5469-70-5

Basic information

• Product Name: Pyridazin-3-amine
• Synonyms: 3-AMINOPYRIDAZINE,98.0+%(GC)(T);Pyridazin-3-ylamine;pyridazin-3-amine hydrochloride;Pyridazin-2-amine;Pyridazin-3-aMine/3-AMinopyridazine;Pyridazin-3-amine, 3-Amino-1,2-diazine;PYRIDAZIN-3-AMINE;3-AMINOPYRIDAZINE
• CAS NO: 5469-70-5
• Molecular Formula: C₄H₅N₃
• Molecular Weight: 95.1
• Product Categories: Amines;Pyrazines, Pyrimidines & Pyridazines;Pyrazines, Pyrimidines & Pyridazines;Building Blocks;Chemical Synthesis;Heterocyclic Building Blocks;Pyridazines;Heterocycles
• Mol File: 5469-70-5.mol
• Article Data: 21

Chemical Properties

• Melting Point: 171 °C
• Boiling Point: 326.19 °C at 760 mmHg
• Flash Point: 177.256 °C
• Appearance: White to pale yellow/Solid
• Density: 1.216 g/cm³
• Storage Temp.: Keep in dark place,Sealed in dry,Room Temperature
• Solubility: soluble in Methanol
• PKA: 4.88±0.10(Predicted)
• CAS DataBase Reference: Pyridazin-3-amine(CAS DataBase Reference)
• NIST Chemistry Reference: Pyridazin-3-amine(5469-70-5)
• EPA Substance Registry System: Pyridazin-3-amine(5469-70-5)

Safety Data

• Hazard Codes: Xi,Xn
• Statements: 22-36
• Safety Statements: 26-24/25
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 5469-70-5(Hazardous Substances Data)

Usage

Chemical Properties

White to yellow to light brown powder or crystal

Uses

It is an important raw material and intermediate used in organic synthesis, pharmaceuticals, agrochemicals and dyestuffs.

InChI:InChI=1/C4H5N3.ClH/c5-4-2-1-3-6-7-4;/h1-3H,(H2,5,7);1H

Synthetic route

6-chloro-pyridazin-3-ylamine (5469-69-2) → 3-aminopyridazine (5469-70-5)

Conditions	Yield
With sodium hydroxide; hydrogen; palladium 10% on activated carbon In tetrahydrofuran; water at 20℃; for 48h;	100%
With palladium on activated charcoal; hydrogen; sodium hydroxide In ethanol at 20℃; under 760.051 Torr; for 20h;	100%
With hydrogen; sodium hydroxide; palladium 10% on activated carbon In ethanol at 20℃; for 18h;	99.5%

3-chloropyridazine (1120-95-2) → 3-aminopyridazine (5469-70-5)

Conditions	Yield
With ammonium hydroxide In tetrahydrofuran at 150℃; for 36h;	50%
With ammonia at 180℃; under 117681 Torr;
With methanol; ammonia at 175℃;
With ethanol; ammonia at 175℃;

6-bromopyridazin-3-amine (88497-27-2) → 3-aminopyridazine (5469-70-5)

Conditions	Yield
With sodium hydroxide; palladium on activated charcoal Hydrogenation;

3-hydrazinyl pyridazine (40972-16-5) → 3-aminopyridazine (5469-70-5)

Conditions	Yield
With hydrogen; nickel for 2.5h;

9-tert-butylfluorene (17114-78-2) + C4H4N3(1-)*K(1+) → 3-aminopyridazine (5469-70-5) + potassium salt of 9-tert-butylfluorene (106358-48-9)

Conditions	Yield
In dimethyl sulfoxide at 24.9℃; Equilibrium constant;

4-aminopyridazine (20744-39-2) → 3-aminopyridazine (5469-70-5)

Conditions	Yield
palladium on charcoal In sodium hydroxide; ethanol

3-aminopyridazine (5469-70-5) + methyl 2-(4-(4-(4-(tert-butoxycarbonylamino)phenyl)thieno[3,2-d]pyrimidin-7-yl)phenyl)acetate (1421230-72-9) → 2-(4-(4-(4-(3-pyridazin-3-ylureido)phenyl)thieno[3,2-d]pyrimidin-7-yl)phenyl)acetic acid (1421230-37-6)

Conditions	Yield
Stage #1: 3-aminopyridazine; methyl 2-(4-(4-(4-(tert-butoxycarbonylamino)phenyl)thieno[3,2-d]pyrimidin-7-yl)phenyl)acetate With 4-Nitrophenyl chloroformate In 1,4-dioxane at 20℃; Stage #2: With water In tetrahydrofuran; methanol	100%

3-aminopyridazine (5469-70-5) + perfluorophenyl 1-(4-bromo-2-methoxyphenyl)-2-oxo-1,2-dihydroquinoline-6-sulfonate → 1-(4-bromo-2-methoxyphenyl)-2-oxo-N-(pyridazin-3-yl)-1,2-dihydroquinoline-6-sulfonamide

Conditions	Yield
With lithium hexamethyldisilazane In tetrahydrofuran at 0℃; for 0.333333h;	100%

3-aminopyridazine (5469-70-5) + 2-chloroethanal (107-20-0) → imidazo[1.2-b]pyridazine (766-55-2)

Conditions	Yield
at 70℃;	100%
In water; ethyl acetate at 85℃; for 2h; Solvent; Temperature;
In methanol; water at 87℃; for 1h; Solvent; Temperature; Concentration;

3-aminopyridazine (5469-70-5) + (5-bromo-pyridin-3-yl)-carbamic acid tert-butyl ester (361550-43-8) → tert-butyl (5-(pyridazin-3-ylamino)pyridin-3-yl)carbamate

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl-(2′,4′,6′-triisopropyl-3,6-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine; caesium carbonate In 1,4-dioxane at 90℃; for 16h; Inert atmosphere;	98%

3-aminopyridazine (5469-70-5) + 2,3-dibromopyridine (13534-89-9) → pyrido[3',2':4,5]imidazo[1,2-b]pyridazine + pyrido[2',3':4,5]imidazo[1,2-b]pyridazine

Conditions	Yield
With tris(dibenzylideneacetone)dipalladium (0); caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,2-dimethoxyethane at 140℃; for 30h;	A n/a B 97%

3-aminopyridazine (5469-70-5) + ortho-methylbenzoic acid (118-90-1) → 2-methyl-N-(pyridazin-3-yl)benzamide

Conditions	Yield
Stage #1: ortho-methylbenzoic acid With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 0.166667h; Inert atmosphere; Stage #2: 3-aminopyridazine With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 60℃; Inert atmosphere;	96%

3-aminopyridazine (5469-70-5) + N,N-dimethyl-formamide dimethyl acetal (4637-24-5) → N,N-dimethyl-N'-pyridazin-3-yl-formamidine (35053-54-4)

Conditions	Yield
for 2h; Reflux;	95%
In toluene at 20 - 85℃;	91%
In toluene at 20 - 85℃;	91%
In toluene for 2h; Heating;
In methanol at 45℃; for 6h; Solvent; Temperature;

3-aminopyridazine (5469-70-5) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → N,N-dimethyl-N'-pyridazin-3-yl-formamidine (35053-54-4)

Conditions	Yield
In N,N-dimethyl acetamide for 2h; Reflux;	95%

3-aminopyridazine (5469-70-5) + Methyl (Z)-2-<(benzyloxycarbonyl)amino>-3-dimethylaminopropenoate (219739-90-9) → 3-<(Benzyloxycarbonyl)amino>-4H-pyrimido<1,2-b>pyridazin-4-one (225112-17-4)

Conditions	Yield
With acetic acid for 6h; Reflux;	93%
With sodium acetate; acetic acid 1.) reflux, 3.5 h, 2.) reflux, 4 h; Yield given; Multistep reaction;

3-aminopyridazine (5469-70-5) + 2-chloro-3-iodo-quinoline (128676-85-7) → pyridazino[6',1':2,3]imidazo[4,5-b]quinoline

Conditions	Yield
With caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; palladium diacetate In toluene for 17h; Heating;	93%

3-aminopyridazine (5469-70-5) + 1,1,1-trifluoro-N-(pyridin-2-yl)-N-((trifluoromethyl)-sulfonyl)methanesulfonamide (145100-50-1) → 3-N'-monotrifluoromethanesulfonamidopyridazine

Conditions	Yield
In acetonitrile at 60℃; Inert atmosphere;	90%

3-aminopyridazine (5469-70-5) + phenyl chloroformate (1885-14-9) → phenyl pyridazin-3-ylcarbamate (1020327-61-0)

Conditions	Yield
With pyridine In acetonitrile at 0℃; for 1h;	87%
With pyridine In acetonitrile at 0 - 20℃;	74%
With pyridine In tetrahydrofuran; acetonitrile Product distribution / selectivity;	70%

3-aminopyridazine (5469-70-5) + methyl (Z)-2-benzoylamino-3-dimethylaminopropenoate (125008-68-6) → 3-benzoylamino-4H-pyrimido[1,2-b]pyrdazin-4-one

Conditions	Yield
With acetic acid for 4.5h; Condensation; Heating;	86%

3-aminopyridazine (5469-70-5) + 2-chloro-6-methylphenyl isothiocyanate (19241-34-0) → 1-(2-Chloro-6-methyl-phenyl)-3-pyridazin-3-yl-thiourea

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide 1) 0 deg C to r.t., 2) r.t., 3 h;	85%

3-aminopyridazine (5469-70-5) + 2,3-dibromoquinoline (13721-00-1) → 3-bromo-N-(pyridazin-3-yl)quinolin-2-amine

Conditions	Yield
With caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; tris(dibenzylideneacetone)dipalladium (0) In 1,2-dimethoxyethane for 7h; Heating;	84%

3-aminopyridazine (5469-70-5) + (P)-perfluorophenyl 1-(5-fluoro-2-methoxy-4-(3,3,3-trifluoropropyl)phenyl)-2-oxo-1,2-dihydroquinoline-6-sulfonate → (P)-1-(5-fluoro-2-methoxy-4-(3,3,3-trifluoropropyl)phenyl)-2-oxo-N-(pyridazin-3-yl)-1,2-dihydroquinoline-6-sulfonamide

Conditions	Yield
With lithium hexamethyldisilazane In tetrahydrofuran; dimethyl sulfoxide for 0.25h; Cooling with ice;	84%

3-aminopyridazine (5469-70-5) + 2,6-dichlorobenzenesulfonyl chloride (6579-54-0) → 9-chlorobenzo[e]pyridazino[1,6-b][1,2,4]thiadiazine 10,10-dioxide

Conditions	Yield
Stage #1: 3-aminopyridazine; 2,6-dichlorobenzenesulfonyl chloride With potassium carbonate In acetonitrile at 20℃; for 10h; Stage #2: With copper(l) iodide In acetonitrile at 80℃; for 3h; Ullmann Condensation; chemoselective reaction;	84%

3-aminopyridazine (5469-70-5) + 2-chloro-6-methylphenyl isocyanate (40398-01-4) → 1-(2-Chloro-6-methyl-phenyl)-3-pyridazin-3-yl-urea

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide 1) 0 deg C to r.t., 2) r.t., 3 h;	83%

3-aminopyridazine (5469-70-5) + [1,2,4]Oxadiazolo[2,3-b]pyridazine-2-thione (71344-17-7) → 1,3-di(3-pyridazinyl)urea (71344-18-8)

Conditions	Yield
In dimethyl sulfoxide at 80 - 90℃; for 2h;	82%

3-aminopyridazine (5469-70-5) + dichlorobenzenesulfonyl chloride (82417-45-6) → 6-chlorobenzo[e]pyridazino[1,6-b][1,2,4]thiadiazine 10,10-dioxide

Conditions	Yield
Stage #1: 3-aminopyridazine; dichlorobenzenesulfonyl chloride With potassium carbonate In acetonitrile at 20℃; for 10h; Stage #2: With copper(l) iodide In acetonitrile at 80℃; for 3h; Ullmann Condensation; chemoselective reaction;	82%

3-aminopyridazine (5469-70-5) + 2,3-dibromopyridine (13534-89-9) → N-(3-bromopyridin-2-yl)pyridazin-3-amine

Conditions	Yield
With tris(dibenzylideneacetone)dipalladium (0); caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,2-dimethoxyethane for 7h; Heating;	81%

3-aminopyridazine (5469-70-5) + 3-(5-bromo-pyridin-2-yloxy)-azetidine-1-carboxylic acid 4-nitro-phenyl ester (1186234-54-7) → 3-(5-bromo-pyridin-2-yloxy)-azetidine-1-carboxylic acid pyridazin-3-ylamide (1186234-62-7)

Conditions	Yield
Stage #1: 3-aminopyridazine With sodium hydride In N,N-dimethyl-formamide; mineral oil Inert atmosphere; Cooling with ice; Stage #2: 3-(5-bromo-pyridin-2-yloxy)-azetidine-1-carboxylic acid 4-nitro-phenyl ester In N,N-dimethyl-formamide; mineral oil at 20℃; Inert atmosphere; Cooling with ice;	80%

3-aminopyridazine (5469-70-5) + 2-iodopyrazine (32111-21-0) → C8H7N5

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 90℃; for 3h; Inert atmosphere;	80%
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 90℃; for 3h; Inert atmosphere;	80%
Stage #1: 3-aminopyridazine; 2-iodopyrazine With caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane for 0.166667h; Inert atmosphere; Stage #2: With tris-(dibenzylideneacetone)dipalladium(0) In 1,4-dioxane at 90℃; for 3h;	80%

3-aminopyridazine (5469-70-5) + 2-chloro-3-(2-(methylthio)benzo[d]thiazol-6-yl)propanal → 6-(imidazo[1,2-b]pyridazin-3-ylmethyl)-2-(methylthio)benzo[d]thiazole

Conditions	Yield
In butan-1-ol for 15h; Reflux;	80%

3-aminopyridazine (5469-70-5) + 2-chloro-4,6-dimethoxy-1 ,3,5-triazine (3140-73-6) + (3S)-2-[(2R)-2-({formyl[(phenylmethyl)oxy]amino}methyl)heptanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid (1398752-89-0) → Phenylmethyl (3S)-2-[(2R)-2-({formyl[(phenylmethyl)oxy]amino}methyl)heptanoyl]-3-[(3-pyridazinylamino)carbonyl]-1-pyrazolidinecarboxylate (1398753-00-8)

Conditions	Yield
With 4-methyl-morpholine In acetonitrile	79%

3-aminopyridazine (5469-70-5) + C21H25FO3 → 3-((13S,15R)-3-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(pyridazin-3-yl)propanamide

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran at 50℃; for 3.5h;	79%
With pyridine; triphenylphosphine In dichloromethane; ethyl acetate at 20℃; Inert atmosphere;

Upstream product

• 5469-69-2 6-chloro-pyridazin-3-ylamine 
• 88497-27-2 6-bromopyridazin-3-amine 
• 20744-39-2 4-aminopyridazine 
• 40972-16-5 3-hydrazinyl pyridazine 
• 1120-95-2 3-chloropyridazine 
• 17114-78-2 9-tert-butylfluorene 

Downstream Products

• 515-62-8 4-amino-N-pyridazin-3-yl-benzenesulfonamide 
• 106840-27-1 N-acetyl-sulfanilic acid pyridazin-3-ylamide 
• 147362-90-1 tert-butyl N-(3-pyridazinyl)carbamate 
• 1844-54-8 2-phenylimidazo<1,2-b>pyridazine 
• 453548-65-7 1-(imidazo[1,2-b]pyridazin-3-yl)ethanone 
• 1283548-60-6 N-(2,4-dimethoxybenzyl)pyridazin-3-amine 
• 1354786-61-0 3-chloro-4-fluoro-N-(pyridazin-3-yl)benzenesulfonamide 
• 1208552-67-3 C₁₅H₁₆ClN₃O 
• 1020327-61-0 phenyl pyridazin-3-ylcarbamate 
• 33471-48-6 3-aminopyridazine 2-oxide 
• 104691-62-5 2-(4-Acetamido-phenyl)-imidazo[1,2-b]pyridazine 
• 896125-72-7 2-bromo-N-pyridazin-3-yl-acetamide 

Relevant articles and documents

Development of new highly potent imidazo[1,2-b[pyridazines targeting Toxoplasma gondii calcium-dependent protein kinase 1

Using a structure-based design approach, we have developed a new series of imidazo[1,2-b]pyridazines, targeting the calcium-dependent protein kinase-1 (CDPK1) from Toxoplasma gondii. Twenty derivatives were thus synthesized. Structure-activity relationships and docking studies confirmed the binding mode of these inhibitors within the ATP binding pocket of TgCDPK1. Two lead compounds (16a and 16f) were then identified, which were able to block TgCDPK1 enzymatic activity at low nanomolar concentrations, with a good selectivity profile against a panel of mammalian kinases. The potential of these inhibitors was confirmed in vitro on T. gondii growth, with EC50 values of 100 nM and 70 nM, respectively. These best candidates also displayed low toxicity to mammalian cells and were selected for further in vivo investigations on murine model of acute toxoplasmosis.

IMIDAZOTRIAZINONE COMPOUNDS

The present invention provides imidazotriazinone compounds which are inhibitors of phosphodiesterase 9 and pharmaceutically acceptable salt thereof. The present invention further provides processes, pharmaceutical compositions, pharmaceutical preparations and pharmaceutical use of the compounds in the treatment of PDE9 associated diseases or disorders in mammals, including humans.

IMIDAZOTRIAZINONE COMPOUNDS

The present invention provides imidazotriazinone compounds which are inhibitors of phosphodiesterase 9. The present invention further provides processes, pharmaceutical compositions, pharmaceutical preparations and pharmaceutical use of the compounds in the treatment of PDE9 associated diseases or disorders in mammals, including CNS or neurodegeneration disorder.