Tag: M.W=100-150

Nakagome, Takenari published the artcileSyntheses of pyridazine derivatives. III. Structure of 3-substituted 6-methylpyridazine N-oxides., Computed Properties of 89532-79-6, the publication is Yakugaku Zasshi (1962), 249-53, database is CAplus and MEDLINE.

3-Methylpyridazine (I) (9.7 g.) in 140 ml. AcOH, 14 ml. H₂O, and 14 ml. 30% H₂O₂ heated 8 hrs. at 80°, the AcOH removed, the residue in H₂O made alk. with Na₂CO₃, and the product extracted with CHCl₃ gave 9.3 g. liquid, b_0.5 110-13°; this in 1:1 C₆H₆CHCl₃ chromatographed through Al₂O₃ and the first eluate concentrated gave 3.9 g. I 2-oxide (II) m. 85-6° and the last effluent gave 4 g. I 1-oxide (III), m. 68-9°. Catalytic reduction of 0.1 g. II in 30 ml. MeOH with 0.5 g. 5% Pd-C absorbed 22 ml. H and gave 0.2 g. I (picrate m. 148-9°). Similarly, III yielded I. 3-Methyl-6-chloropyridazine (IV) (30 g.) and 420 ml. CHCl₃ containing 30 g. BzO₂H kept 3 days at room temperature, the solution concentrated and the residue washed with Et₂O gave 29 g. 3-chloro-6-methylpyridazine 1-oxide (V), m. 160-1°. Catalytic reduction of 2 g. V in 2 ml. 28% NH₄OH and 20 ml. H₂O at room temperature absorbed 1 mole H in 50 min. and gave 1.2 g. II, m. 85-6°; picrate m. 103-4°. 3-Methoxy-O-methylpyridazine (VI) (44 g.), 350 ml. AcOH, and 50 ml. 30% H₂O₂ kept 1 week at 40-5°, the AcOH removed, the residue in H₂O made alk. with Na₂CO₃ and the product extracted with CHCl₃ gave 41 g. VI 1-oxide (Via) m. 98-9° (AcOEt). VIa (0.7 g.) in 20 ml. 5% NaOH heated 1 hr., the solution acidified with HCl, evaporated to dryness, and the product extracted with EtOH gave 0.3 g. 6-methyl-3-pyridazinol 1-oxide, m. 201-2°. VIa (9 g.) and 60 ml. Ac₂O heated 2 hrs. at 100°, the Ac₂O removed, the residue made alk. with Na₂CO₃ and the product extracted with CHCl₃ gave 9 g. 6-methoxy-3-pyridazinemethyl acetate (VII), m. 59-61°. VI (8 g.) and 60 ml. 10% HCl refluxed 30 min. and the product treated as usual gave 4 g. 6-methoxy-3-pyridazinemethanol (VIII), m. 55-6.5°. VIII (1.6 g.), 0.8 g. SeO₂ and 25 ml. dioxane stirred 4 hrs. at 70-5°, the solution concentrated, and the residue treated with NH₂CONHNH₂ gave 6-methoxy-3-pyridazinealdehyde semicarbazone, m. 248° (decomposition).

Yakugaku Zasshi 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, Computed Properties of 89532-79-6.

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

Nakagome, Takenari published the artcileSyntheses of pyridazine derivatives. II. 3-Methoxy-6-pyridazinol 1-oxide, Recommanded Product: (6-Methoxypyridazin-3-yl)methanol, the publication is Yakugaku Zasshi (1962), 244-8, database is CAplus and MEDLINE.

cf. CA 55, 21134c. 3-Chloro-6-methoxypyridazine (I) (7.3 g.) in 50 mL. AcOH treated with 24 mL. 30% H₂O₂, kept 5 h. at 70°, the solution concentrated in vacuo, the residue made alk. with Na₂CO₃ and the product extracted with CHCl₃ gave 1.4 g. 3-methoxy-6-chloropyridazine 1-oxide (II), m. 157-8° (C₆H₆). The mother liquor from washing II with 2N NaOH gave 0.4 g. 3-methoxy-6(1H)-pyridazinone (III), plates, m. 162-3° (AcOEt). A solution of 18 g. BzO₂H in 337 mL. CHCI₃ treated with 14.5 g. I, kept 3 days at room temperature and the product treated as above gave 14.3 g. II, m. 157-8°. I (3 g.), 20 mL. AcOH, and 3.4 g. AcOK in a sealed tube heated 1.5 h. at 140-50° and the AcOH removed gave 3.6 g. III, m. 162-3°. III (4 g.) and 30 mL. POCl₃ heated 30 min. at 100° the product poured into ice-H₂O and extracted with Et₂O gave 1.5 g. 3,6-dichloropyridazine (IV), m. 68-9°. Catalytic reduction of 0.5 g. II in 3 mL. 28% NH₄OH and 30 mL. MeOH with 0.05 g. 10% Pd-C absorbed 77 mL. H and gave 0.35 g. 3-methoxypyridazine 1-oxide (V), m. 79-80°. Catalytic reduction of 0.5 g. II in 3 mL. 28% NH₄OH and 30 mL. MeOH with Pd-C (from 10 mL. 1% PdCl₂ and 0.5 g. C) absorbed 160 mL. H in 15 min. and gave 0.5 g. 3-methoxypyridazine; picrate m. 111°. II (3.2 g.), 12 mL. AcOH, and 1.64 g. AcONa in a sealed tube heated 1 h. at 150-60° and the product concentrated gave 1.64 g. 1-hydroxy-3-methoxy-5(1H)-pyridazinone (VI), m. 178-9°. A solution of 29.5 g. 3,6-dimethoxypyridazine I-oxide in 400 mL. 2N HCl heated 20 min. at 80-90° and the solution concentrated gave 25.3 g. VI, m. 178-9°. VI (2.8 g.), 2.54 g. BzCl, 0.46 g. Na and 30 mL. MeOH in a sealed tube heated 2 h. at 100° the solution concentrated and the residue extracted with CHCl₃ gave 3.1 g. 1-benzoyloxy-3-methoxy-6(1H)pyridazinone (VII), m. 86.5-87°. VI (2 g.), 2.5 g. MeI, Ag₂O (from 3 g. AgNO₃), and 20 mL. MeOH in a sealed tube heated 2 h. at 100° and the solution concentrated gave 100% 1,3-dimethoxy-6(1H)-pyridazinone, m. 66-7°. A solution of 250 mL. dry C₆H₆, 20.6 g. PhCH₂OH, and 4.4 g. Na, refluxed 1 h., after disappearance of Na, with 20 g. 3-chloropyridazine, and the product distilled gave 18 g. 3-benzyloxypyridazine (VIII), b_0.15 120-5°, m. 49-50°. VIII (6 g) and 84.5 mL. CHCl₃ containing 4.46 g. BzO₂H kept 2 days at room temperature gave 100% VIII I-oxide (VIIIa), m. 118-18.5°. Catalytic reduction of 0.5 g. VIIIa in 30 mL. MeOH with 0.05 g. 10% Pd-C absorbed 64 mL. H in 5 min.and gave 3-pyridazinol 1-oxide, m. 201-2° (decomposition). Catalytic reduction of 0.5 g. VIIIa in 30 mL. MeOH with 0.2 g. 10% Pd-C absorbed 128 mL. H in 15 min. and gave 0.25 g. 3(2H)-pyridazinone-H₂O, m. 74°. IV (21 g.) and 240 mL. CHCl₃ containing 18.7 g. BzO₂H kept 2 days at room temperature and the product concentrated gave 10.4 g. IV 1-oxide, m. 110-12°. IV 1-oxide (1 g.) and 0.33 g. 22.6% MeONa-MeOH heated several min. on a water bath, the solution acidified with AcOH and the product extracted with CHCl₃ gave 0.6 g. II, m. 155-7°.

Yakugaku Zasshi 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

Heinisch, G. published the artcileSynthesis and reactions of pyridazine derivatives. II. 4-Hydroxymethylpyridazine, Category: pyridazine, the publication is Monatsh. Chem. (1973), 104(5), 1354-9, database is CAplus.

4-(Hydroxymethyl)pyridazine (I) was obtained together with Et 2,5-dihydropyridazine-4-carboxylate by LiAlH4 or NaBH4 reduction of Et 4-pyridazinecarboxylate, the ratios depending on the reaction conditions. Reduction of 4-pyridazinecarboxaldehyde or 4-acetylpyridazine with NaBH4 gave I or 4-(1-hydroxyethyl)pyridazine, resp., in quant. yield. Treatment of I with SOCl2 gave 4-(chloromethyl)pyridazine.

Monatsh. Chem. 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, Category: pyridazine.

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

Floyd, David M. published the artcileHit-to-Lead Studies for the Antimalarial Tetrahydroisoquinolone Carboxanilides, Application In Synthesis of 50901-42-3, the publication is Journal of Medicinal Chemistry (2016), 59(17), 7950-7962, database is CAplus and MEDLINE.

Phenotypic whole-cell screening in erythrocytic co-cultures of Plasmodium falciparum identified a series of dihydroisoquinolones that possessed potent anti-malarial activity against multiple resistant strains of P. falciparum in vitro and show no cytotoxicity to mammalian cells. Systematic structure-activity studies revealed relationships between potency and modifications at N-2, C-3 and C-4. Careful structure-property relationship studies, coupled with studies of metabolism, addressed the poor aqueous solubility and metabolic vulnerability, as well as potential toxicol. effects, inherent in the more potent primary screening hits such as (I). Analogs (II) and (+)-SJ733 (13i), with structural modifications at each site, were shown to possess excellent anti-malarial activity in vivo. The (+)-(3S,4S) enantiomer of 13i and similar analogs were identified as the more potent. Based on these studies, the authors have selected (+)-13i for further study as a preclin. candidate.

Journal of Medicinal 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, Application In Synthesis of 50901-42-3.

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

Cacciari, Barbara published the artcileFacile and versatile route to the synthesis of fused 2-pyridones: useful intermediates for polycyclic systems, Safety of 3-Aminopyridazine-4-carbonitrile, the publication is Synthetic Communications (2006), 36(9), 1177-1183, database is CAplus.

The reaction of various heteroaromatic amino nitriles with di-Et malonate under basic conditions is reported. This reaction affords a series of different highly functionalized 2-pyridone condensed systems, which can be suitable intermediates in the construction of polyheterocyclic structures.

Synthetic Communications 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, Safety of 3-Aminopyridazine-4-carbonitrile.

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

Liu, Yuji published the artcileConstruction of Bicyclic 1,2,3-Triazine N-Oxides from Aminocyanides, HPLC of Formula: 119581-52-1, the publication is Organic Letters (2021), 23(3), 734-738, database is CAplus and MEDLINE.

Using a facile and cost-effective method, nine bicyclic 1,2,3-triazine 2-oxides were synthesized from o-aminocyanide substrates through an unusual nitration cyclization. The reaction mechanism was studied exptl. and theor. Moreover, nine 1,2,3-triazine 3-oxides were also obtained in good yields.

Organic Letters 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, HPLC of Formula: 119581-52-1.

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

Heinisch, G. published the artcilePyridazines. Part 55. Electron-ionization mass spectrometry of selected monosubstituted pyridazines, Category: pyridazine, the publication is Scientia Pharmaceutica (1991), 59(2), 111-13, database is CAplus.

The electron-ionization mass spectrometric fragmentations of 20 3- or 4-substituted pyridazines (I, R or R¹ = H, CH₂OH, CH:NOH, CN, COOH, CONH₂, COOMe, COOEt, CHO, COMe, COEt) are given.

Scientia Pharmaceutica 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, Category: pyridazine.

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

Varney, Michael D. published the artcileSynthesis and Biological Evaluation of Novel 2,6-Diaminobenz[cd]indole Inhibitors of Thymidylate Synthase Using the Protein Structure as a Guide, Recommanded Product: Pyridazine-4-carbaldehyde, the publication is Journal of Medicinal Chemistry (1995), 38(11), 1892-903, database is CAplus and MEDLINE.

The design, synthesis, and biochem. and biol. evaluations of a novel series of 2,6-diaminobenz[cd]indoles I (R¹, R² = H, Me; X = H; N = methine, nitrogen) of were prepared as inhibitors of human thymidylate synthase (TS) are described. The compounds are characterized by having either a pyridine or pyridazine ring in place of the (phenylsulfonyl)morpholinyl group of the known inhibitor N⁶-[4-(morpholinosulfonyl)benzyl]-N⁶-methyl-2,6-diaminobenz[cd]indole glucuronate. Active compounds from this series showed human TS inhibition constants below the 10 nM level and were potent, selective submicromolar antitumor agents in cell culture. The compounds were synthesized by reductive alkylation of a substituted 6-aminobenz[cd]indole or reductive cyclization of a substituted 1-cyano-8-nitronaphthalene.

Journal of Medicinal 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 C9H8O4, Recommanded Product: Pyridazine-4-carbaldehyde.

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

Yamane, Daiki published the artcileSelective covalent targeting of SARS-CoV-2 main protease by enantiopure chlorofluoroacetamide, Recommanded Product: Pyridazine-4-carbaldehyde, the publication is Chemical Science (2022), 13(10), 3027-3034, database is CAplus and MEDLINE.

An irreversible SARS-CoV-2 M^pro inhibitor possesseschlorofluoroacetamide (CFA) as a warhead for the covalent modification of M^pro. Ugi multicomponent reaction using chlorofluoroacetic acid enabled the rapid synthesis of dipeptidic CFA derivatives RC(O)N(C₆H₅R¹)CH(R²)C(O)NHR³ (R = Ac, ethenyl, difluoroacetyl, furan-2-yl; R¹ = i-Pr, t-Bu, 1-methylcyclohexyl, etc.; R² = pyridin-3-yl, pyridazin-4-yl, pyridazin-3-yl, etc.; R³ = t-Bu, isoquinolin-7-yl, 2-(3-fluorophenyl)ethyl, etc.) that identified (SR)/(RR)/(RS)(SS)-2-chloro-2-fluoro-N-(2-[(3-fluorophenethyl)amino]-2-oxo-1-(pyrimidin-5-yl)ethyl)-N-[4-(pentafluoro-lmbda6-sulfaneyl)phenyl]acetamide as a potent inhibitor of SARS-CoV-2 M^pro. Among the four stereoisomers, (R)-2-chloro-2-fluoro-N-((R)-2-[(3-fluorophenethyl)amino]-2-oxo-1-(pyrimidin-5-yl)ethyl)-N-[4-(pentafluoro-lamda6-sulfaneyl)phenyl]acetamide exhibited a markedly higher inhibitory activity against M^pro than the other isomers. Reaction kinetics and computational docking studies suggest that the R configuration of the CFA warhead is crucial for the rapid covalent inhibition of M^pro. These findings highlight the prominent influence of the CFA chirality on the covalent modification of proteinous cysteines and provide the basis for improving the potency and selectivity of CFA-based covalent inhibitors.

Chemical Science 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 C4H8Cl2S2, Recommanded Product: Pyridazine-4-carbaldehyde.

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

Heinisch, Gottfried published the artcilePyridazines. 7. Preparation of pyridazine-3-carboxaldehyde: synthesis and reactivity studies, Formula: C5H4N2O, the publication is Monatshefte fuer Chemie (1977), 108(1), 213-24, database is CAplus.

MnO2-oxidation of 3-pyridazinemethanol gave 3-pyridazinecarboxaldehyde (I). Properties of I and its reactions with NH compounds and methylpiridazines were studied. Reaction of I with 3-methylpiridazine gave mainly products of aldol addition II and III. Elimination of H2O from II gave the alkene IV. Isolation of dipyridazinylethane V as main product of reaction of I with 4-methylpiperazine however shows, that thermally induced dismutation cannot be excluded also on pyridazinyl-3-carbinols.

Monatshefte fuer Chemie 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, Formula: C5H4N2O.

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