183610-70-0

Basic information

• Product Name: 2-Amino-3-(trifluoromethyl)pyridine
• Synonyms: 3-(TRIFLUOROMETHYL)-2-PYRIDINAMINE;3-TRIFLUOROMETHYL-PYRIDIN-2-YLAMINE;2-AMINO-3-(TRIFLUOROMETHYL)PYRIDINE;3-(Trifluoromethyl)pyridin-2-amine;3-(TrifluoroMethyl)1-2-pyridinaMine;3-(TrifluoroMethyl)-2-pyridiMine;2-PyridinaMine, 3-(trifluoroMethyl)-;3-(Trifluoromethyl)pyridin-2-amine, 2-Amino-alpha,alpha,alpha-trifluoro-3-picoline
• CAS NO: 183610-70-0
• Molecular Formula: C₆H₅F₃N₂
• Molecular Weight: 162.11
• Product Categories: Amines and Anilines;Heterocycles;Pyridines, Pyrimidines, Purines and Pteredines;Amines;Pyridines;Fluorine series
• Mol File: 183610-70-0.mol

Chemical Properties

• Melting Point: 70-72°C
• Boiling Point: 203.2 °C at 760 mmHg
• Flash Point: 76.7 °C
• Appearance: /
• Density: 1.368 g/cm³
• Vapor Pressure: 0.28mmHg at 25°C
• Refractive Index: 1.478
• Storage Temp.: Room temperature.
• PKA: 4.18±0.36(Predicted)
• CAS DataBase Reference: 2-Amino-3-(trifluoromethyl)pyridine(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Amino-3-(trifluoromethyl)pyridine(183610-70-0)
• EPA Substance Registry System: 2-Amino-3-(trifluoromethyl)pyridine(183610-70-0)

Safety Data

• Hazard Codes: Xi,T
• Statements: 25-36-43
• Safety Statements: 26-36/37/39
• RIDADR: 2811
• WGK Germany: 3
• HazardClass: IRRITANT
• PackingGroup: Ⅲ
• Hazardous Substances Data: 183610-70-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
2-Amino-3-(trifluoromethyl)pyridine is used as a reagent for the preparation of novel propanamide derivatives, which function as fatty acid amide inhibitors. These derivatives have potential applications in the development of drugs targeting various medical conditions, such as pain management, inflammation, and neurological disorders.
In the context of the provided materials, 2-Amino-3-(trifluoromethyl)pyridine serves as a key intermediate in the synthesis of biologically active compounds, particularly those with potential therapeutic applications in the pharmaceutical industry. Its unique structure and reactivity make it a valuable component in the development of new drugs and therapeutic agents.

InChI:InChI=1/C6H5F3N2/c7-6(8,9)4-2-1-3-11-5(4)10/h1-3H,(H2,10,11)

Synthetic route

2-fluoro-3-trifluoromethylpyridine (65753-52-8) → 2-amino-3-trifluoromethylpyridine (183610-70-0)

Conditions	Yield
With ammonia In water at 130℃; under 22502.3 Torr; for 10h; Temperature;	95%

(4-methoxy-benzyl)-(3-trifluoromethyl-pyridin-2-yl)-amine (911112-72-6) → 2-amino-3-trifluoromethylpyridine (183610-70-0)

Conditions	Yield
Stage #1: (4-methoxy-benzyl)-(3-trifluoromethyl-pyridin-2-yl)-amine With sulfuric acid at 5 - 23℃; for 0.5h; Stage #2: With sodium hydroxide In water at 0℃;	92%

2-chloro-3-trifluoromethyl-pyridine (65753-47-1) → 2-amino-3-trifluoromethylpyridine (183610-70-0)

Conditions	Yield
With ammonia In water at 175℃; for 24h;	71%
With ammonia In water at 175℃; for 72h;
Multi-step reaction with 2 steps 1: hydrogen fluoride / 48 h / 130 °C / 60006 Torr / Autoclave 2: ammonia / water / 10 h / 130 °C / 22502.3 Torr View Scheme

methanol (67-56-1) + 8-Trifluoromethyl-tetrazolo[1,5-a]pyridine (143812-76-4) → 2-amino-3-trifluoromethylpyridine (183610-70-0) + 2-methoxy-4-trifluoromethyl-1H-1,3-diazepine (177211-80-2)

Conditions	Yield
In 1,4-dioxane at 25℃; for 1.33333h; Irradiation;	A 5% B 47%

2-amino-3-trifluoromethylpyridine (183610-70-0) → 5-bromo-3-(trifluoromethyl)pyridin-2-amine (79456-34-1)

Conditions	Yield
With N-Bromosuccinimide In acetonitrile at 0 - 20℃;	99%
With N-Bromosuccinimide In acetonitrile at 5 - 23℃; for 1h;	98%
With N-Bromosuccinimide In acetonitrile at 20℃;	93%

2-amino-3-trifluoromethylpyridine (183610-70-0) → 5-iodo-3-(trifluoromethyl)pyridin-2-amine

Conditions	Yield
With N-iodo-succinimide; acetic acid at 0 - 20℃; for 90h;	89%
Stage #1: 2-amino-3-trifluoromethylpyridine With N-iodo-succinimide; acetic acid at 0 - 20℃; Stage #2: With sodium hydrogencarbonate In water Cooling with ice;	76%
With N-iodo-succinimide	76%
With N-iodo-succinimide In acetic acid at 0 - 20℃;	76%
With N-iodo-succinimide In N,N-dimethyl-formamide at 20℃;	70%

2-amino-3-trifluoromethylpyridine (183610-70-0) → 5-chloro-3-(trifluoromethyl)pyridin-2-amine (79456-33-0)

Conditions	Yield
With N-chloro-succinimide In N,N-dimethyl-formamide at 60℃; for 1h;	88%
With N-chloro-succinimide In N,N-dimethyl-formamide at 60℃; for 1h;	88%
With N-chloro-succinimide In N,N-dimethyl-formamide at 60℃; for 1h; Inert atmosphere;

cyclohexanone (108-94-1) + 2-amino-3-trifluoromethylpyridine (183610-70-0) → 4-(trifluoromethyl)benzo[4,5]imidazo[1,2-a]pyridine

Conditions	Yield
With iodine; oxygen In 1,1,2,2-tetrachloroethane at 160℃; for 24h; Green chemistry;	88%

2-amino-3-trifluoromethylpyridine (183610-70-0) → C6H5F3N2O

Conditions	Yield
With 3-chloro-benzenecarboperoxoic acid In acetone at 0 - 20℃; for 12.5h;	81%

2-amino-3-trifluoromethylpyridine (183610-70-0) → 5-nitro-3-(trifluoromethyl)pyridin-2-amine (1121056-94-7)

Conditions	Yield
With sulfuric acid; nitric acid In water at 0 - 50℃; for 3.25h;	75%

2-chloro-5-(1-chloroethyl)pyridine + 2-amino-3-trifluoromethylpyridine (183610-70-0) → 1-[1-(6-chloro-3-pyridyl)ethyl]-3-(trifluoromethyl)pyridin-2-imine

Conditions	Yield
With sodium iodide In acetonitrile at 82℃; for 72h;	75%

1-Bromo-2-butanone (816-40-0) + 2-amino-3-trifluoromethylpyridine (183610-70-0) → 2-ethyl-8-(trifluoromethyl)imidazo[1,2-a]pyridine (1167570-72-0)

Conditions	Yield
With sodium hydrogencarbonate; sodium iodide In ethanol Heating / reflux;	74%

methyl 3-bromo-2-oxopropanoate (7425-63-0) + 2-amino-3-trifluoromethylpyridine (183610-70-0) → 8-trifluoromethyl-imidazo[1,2-a]pyridine-2-carboxylic acid methyl ester (1206972-73-7)

Conditions	Yield
In N,N-dimethyl-formamide at 60℃; for 3h;	72%

2-amino-3-trifluoromethylpyridine (183610-70-0) → 3-(trifluoromethyl)pyridine-2-(1H)-one (22245-83-6)

Conditions	Yield
With sulfuric acid; sodium nitrite In water at 70℃; for 1h;	69%

methyl 3-hydroxy-2-methylidene-3-phenylpropionate (18020-59-2) + 2-amino-3-trifluoromethylpyridine (183610-70-0) → 3-(benzyl)-9-(trifluoromethyl)-2H-pyrido[1,2-a]pyrimidin-2-one

Conditions	Yield
With 1,1,1,3',3',3'-hexafluoro-propanol Reflux;	67%

cyclohexanone (108-94-1) + 2-amino-3-trifluoromethylpyridine (183610-70-0) → 4-(trifluoromethyl)-6,7,8,9-tetrahydrobenzo[4,5]imidazo[1,2-a]pyridine

Conditions	Yield
With sulfur In neat (no solvent) at 110℃; for 16h; Inert atmosphere; regioselective reaction;	65%

1-(3-(methoxymethoxy)phenyl)prop-2-yn-1-yl acetate + 2-amino-3-trifluoromethylpyridine (183610-70-0) → 3-(3-(methoxymethoxy)phenyl)-2-methyl-8-(trifluoromethyl)imidazo[1,2-a]pyridine

Conditions	Yield
With copper acetylacetonate; N-ethyl-N,N-diisopropylamine; 2,6-bis(4,5-dihydrooxazol-2-yl)pyridine In methanol at 20℃; for 6h; Inert atmosphere; regioselective reaction;	61%

2-(4-((2-(trifluoromethyl)pyridin-4-yl)amino)phenyl)propanoic acid (1210909-06-0) + 2-amino-3-trifluoromethylpyridine (183610-70-0) → N-(3-(trifluoromethyl)pyridin-2-yl)-2-(4-((2-(trifluoromethyl)pyridin-4-yl)amino)phenyl)propanamide

Conditions	Yield
Stage #1: 2-(4-((2-(trifluoromethyl)pyridin-4-yl)amino)phenyl)propanoic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In acetonitrile at 20℃; for 0.5h; Stage #2: 2-amino-3-trifluoromethylpyridine In acetonitrile at 20℃;	59%

ibuprofen (15687-27-1) + 2-amino-3-trifluoromethylpyridine (183610-70-0) → 2-(4-isobutylphenyl)-N-(3-(trifluoromethyl)pyridin-2-yl)propanamide

Conditions	Yield
Stage #1: ibuprofen With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In acetonitrile at 20℃; for 0.5h; Stage #2: 2-amino-3-trifluoromethylpyridine In acetonitrile at 20℃; for 36h;	59%

tert-butyl 4-(10-bromo-2-oxo-1,2-dihydropyrimido[1,2-b]indazol-4-yl)piperidine-1-carboxylate + 2-amino-3-trifluoromethylpyridine (183610-70-0) → tert-butyl 4-(2-oxo-10-{[3-(trifluoromethyl)pyridin-2-yl]amino}-1,2-dihydropyrimido[1,2-b]indazol-4-yl)piperidine-1-carboxylate

Conditions	Yield
With potassium phosphate; t-BuBrettPhos; [(2-di-tert-butylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1’-biphenyl)-2-(2’-amino-1,1‘-biphenyl)]palladium(II) methanesulfonate In tert-butyl alcohol at 110℃; Inert atmosphere;	58%

3-methoxyphenylglyoxal (32025-65-3) + 2-amino-3-trifluoromethylpyridine (183610-70-0) → 2-chloro-3-(3-methoxyphenyl)-8-(trifluoromethyl)imidazo[1,2-a]pyridine (1167571-66-5)

Conditions	Yield
Stage #1: 3-methoxyphenylglyoxal; 2-amino-3-trifluoromethylpyridine In dichloromethane for 1h; Heating / reflux; Stage #2: With thionyl chloride In tetrachloromethane for 0.5h; Heating / reflux; Stage #3: With potassium carbonate In water	56%

methyl 2-hydroxymethylacrylate (15484-46-5) + 2-amino-3-trifluoromethylpyridine (183610-70-0) → 3-methyl-9-(trifluoromethyl)-2H-pyrido[1,2-a]pyrimidin-2-one

Conditions	Yield
With 1,1,1,3',3',3'-hexafluoro-propanol Reflux;	52%

chloroacetone (78-95-5) + 2-amino-3-trifluoromethylpyridine (183610-70-0) → 2-methyl-8-(trifluoromethyl)imidazo[1,2-a]pyridine (1167570-71-9)

Conditions	Yield
With sodium hydrogencarbonate; sodium iodide In ethanol Heating / reflux;	51%

1-phenylprop-2-ynyl acetate (16169-88-3, 84681-19-6, 116119-86-9, 116182-55-9) + 2-amino-3-trifluoromethylpyridine (183610-70-0) → 2-methyl-3-phenyl-8-(trifluoromethyl)imidazo[1,2-a]pyridine

Conditions	Yield
With copper acetylacetonate; N-ethyl-N,N-diisopropylamine; 2,6-bis(4,5-dihydrooxazol-2-yl)pyridine In methanol at 20℃; for 18h; Inert atmosphere; regioselective reaction;	50%

N-((3-bromo-5-methylphenyl)sulfonyl)-2-(naphthalen-2-yloxy)acetamide + 2-amino-3-trifluoromethylpyridine (183610-70-0) → N-((3-methyl-5-((3-(trifluoromethyl)pyridin-2-yl)amino)-phenyl)sulfonyl)-2-(naphthalen-2-yloxy)acetamide

Conditions	Yield
With palladium diacetate; caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene In 1,4-dioxane at 100℃; Inert atmosphere;	50%

fluorobiprofen (5104-49-4) + 2-amino-3-trifluoromethylpyridine (183610-70-0) → 2-(2-fluoro-(1,1'-biphenyl)-4-yl)-N-(3-(trifluoromethyl)pyridin-2-yl)propanamide

Conditions	Yield
Stage #1: fluorobiprofen With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In acetonitrile at 20℃; for 0.5h; Stage #2: 2-amino-3-trifluoromethylpyridine In acetonitrile at 20℃; for 72h;	45%

phenylacetaldehyde (122-78-1) + 2-amino-3-trifluoromethylpyridine (183610-70-0) → 3-phenyl-8-(trifluoromethyl)imidazo[1,2-a]pyridine

Conditions	Yield
With sulfur In cyclohexane; dimethyl sulfoxide at 120℃; for 1h; Sealed tube;	41%

2-(6-chloro-carbazol-2-yl)-propionic acid (53716-49-7) + 2-amino-3-trifluoromethylpyridine (183610-70-0) → 2-(6-chloro-9H-carbazol-2-yl)-N-(3-(trifluoromethyl)pyridin-2-yl)propanamide

Conditions	Yield
Stage #1: 2-(6-chloro-carbazol-2-yl)-propionic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In acetonitrile at 20℃; for 0.5h; Stage #2: 2-amino-3-trifluoromethylpyridine In acetonitrile at 20℃; for 36h;	41%

2-chloropyrazin (14508-49-7) + 2-amino-3-trifluoromethylpyridine (183610-70-0) → C10H7F3N4

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 90℃; for 40h; Inert atmosphere;	29%

Upstream product

• 67-56-1 methanol 
• 143812-76-4 8-Trifluoromethyl-tetrazolo[1,5-a]pyridine 
• 65753-47-1 2-chloro-3-trifluoromethyl-pyridine 
• 911112-72-6 (4-methoxy-benzyl)-(3-trifluoromethyl-pyridin-2-yl)-amine 
• 65753-52-8 2-fluoro-3-trifluoromethylpyridine 

Downstream Products

• 22245-83-6 3-(trifluoromethyl)pyridine-2-(1H)-one 
• 104040-74-6 3-trifluoromethylpyridine-2(1H)-thione 
• 79456-34-1 5-bromo-3-(trifluoromethyl)pyridin-2-amine 
• 1121056-94-7 5-nitro-3-(trifluoromethyl)pyridin-2-amine 
• 1167571-66-5 2-chloro-3-(3-methoxyphenyl)-8-(trifluoromethyl)imidazo[1,2-a]pyridine 
• 911112-05-5 5-iodo-3-(trifluoromethyl)pyridin-2-amine 
• 1208362-08-6 2-phenyl-8-(trifluoromethyl)imidazo[1,2-a]pyridine 
• 1206972-73-7 8-trifluoromethyl-imidazo[1,2-a]pyridine-2-carboxylic acid methyl ester 
• 79456-33-0 5-chloro-3-(trifluoromethyl)pyridin-2-amine 
• 1284244-27-4 4-{[6-bromo-3-chloro-8-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]carbonyl}-1-(4,4-difluorocyclohexyl)-2-piperazinone 
• 1284244-29-6 4-{[3-chloro-6-cyclopropyl-8-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]carbonyl}-1-(4-oxocyclohexyl)-2-piperazinone 
• 1284244-33-2 4-{[6-bromo-3-chloro-8-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]carbonyl}-1-(4-oxocyclohexyl)-2-piperazinone 
• 1284243-02-2 4-{[3-chloro-6-(1H-pyrazol-4-yl)-8-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]carbonyl}-1-phenyl-2-piperazinone 
• 1284245-44-8 4-{[3-chloro-6-propyl-8-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]carbonyl}-1-cyclohexyl-2-piperazinone 

Relevant articles and documents

Synthesis method and applications of polysubstituted 2-aminopyridine derivative

The invention belongs to the field of organic synthetic chemistry, and relates to a synthetic method and applications of a polysubstituted 2-aminopyridine derivative. According to the method, a 1,2,3-triazine compound and a cyanomethyl compound are used as substrates and are subjected to a one-step cycloaddition reaction under an alkaline condition to obtain a polysubstituted 2-aminopyridine derivative, wherein the reaction does not involve in danger and control reagents and medicines, and a simple, safe, efficient and environment-friendly strategy is provided for synthesizing the polysubstituted 2-aminopyridine derivative. According to the present invention, the obtained product is subjected to further derivatization, such that the active molecule or the drug molecule containing the 2-aminopyridine structure can be synthesized, such as active molecule SC-53606, drug molecule apatinib and nevirapine.

Preparation method of 2-hydroxyl-3-trifluoromethylpyridine

The invention relates to the technical field of chemical synthesis, and particularly discloses a preparation method of 2-hydroxyl-3-trifluoromethylpyridine. According to the preparation method disclosed by the invention, by using the 2-chloro-3-trifluoromethylpyridine as a starting raw material, fluorination is carried out under a certain condition so that 2-fluro-3-trifluoromethylpyridine is prepared; ammonolysis reaction is carried out on the 2-fluro-3-trifluoromethylpyridine so as to prepare 2-amino-3-trifluoromethylpyridine; then diazotization reaction is carried out to obtain the 2-hydroxyl-3-trifluoromethylpyridine. The preparation method disclosed by the invention is reliable in process, raw materials are sufficient and easy to get in the market, the production cost is low, an operation is simple, the yield is high, and scale production is facilitated; at present, a preparation method of the same or other components is never seen at home and abroad.

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)).

Novel compounds as metabotropic glutamate receptor antagonists

The present invention relates to compounds of formula (I) wherein A, E G, J, L, M, R1, R2, and R3 are as defined in the specification and claims. The invention also relates to pharmaceutical compositions containing such compounds and methods for preparing the compounds and compositions. The compounds are metabotropic glutamate receptor antagonists and are useful for the treatment of a variety of CNS disorders.

NOVEL SUBSTITUTED IMIDAZOLE DERIVATIVES

The present invention relates to a compound represented by Formula [I] or a pharmaceutically acceptable salt or ester thereof: wherein: X1, X2, X3, and X4, which may be identical or different, are each C or N, provided that none to two of X1, X2, X3, and X4 is/are N; Y is CH or N; R1, R1', R2, R2', R3, R3', R4, and R4', which may be identical or different, are each a hydrogen atom, a lower alkyl group, or the like; R5 is a hydrogen atom or a methyl group; R6 and R7, which may be identical or different, are each a hydrogen atom, a lower alkyl group, or the like; R8 and R8', which may be identical or different, are each a hydrogen atom, a lower alkyl group, or the like; R9 is an aryl group or a heteroaryl group which may be substituted; and n is an integer from 1 to 3, and a PLK1 inhibitor or an anticancer agent containing the same.

Nucleophilic displacement in 2-chloro(trifluoromethyl)pyridines with amines and ammonia

The activating effect of trifluoromethyl groups in 2-chloro(trifluoromethyl)pyridines was investigated by comparing reactions of these compounds and of 2-chloropyridine with secondary cyclic amines. The ammonolysis of 2-chloro-3-trifluoromethylpyridine and 2-chloro-4-trifluoromethylpyridine is also reported and shown to proceed, in contrast to the reported behaviour of 2-chloro-5-trifluoromethylpyridine, without hydrolysis of the trifluoromethyl function. Both 2-amino-3-trifluoromethylpyridine and 2-amino-4-trifluoromethylpyridine were converted (via the corresponding pyridones) to 3-trifluoromethylpyridin-2(1H)-thione and 4-trifluoromethylpyridin-2(1H)-thione, and a number of S-alkyl derivatives of the latter compounds were prepared.

Synthesis of 1H- and 5H-1,3-diazepines from azido- and tetrazolo-pyridines

Stable 1H-1,3-diazepines 7-9, 10, 13, 14, 17 and 19 are obtained, often in high yields, by photolysis of trifluoromethyl-substituted azido- or tetrazolo-pyridines in the presence of alcohols or amines; in some cases, 5H-1,3-diazepines are also formed (11, 21 and 23).