43(5), 1057-1072, database is CAplus.

The syntheses of pyridazinylglycidates and pyridazinylimines as potential precursors of pyridazinylisoserine derivatives is described. Reactions of the imines I (R = PhCH₂, p-MeOC₆H₄) with α-silyloxyketene acetals, TBDMSOCH:C(OEt)OTBDMS (TBDMS = Me₃CSiMe₂), in the presence of zinc chloride led to isoserine derivatives II. The mixtures of diastereoisomers obtained were separated and configurations were determined by x-ray anal.

Heterocycles published new progress about 50901-42-3. 50901-42-3 belongs to pyridazine, auxiliary class Pyridazine,Aldehyde, name is Pyridazine-4-carbaldehyde, and the molecular formula is C5H4N2O, COA of Formula: C5H4N2O.

Referemce:
https://en.wikipedia.org/wiki/Pyridazine,
Pyridazine | C4H4N2 – PubChem

Chheda, Pratik R. published the artcileOne-Pot Reductive Alkylation of 2,4-Dihydroxy Quinolines and Pyridines, Computed Properties of 50901-42-3, the publication is Journal of Organic Chemistry (2021), 86(10), 7148-7162, database is CAplus and MEDLINE.

A one-pot, Hantzsch ester-mediated Knoevenagel condensation-reduction reaction has been developed for alkylation of a wide range of substituted 2,4-quinoline diols and 2,4-pyridine diols with aldehydes. The process is operationally simple to perform, scalable, and provides highly useful C-3 alkylated quinoline and pyridine diols in yields of 58-92%. The alkylation products can be converted to 2,4-dihaloquinoline and pyridine substrates for further functionalization.

Journal of Organic Chemistry published new progress about 50901-42-3. 50901-42-3 belongs to pyridazine, auxiliary class Pyridazine,Aldehyde, name is Pyridazine-4-carbaldehyde, and the molecular formula is C5H4N2O, Computed Properties of 50901-42-3.

Referemce:
https://en.wikipedia.org/wiki/Pyridazine,
Pyridazine | C4H4N2 – PubChem

Heinisch, Gottfried published the artcilePyridazines. Part 13. Substitution of the 1,2-diazine system with sym-trioxanyl radicals; a route to pyridazinecarbaldehydes, COA of Formula: C5H4N2O, the publication is Journal of Heterocyclic Chemistry (1980), 17(7), 1501-4, database is CAplus.

Pyridazine and 3-methylpyridazine were selectively attacked by sym-trioxanyl radicals at C-4 and/or C-5, but 4-methylpyridazine reacts under similar conditions to give not only the C-5 substitution product but also 3- and/or 6-trioxanylsubstituted methylpyridazines. Some of the reaction products were hydrolyzed to the formylmethylpyridazines.

Journal of Heterocyclic Chemistry published new progress about 50901-42-3. 50901-42-3 belongs to pyridazine, auxiliary class Pyridazine,Aldehyde, name is Pyridazine-4-carbaldehyde, and the molecular formula is C5H4N2O, COA of Formula: C5H4N2O.

Referemce:
https://en.wikipedia.org/wiki/Pyridazine,
Pyridazine | C4H4N2 – PubChem

Kosary, Judit published the artcileStudies of pyridazine-ring-containing compounds. 17. Synthesis of 6-methoxypyridazine-3-carboxaldehyde, HPLC of Formula: 89532-79-6, the publication is Magyar Kemiai Folyoirat (1983), 89(12), 567-8, database is CAplus.

The method of T. Nakagome (1962) for preparation of the title compound I was improved. 3-Methyl-6-chloropyridazine, purified on a Silica Gel 60 column, was oxidized with H₂O₂ to give 56% 3-methyl-6-chloropyridazine 2-oxide, which was methoxylated with NaOMe to give 90% 3-methyl-6-methoxypyridazine 2-oxide. Acetylation of the latter gave 78% (6-methoxy-3-pyridazinylmethyl)acetate which was heated with 10% HCl to give 87% 6-methoxypyridazine-6-methanol. Subsequent oxidation with MnO₂ gave 63% I. Alternatively, the oxidation was carried out with SeO₂ (65% yield). I was converted into 6-methoxy[1,2,3]triazolo[1,5-b]pyridazine (II) by the method of J. Kosari (1980).

Magyar Kemiai Folyoirat published new progress about 89532-79-6. 89532-79-6 belongs to pyridazine, auxiliary class Pyridazine,Alcohol,Ether, name is (6-Methoxypyridazin-3-yl)methanol, and the molecular formula is C6H8N2O2, HPLC of Formula: 89532-79-6.

Referemce:
https://en.wikipedia.org/wiki/Pyridazine,
Pyridazine | C4H4N2 – PubChem

Ogata, Masaru published the artcilePyridazines. II. 4-Methylpyridazine N-oxides, Recommanded Product: (6-Methoxypyridazin-3-yl)methanol, the publication is Chem. Pharm. Bull. (Tokyo) (1963), 35-9, database is CAplus.

4-Methylpyridazine as above gave 4-methylpyridazine 1-oxide (XVI), m. 83-4°, λ (EtOH) 266, 314 mμ (log ε 4.05, 3.61) and 2-oxide (XVII), b₄ 135° (no m.p. given), λ (EtOH) 265, 305 mμ (log ε 4.01, 3.52). 6-Chloro-4methyl-3(2H)-pyridazinone (2 g.), 50 cc. MeOH, 5 cc. 28% NH₄OH, 0.5 g. 10% Pd-C and H gave 1.2 g. 4-methyl-3(2H)pyridazinone (XVIII), m. 165-6° (EtOAc); similarly, 4 g. 6-chloro-5-methyl-3(2H)-pyridazinone gave 2.95 g. 5-methyl-3(2H)-pyridazinone (XIX), m. 160-1°. XVIII and POCl₃ as above gave 3-chloro-4-methylpyridazine (XX), m. 46-7° and XIX gave 6-chloro-4-methylpyridazine (XXI), m. 33°; XX and XXI with BzO₂H in CHCl₃ at room temperature gave the corresponding 1-oxides, m. 148-9° (XXII) and 127-8° (XXIII), resp. XXII (250 mg.), 10 cc. MeOH, 1 cc. MeOH-NH₃, 0.1 g. 10% Pd-C and H gave XVI; XXIII similarly gave XVII. The following were prepared by procedures described in the first part: 4-methyl-5-nitropyridazine 2-oxide, m. 144-5°; 4-methyl-5-aminopyridazine, m. 137-8°; 3-amino-5-methylpyridazine, m. 183-4°; and 4-amino-4-methylpyridazine, m. 200° (decomposition).

Chem. Pharm. Bull. (Tokyo) published new progress about 89532-79-6. 89532-79-6 belongs to pyridazine, auxiliary class Pyridazine,Alcohol,Ether, name is (6-Methoxypyridazin-3-yl)methanol, and the molecular formula is C6H8N2O2, Recommanded Product: (6-Methoxypyridazin-3-yl)methanol.

Referemce:
https://en.wikipedia.org/wiki/Pyridazine,
Pyridazine | C4H4N2 – PubChem

Ogata, Masaru published the artcilePyridazines. I. 3-Methylpyridazine N-oxides, HPLC of Formula: 89532-79-6, the publication is Chemical & Pharmaceutical Bulletin (1963), 29-35, database is CAplus and MEDLINE.

3-Methylpyridazine (I) (2.4 g.), 15 cc. glacial AcOH, and 7 cc. 30% H₂O₂ heated 3 h. at 70°, 7 cc. 30% H₂O₂ added, the whole heated 3 h. at 70°, 15 mL. H₂O added, the AcOH evaporated in vacuo, the residue neutralized with Na₂CO₃, extracted with CHCl₃, and the CHCl₃ solution passed over 27 g. alumina and eluted with C₆H₆ gave 630 mg. I 2-oxide (II), m. 83-4° (C₆H₆); elution with CHCl₃ gave 230 mg. I 1-oxide (III), m. 68.5-9.5° (C₆H₆). Under similar conditions, 1 g. 3-methyl-6-chloropyridazine gave 0.7 g. 2-oxide (IV), m. 163-4° (C₆H₆). IV (0.7 g.), 10 cc. MeOH, 1 cc. 28% NH₄OH, 0.1 g. 10 Pd-C, and H gave II. To 500 mg. II in 2 cc. concentrated H₂SO₄ with cooling was added slowly 0.5 cc. fuming HNO₃; the whole heated 6 h. at 100° and poured on ice gave with CHCl₃ extraction 610 mg. 3-methyl-5-nitropyridazine 2-oxide (IVa), m. 118-19° (C₆H₆). To MeONa (from 100 mg. Na and 10 cc. MeOH) was added 200 mg. IVa, the whole refluxed 1 h., evaporated to dryness, the residue treated with saturated NaCl, gave with CHCl₃ extraction 70 mg. 3-methyl-5-methoxypyridazine 2-oxide (V), m. 103-4° (C₆H₆). To 500 mg. IVa was added 5 cc. AcCl slowly, with cooling, the whole kept 2 h. at room temperature, evaporated to dryness and the residue treated with MeOH to give 150 mg. VI (C₅H₄N₃O₂Cl), m. 220° (decomposition) (MeOH); the structure of VI was not determined The MeOH filtrate from VI chromatographed on alumina gave 50 mg. 3-methyl-5-chloropyridazine 2-oxide (VII), m. 166-7° (C₆H₆). IVa (100 mg.) and 1 cc. concentrated HCl heated 2 h. at 100° and poured on H₂O gave, with CHCl₃ extraction, 50 mg. VII. To MeONa (from 10 mg. Na and 5 cc. MeOH) was added 60 mg. VII and the whole refluxed 1 h. to give with C₆H₆ extraction 20 mg. V; IV similarly gave 3-methyl-6-methoxypyridazine 2-oxide (VIII), m. 95-6°. 3-Methyl-6-methoxypyridazine (3 g.), 18 cc. glacial AcOH, and 6 cc. 30% H₂O₂ (added repetitively as above) gave 2.5 g. VIII. IV (500 mg.), 2 cc. concentrated H₂SO₄, and 0.5 cc. fuming HNO₃ as above gave 210 mg. 5-nitro derivative (IX), m. 103-3.5° (C₆H₆); similarly was obtained 5-nitro derivative (X) of VIII, m. 101-1.5° (MeOH). IX and X (500 mg.) treated as above with MeONa in MeOH gave 3-methyl-5,6-dimethoxypyridazine 2-oxide, m. 150-1° (C₆H₆). X (500 mg.), 10 cc. Ac₂O, and 500 mg. 10% Pd-C absorbed 4 mol H; the residue after filtration and evaporation of the filtrate was heated 10 min. at 100° with 5 cc. 6N HCl, the whole neutralized, saturated with HCl and extracted with CHCl₃ to give 180 mg. 3-methyl-5-amino-6-methoxypyridazine (Xa), m. 159-60° (EtOAc). Xa (150 mg.) and 2 cc. concentrated HI refluxed 3 h. and the whole cooled and neutralized with NaHCO₃ gave 4-amino-6-methyl-3(2H)-pyridazinone (XI), m. 260-1° (H₂O). To 1.7 g. 6-methyl-3(2H)-pyridazinone-4-carboxamide in 30 cc. 5% NaOH at 0° was added 10 g. 13.4% NaOCl dropwise and the whole added to 10 cc. boiling H₂O, the whole kept 20 min., cooled, neutralized with HCl and an excess of NH₄OH added gave 1.0 g. XI. IVa (300 mg.), 20 cc. MeOH, and 0.2 g. 10% Pd-C absorbed 3 mol H to give 150 mg. 3-methyl-5-aminopyridazine 2-oxide, m. 258° (MeOH); IX under similar conditions gave 3-methyl-5-aminopyridazine (XII), m. 162-3°, and XII was also obtained from X. VIII (1 g.) 10 cc. CHCl₃, and 2 g. POCl₃ refluxed 0.5 h., the whole concentrated, the residue neutralized with K₂CO₃, extracted with CHCl₃, the CHCl₃ distilled, and the residue in C₆H₆ passed over alumina and the eluate concentrated gave 650 g. 3-methyl-5-chloro-6-methoxypyridazine (XIII), m. 121-2° (petr. ether). IX (500 mg.) and 5 cc. AcCl as above gave a MeOH-insoluble unidentified C₆H₆N₃O₃Cl, m. 206-7° (decomposition); from the MeOH after chromatog. on alumina and elution with CHCl₃ was obtained 70 mg. 3-methyl-5-chloro-6-methoxypyridazine (XIV), m. 138-9°; alternately, 200 mg. VIII and 2 cc. concentrated HCl heated 2 h. at 100 gave 90 mg. XIV. To cold 400 mg. XIV in 10 cc. CHCl₃ was added 900 mg. PCl₃, the whole kept 24 h., poured on ice, neutralized, and chromatographed as above, gave 150 mg. XIII. VII (2 g.) and 10 cc. Ac₂O refluxed 2 h. and evaporated to dryness gave 1.1 g. 6-methoxy-3-pyridazinemethanol acetate (XV), m. 59-60° (cyclohexane); 500 mg. XV and 10 cc. 3N HCl heated 0.5 h. at 100°, neutralized with Na₂CO₃, the whole evaporated to dryness, and the residue extracted with EtOH gave 150 mg. 6-methoxy-3-pyridazinemethanol, m. 53-4° (C₆H₆). XV (1.4 g.) and 20 cc. 3N HCl heated 0.5 h. at 100°, the whole neutralized with Na₂CO₃, evaporated to dryness, the residue extracted with EtOH, the EtOH extract concentrated to dryness and the residue with 5 cc. concentrated H₂SO₄ and 2 g. K₂Cr₂O₇ heated 3 h. at 50° and then poured on ice gave 150 mg. 6-oxo-1,6-dihydro-3-pyridazinecarboxylic acid, m. 260° (H₂O). II. 4-Methylpyridazine N-oxides. Ibid. 35-9. 4-Methylpyridazine as above gave 4-methylpyridazine 1-oxide (XVI), m. 83-4°, λ (EtOH) 266, 314 mμ (log ε 4.05, 3.61) and 2-oxide (XVII), b₄ 135° (no m.p. given), λ (EtOH) 265, 305 mμ (log ε 4.01, 3.52). 6-Chloro-4methyl-3(2H)-pyridazinone (2 g.), 50 cc. MeOH, 5 cc. 28% NH₄OH, 0.5 g. 10% Pd-C and H gave 1.2 g. 4-methyl-3(2H)pyridazinone (XVIII), m. 165-6° (EtOAc); similarly, 4 g. 6-chloro-5-methyl-3(2H)-pyridazinone gave 2.95 g. 5-methyl-3(2H)-pyridazinone (XIX), m. 160-1°. XVIII and POCl₃ as above gave 3-chloro-4-methylpyridazine (XX), m. 46-7° and XIX gave 6-chloro-4-methylpyridazine (XXI), m. 33°; XX and XXI with BzO₂H in CHCl₃ at room temperature gave the corresponding 1-oxides, m. 148-9° (XXII) and 127-8° (XXIII), resp. XXII (250 mg.), 10 cc. MeOH, 1 cc. MeOH-NH₃, 0.1 g. 10% Pd-C and H gave XVI; XXIII similarly gave XVII. The following were prepared by procedures described in the first part: 4-methyl-5-nitropyridazine 2-oxide, m. 144-5°; 4-methyl-5-aminopyridazine, m. 137-8°; 3-amino-5-methylpyridazine, m. 183-4°; and 4-amino-4-methylpyridazine, m. 200° (decomposition).

Chemical & Pharmaceutical Bulletin published new progress about 89532-79-6. 89532-79-6 belongs to pyridazine, auxiliary class Pyridazine,Alcohol,Ether, name is (6-Methoxypyridazin-3-yl)methanol, and the molecular formula is C6H8N2O2, HPLC of Formula: 89532-79-6.

Referemce:
https://en.wikipedia.org/wiki/Pyridazine,
Pyridazine | C4H4N2 – PubChem

Westphal, Matthias V. published the artcileWater-compatible cycloadditions of oligonucleotide-conjugated strained allenes for DNA-encoded library synthesis, COA of Formula: C5H4N2O, the publication is Journal of the American Chemical Society (2020), 142(17), 7776-7782, database is CAplus and MEDLINE.

DNA-encoded libraries of small mols. are being explored extensively for the identification of binders in early drug-discovery efforts. Combinatorial syntheses of such libraries require water- and DNA-compatible reactions, and the paucity of these reactions currently limit the chem. features of resulting barcoded products. The present work introduces strain-promoted cycloadditions of cyclic allenes under mild conditions to DNA-encoded library synthesis. Owing to distinct cycloaddition modes of these reactive intermediates with activated olefins, 1,3-dipoles, and dienes, the process generates diverse mol. architectures from a single precursor. The resulting DNA-barcoded compounds exhibit unprecedented ring and topog. features, related to elements found to be powerful in phenotypic screening. DNA-encoded libraries of small mols. are being explored extensively for the identification of binders in early drug-discovery efforts. Combinatorial syntheses of such libraries require water- and DNA-compatible reactions, and the paucity of these reactions currently limit the chem. features of resulting barcoded products. The present work introduces strain-promoted cycloadditions of cyclic allenes under mild conditions to DNA-encoded library synthesis. Owing to distinct cycloaddition modes of these reactive intermediates with activated olefins, 1,3-dipoles and dienes, the process generates diverse mol. architectures from a single precursor. The resulting DNA-barcoded compounds exhibit unprecedented ring and topog. features-related to elements found to be powerful in phenotypic screening.

Journal of the American Chemical Society published new progress about 50901-42-3. 50901-42-3 belongs to pyridazine, auxiliary class Pyridazine,Aldehyde, name is Pyridazine-4-carbaldehyde, and the molecular formula is C8H6BrF3S, COA of Formula: C5H4N2O.

Referemce:
https://en.wikipedia.org/wiki/Pyridazine,
Pyridazine | C4H4N2 – PubChem

Haider, Norbert published the artcilePyridazines. LIX. Synthesis of c-annelated pyridazines from 3-amino-4-pyridazinecarbonitrile, Synthetic Route of 119581-52-1, the publication is Journal of Heterocyclic Chemistry (1991), 28(5), 1441-4, database is CAplus.

Annelated pyridazines I, II (R = Ph, R¹R² = O, X = NH; R = H, R¹ = H, R² = Ph, 3-pyridyl, X = O), and III were prepared from 3-amino-4-pyridazinecarbonitrile (IV). Thus, condensation of IV with hydrazine and treatment with Ac₂O gave I in 45% yield.

Journal of Heterocyclic Chemistry published new progress about 119581-52-1. 119581-52-1 belongs to pyridazine, auxiliary class Pyridazine,Nitrile,Amine, name is 3-Aminopyridazine-4-carbonitrile, and the molecular formula is C5H4N4, Synthetic Route of 119581-52-1.

Referemce:
https://en.wikipedia.org/wiki/Pyridazine,
Pyridazine | C4H4N2 – PubChem

Haider, Norbert published the artcilePyridazines. XXXV. Preparation of some novel pyrimido[4,5-c]pyridazine derivatives from 3-(alkylamino)- and 3-(arylamino)-4-pyridazinecarboxamides, COA of Formula: C5H4N4, the publication is Journal of Heterocyclic Chemistry (1988), 25(1), 119-24, database is CAplus.

Pyrimido[4,5-c]pyridazinediones I (R = Ph, PhCH₂; R¹R² = O), pyrimido[4,5-c]pyridazinones II (R = Ph, PhCH₂; R³ = H, Me, Et), and dihydropyrimido[4,5-c]pyridazinones I (R = Ph, PhCH₂, Me₂CH; R¹ = H, R² = Ph, 3-pyridyl) were prepared from 3-chloro-4-pyridazinecarbonitrile III (R⁴ = Cl) via amino carbonitriles III (R⁴ = NHR) and amino carboxamides. In addition, III (R⁴ = NH₂) was prepared from III (R⁴ = Cl), via the tetrazolo[1,5-b]pyridazine IV as the key intermediate.

Journal of Heterocyclic Chemistry published new progress about 119581-52-1. 119581-52-1 belongs to pyridazine, auxiliary class Pyridazine,Nitrile,Amine, name is 3-Aminopyridazine-4-carbonitrile, and the molecular formula is C5H4N4, COA of Formula: C5H4N4.

Referemce:
https://en.wikipedia.org/wiki/Pyridazine,
Pyridazine | C4H4N2 – PubChem

Dostal, Wolfgang published the artcilePyridazines. LI. On the reactivity of pyridazinecarboxaldehydes towards selected active-hydrogen compounds, Recommanded Product: Pyridazine-4-carbaldehyde, the publication is Journal of Heterocyclic Chemistry (1990), 27(5), 1313-21, database is CAplus.

Reactions of 3-pyridazinecarboxaldehyde (I) and 4-pyridazinecarboxaldehyde (II) with various active methylene carbanions were studied. The products obtained in Knoevenagel reactions, Horner-Emmons reactions, and Hantzsch-type reactions are presented. Thus, II was treated with CH₂(CN)₂ in refluxing EtOH to give 80% pyridazinylmethylenemalononitrile III. Further, I and MeCOCH₂CO₂Me were refluxed in EtOH and then treated with H₂NCMe:CHCO₂Et to give 52% the pyridazinyldihydropyridinedicarboxylate IV.

Journal of Heterocyclic Chemistry published new progress about 50901-42-3. 50901-42-3 belongs to pyridazine, auxiliary class Pyridazine,Aldehyde, name is Pyridazine-4-carbaldehyde, and the molecular formula is C5H4N2O, Recommanded Product: Pyridazine-4-carbaldehyde.

Referemce:
https://en.wikipedia.org/wiki/Pyridazine,
Pyridazine | C4H4N2 – PubChem