1603-41-4

Usage

Chemical Properties

light yellow crystalline flakes

Uses

Intermediate.

Safety Profile

Poison by ingestion,subcutaneous, and skin contact routes. When heated todecomposition it emits toxic vapors of NOx.

Purification Methods

Crystallise it from acetone. [Beilstein 22/9 V 289.]

InChI:InChI=1/C6H8N2/c1-5-2-3-6(7)8-4-5/h2-4H,1H3,(H2,7,8)/p+1

Synthetic route

2-Bromo-5-methylpyridine → (5-methyl-pyridin-2-yl)amine (1603-41-4)

Conditions	Yield
With [Cu2(2,7-bis(pyridin-2-yl)-l,8-naphthyridine)(OH)(CF3COO)3]; tetrabutylammomium bromide; ammonia; caesium carbonate In water at 110 - 120℃; for 16h; Sealed tube;	100%
With ammonium hydroxide; potassium phosphate; 1-(5,6,7,8-tetrahydroquinolin-8-yl)-2-methylpropan-1-one; copper(I) bromide In dimethyl sulfoxide at 110℃; for 24h; Inert atmosphere; Sealed tube;	85%

3-Methylpyridine (108-99-6) → (5-methyl-pyridin-2-yl)amine (1603-41-4) + 3-methylpyridin-2-ylamine (1603-40-3)

Conditions	Yield
With sodium amide; xylene
With ammonia; sodium; ethanolamine In toluene at 60 - 170℃; under 22502.3 - 41254.1 Torr; Pressure; Temperature; Autoclave; Inert atmosphere; Large scale;	A 1928 g B 144 g

3-picoline-N-oxide (1003-73-2) → (5-methyl-pyridin-2-yl)amine (1603-41-4)

Conditions	Yield
With hydrogenchloride; 4-chloro-2-methyl-1,3-benzoxazin-2-yl polystyrene 1.) ethylene chloride, reflux, 24 h, 2.) reflux, 20 h; Yield given. Multistep reaction;
Multi-step reaction with 2 steps 1: CH2Cl2 / Heating 2: conc. HCl View Scheme
Multi-step reaction with 2 steps 1: 84 percent / CHCl3 / 4 h / Heating 2: 98 percent / conc. HCl / 8 h / Heating View Scheme
With thionyl chloride; trimethylamine
With sodium hydroxide; thionyl chloride; hydrogen bromide; trimethylamine In dichloromethane; ethyl acetate

3-Methylpyridine (108-99-6) → (5-methyl-pyridin-2-yl)amine (1603-41-4)

Conditions	Yield
With sodium amide In ethanol at 66℃; for 2.16667h; Temperature; Reflux;
Multi-step reaction with 3 steps 1: acetic acid; dihydrogen peroxide / 6 h / 80 °C 2: dinitrogen pentoxide / dichloromethane / 4 h / 40 °C 3: zinc; formic acid / dichloromethane; methanol / 2 h / 75 °C View Scheme

2-chloro-5-methylpyridine (18368-64-4) → (5-methyl-pyridin-2-yl)amine (1603-41-4)

Conditions	Yield
With dicyclohexyl(2',4',6'-triisopropyl-5-methoxy-3,4,6-trimethyl-[1,1'-biphenyl]-2-yl)phosphine; C50H70NO4PPdS; C50H70NO4PPdS; dicyclohexyl(2',4',6'-triisopropyl-4-methoxy-3,5,6-trimethyl-[1,1'-biphenyl]-2-yl)phosphine; ammonia; sodium t-butanolate In 1,4-dioxane at 50℃; for 24h; Reagent/catalyst; Inert atmosphere;	75%

2-nitro-5-methylpyridine-N-oxide (100047-39-0) → (5-methyl-pyridin-2-yl)amine (1603-41-4)

Conditions	Yield
With formic acid; zinc In methanol; dichloromethane at 75℃; for 2h; Time; Temperature;

sodium sulfate (7757-82-6) + 2-dimethylamino-5-methylpyridine → (5-methyl-pyridin-2-yl)amine (1603-41-4)

Conditions	Yield
With pyridine; sodium hydroxide In dichloromethane; water

3-picoline-N-oxide (1003-73-2) + phosgene (75-44-5) + trimethyl-(5-methyl-pyridin-2-yl)-ammonium chloride → (5-methyl-pyridin-2-yl)amine (1603-41-4)

Conditions	Yield
With sodium hydroxide; hydrogen bromide; trimethylamine In ethyl acetate

diethyl (2-amino-5-methylpyridin-3-yl)phosphonate (1042146-82-6) → (5-methyl-pyridin-2-yl)amine (1603-41-4) + 2-amino-5-methyl-3-phosphanylpyridine (1244954-88-8)

Conditions	Yield
With lithium aluminium tetrahydride In diethyl ether at 0 - 20℃; for 48h;	A n/a B 59%

Upstream product

• 1003-73-2 3-picoline-N-oxide 
• 104712-04-1 2-nitroso-5-methyl-pyridine 
• 7757-82-6 sodium sulfate 
• 147151-28-8 2-dimethylamino-5-methylpyridine 
• 75-44-5 phosgene 
• 17282-00-7 3-bromo-5-methylpyridin-2-amine 
• 762-04-9 phosphonic acid diethyl ester 
• 36172-53-9 N,N-dimethyl-N′-(5-methylpyridin-2-yl)formimidamide 
• 110-86-1 pyridine 
• 407-25-0 trifluoroacetic anhydride 
• 5123-13-7 5,5-dimethyl-2-phenyl-1,3,2-dioxaborinane 
• 541544-19-8 C₁₀H₁₄N₂O 
• 100047-39-0 2-nitro-5-methylpyridine-N-oxide 
• 108-99-6 3-Methylpyridine 

Downstream Products

• 103649-94-1 3-hydroxy-6-hydroxymethyl-2-[α-(5-methyl-[2]pyridylamino)-benzyl]-pyran-4-one 
• 100974-08-1 N-(2,4-dimethyl-phenyl)-N'-(5-methyl-[2]pyridyl)-thiourea 
• 1026-26-2 N-(5-methyl-[2]pyridyl)-mandelamide 
• 41322-67-2 (5-methyl-pyridin-2-yl)-carbamic acid ethyl ester 
• 4931-47-9 N-(5-methylpyridin-2-yl)acetamide 
• 106475-60-9 N-(5-methyl-2-pyridyl)-N'-(p-tolyl)-thiourea 
• 53385-89-0 N-2-(5-picolyl)-N'-4-chlorophenylthiourea 
• 104997-08-2 N-(5-methyl-[2]pyridyl)-benzenesulfonamide 
• 100714-56-5 N-2-(5-picolylamino)-N'-(4-methoxyphenyl)thiourea 
• 2267-92-7 N-(4-fluoro-phenyl)-N'-(5-methyl-[2]pyridyl)-thiourea 
• 100973-55-5 N-(4-ethoxy-phenyl)-N'-(5-methyl-[2]pyridyl)-thiourea 
• 333442-17-4 N-acetyl-sulfanilic acid-(5-methyl-[2]pyridylamide) 
• 100280-44-2 N-(4-bromo-phenyl)-N'-(5-methyl-[2]pyridyl)-thiourea 
• 19056-89-4 diethyl 2-(((5-methylpyridin-2-yl)amino)methylene)malonate 

Relevant academic research and scientific papers

Mild, General, and Regioselective Synthesis of 2-Aminopyridines from Pyridine N -Oxides via N -(2-Pyridyl)pyridinium Salts

A synthesis of 2-aminopyridines from pyridine N-oxides via their corresponding N-(2-pyridyl)pyridinium salts has been demonstrated and investigated. The reaction sequence features a highly regioselective conversion of the N-oxide into its pyridinium salt

Ligand compound for copper catalyzed aryl halide coupling reaction, catalytic system and coupling reaction

The invention provides a ligand compound capable of being used for copper catalyzed aryl halide coupling reaction, the ligand compound is a three-class compound containing a 2-(substituted or non-substituted) aminopyridine nitrogen-oxygen group, and the invention also provides a catalytic system for the aryl halide coupling reaction. Thecatalytic system comprises a copper catalyst, a compound containing a 2-(substituted or non-substituted) aminopyridine nitrogen-oxygen group adopted as a ligand, alkali and a solvent, and meanwhile, the invention also provides a system for the aryl halide coupling reaction adopting the catalyst system. The compound containing the 2-(substituted or non-substituted) aminopyridine nitrogen oxygen group can be used as the ligand for the copper catalyzed aryl chloride coupling reaction, and the ligand is stable under a strong alkaline condition and can well maintain catalytic activity when being used for the copper-catalyzed aryl chloride coupling reaction. In addition, the copper catalyst adopting the compound as the ligand can particularly effectively promote coupling of copper catalyzed aryl chloride and various nucleophilic reagents which are difficult to generate under conventional conditions, C-N, C-O and C-S bonds are generated, and numerous useful small molecule compounds are synthesized. Therefore, the aryl halide coupling reaction has a very good large-scale application prospect by adopting the copper catalysis system of the ligand.

Ruthenium-Catalyzed Reductive Arylation of N-(2-Pyridinyl)amides with Isopropanol and Arylboronate Esters

A new three-component reductive arylation of amides with stable reactants (iPrOH and arylboronate esters), making use of a 2-pyridinyl (Py) directing group, is described. The N-Py-amide substrates are readily prepared from carboxylic acids and PyNH2, and the resulting N-Py-1-arylalkanamine reaction products are easily transformed into the corresponding chlorides by substitution of the HN-Py group with HCl. The 1-aryl-1-chloroalkane products allow substitution and cross-coupling reactions. Therefore, a general protocol for the transformation of carboxylic acids into a variety of functionalities is obtained. The Py-NH2 by-product can be recycled.

Method for preparing 2-amino-5-methylpyridine through ammoniation of 3-methylpyridine

The invention discloses a method for preparing 2-amino-5-methylpyridine through ammoniation of 3-methylpyridine. The method comprises the following steps: placing a solvent, metallic sodium, a catalyst, an additive and the raw material 3-methylpyridine in a high-pressure reaction container, carrying out heating to 50 to 80 DEG C, then slowly adding liquefied ammonia and carrying out pressurization for a reaction; continuing pressurization to 3 to 6 MPa and heating to 150 to 190 DEG C and continuing the reaction; and terminating the reaction until no obvious pressure increase occurs during the reaction. According to the invention, a one-pot process is employed, and hydrolysis, liquid separation and rectification are successively carried out so as to produce 2-amino-5-methylpyridine and byproduce 2-amino-3-methylpyridine, wherein a ratio of 2-amino-5-methylpyridine to 2-amino-3-methylpyridine is in a range of (9-20): 1. The method has a high 3-methylpyridine conversion rate; the selectivity of the obtained 2-amino-5-methylpyridine can reach 90% or above; and the yield of 2-amino-5-methylpyridine can be increased to 84.5% or above.

Synthetic method of 2-amino-5-methyl pyridine

The invention provides a synthetic method of 2-amino-5-methyl pyridine and relates to the field of research and development of chemical synthesis of drugs. The synthetic method comprises the following steps: adding methyl groups to pyridine to prepare 5-methyl pyridine; preparing N-oxidative methyl pyridine by 5-methyl pyridine; preparing 2-nitro-5-methyl nitrogen-oxidative pyridine by nitrogen-oxidative pyridine; and preparing the 2-amino-5-methyl pyridine by the 2-nitro-5-methyl nitrogen-oxidative pyridine. The synthetic method provided by the invention has the advantages of high product yield and purity, low in production cost and good in environment-friendly effect.

PROCESS FOR THE CATALYTIC DIRECTED CLEAVAGE OF AMIDE-CONTAINING COMPOUNDS

The present invention relates to a catalytic method for the conversion of amide-containing compouds by means of a build-in directing group and upon the action of a heteronucleophilic compound (in se an amine (RNH2 or RNHR') or an alcohol (ROH) or a thiol (RSH)) in the presence of a metal catalyst to respectively esters, thioesters, carbonates, thiocarbonates and to what is defined as amide-containing compounds (such as carboxamides, urea, carbamates, thiocarbamates). The present invention also relates to these amide-containing compounds having a build-in directing group (DG), as well as the use of such directing groups in the catalytic directed cleavage of N-DG amides with the use of heteronucleophiles (in se an amine (RNH2 or RNHR') or an alcohol (ROH) or thiol (RSH)).

Synthetic method of 4-(chloromethyl)-2-(3-(trifluoromethyl)phenoxy)pyridine

The invention relates to a synthetic method of 4-(chloromethyl)-2-(3-(trifluoromethyl)phenoxy)pyridine and belongs to the field of chemical synthesis.A traditional technology for producing 4-(chloromethyl)-2-(3-(trifluoromethyl)phenoxy)pyridine is backward, long in process, low in yield and large in three-waste amount and treatment is difficult.The synthetic method of the 4-(chloromethyl)-2-(3-(trifluoromethyl)phenoxy)pyridine is mild in reaction condition and high in yield.

Tertiary formylated amines by microwave irradiation of N,N-dimethyl- N′-(2-pyridyl) formamidines with methyl vinyl ketone

Treatment of N,N-dimethyl-N′-(2-pyridyl)formamidine with methyl vinyl ketone under microwave irradiation yields N-formyl-N-(3-oxobutyl)-2- pyridylamine without decomposition or polymerization of methyl vinyl ketone. The result is an alternative non-oxidat

Mild and highly selective palladium-catalyzed monoarylation of ammonia enabled by the use of bulky biarylphosphine ligands and palladacycle precatalysts

A method for the Pd-catalyzed arylation of ammonia with a wide range of aryl and heteroaryl halides, including challenging five-membered heterocyclic substrates, is described. Excellent selectivity for monoarylation of ammonia to primary arylamines was achieved under mild conditions or at rt by the use of bulky biarylphosphine ligands (L6, L7, and L4) as well as their corresponding aminobiphenyl palladacycle precatalysts (3a, 3b, and 3c). As this process requires neither the use of a glovebox nor high pressures of ammonia, it should be widely applicable.

Homogenous bimetallic catalysis on amination of ArX and ArX2 in aqueous medium-synergistic effect of dicopper complexes

A dicopper complex [Cu2(bpnp)(OH)(CF3COO) 3] (1) (bpnp = 2,7-bis(pyridin-2-yl)-l,8-naphthyridine) was found to be an excellent catalyst on amination of aryl halides and aryl dihalides with ammonia in aqueous solutions leading to the corresponding anilines and aryldiamines, respectively. Catalytic activity of 1 toward amination appears to be superior to those of other mono nuclear copper complexes. Furthermore, the bimetallic catalyst 1 gave exclusively diamination product in the reaction of ArX2 with ammonia, but other copper complexes showed poor selectivity. Kinetic product distribution study suggests that the dicopper metal ions in this catalysis promote the second amination efficiently.