133627-45-9

Basic information

• Product Name: 3-Amino-2-chloro-4-methylpyridine
• Synonyms: 2-CHLORO-4-METHYL-PYRIDIN-3-YLAMINE;2-CHLORO-4-METHYLPYRIDIN-3-AMINE;2-CHLORO-3-AMINO-4-PICOLINE;2-CHLORO-3-AMINO-4-METHYLPYRIDINE;3-AMINO-2-CHLORO-4-METHYLPYRIDINE;3-AMINO-2-CHLORO-4-PICOLINE;ASINEX-REAG BAS 13794917;TIMTEC-BB SBB010194
• CAS NO: 133627-45-9
• Molecular Formula: C6H7ClN2
• Molecular Weight: 142.59
• EINECS: -0
• Product Categories: PYRIDINE;Amines and Anilines;Heterocycles;Pyridines, Pyrimidines, Purines and Pteredines;pharmacetical;Amines;Pyridines;Heterocyclic Compounds;(intermediate of nevirapine);Aromatics Compounds;Chloropyridines;Halopyridines;Aromatics;Bases & Related Reagents;Nucleotides;Building Blocks;C5 to C6;C6;Chemical Synthesis;Halogenated Heterocycles;Heterocyclic Building Blocks;API Intermediate
• Mol File: 133627-45-9.mol
• Article Data: 31

Chemical Properties

• Melting Point: 61-64°C
• Boiling Point: 283.3 °C at 760 mmHg
• Flash Point: 125.2 °C
• Appearance: off white crystals
• Density: 1.26 g/cm³
• Vapor Pressure: 0.0229mmHg at 25°C
• Refractive Index: 1.592
• Storage Temp.: Room temperature.
• Solubility: Chloroform, Ethanol
• PKA: 3.22±0.10(Predicted)
• CAS DataBase Reference: 3-Amino-2-chloro-4-methylpyridine(CAS DataBase Reference)
• NIST Chemistry Reference: 3-Amino-2-chloro-4-methylpyridine(133627-45-9)
• EPA Substance Registry System: 3-Amino-2-chloro-4-methylpyridine(133627-45-9)

Safety Data

• Hazard Codes: Xi,Xn
• Statements: 36/37/38-41-37/38-22
• Safety Statements: 26-36/37/39-36-39
• RIDADR: UN2811
• WGK Germany: 3
• HazardClass: 6.1
• PackingGroup: III
• Hazardous Substances Data: 133627-45-9(Hazardous Substances Data)

Usage

Chemical Properties

Off White Crystals

InChI:InChI=1/C6H7ClN2/c1-4-6(7)5(8)2-3-9-4/h2-3H,1H3,(H2,8,9)

Synthetic route

2-chloro-3-nitro-4-methylpyridine (23056-39-5) → 3-Amino-2-chloro-4-methylpyridine (133627-45-9)

Conditions	Yield
With hydrogenchloride; tin(ll) chloride In diethyl ether for 0.333333h; Ambient temperature;	98%
Stage #1: 2-chloro-3-nitro-4-methylpyridine With iron; acetic acid at 70 - 80℃; Stage #2: With sodium carbonate In water pH=8.0 - 8.5; Product distribution / selectivity;	90.79%
Stage #1: 2-chloro-3-nitro-4-methylpyridine With hydrogenchloride In methanol; water at 65℃; Stage #2: With iron In methanol; water at 65℃; Product distribution / selectivity;	90.1%

2-chloro-4-methyl-3-pyridinecarboxamide (152362-01-1) → 3-Amino-2-chloro-4-methylpyridine (133627-45-9)

Conditions	Yield
With sodium hypobromide; bromine; sodium hydroxide In water at 65 - 75℃; for 4h; Hofmann Rearrangement;	98%
With bromine; sodium hydroxide In water at 0 - 20℃; for 2h;	97%
With bromine; sodium hydroxide In water; toluene at 0 - 60℃;	96.9%

4-methylpiperidin-3-one → 3-Amino-2-chloro-4-methylpyridine (133627-45-9)

Conditions	Yield
Stage #1: 4-methylpiperidin-3-one With hydrogenchloride; dihydrogen peroxide In chloroform; water at 30 - 40℃; for 5h; Green chemistry; Stage #2: With ammonium hydroxide at 40 - 45℃; for 3h; Solvent; Reagent/catalyst; Green chemistry;	93.3%

3-amino-4-methylpyridine (3430-27-1) → 3-Amino-2-chloro-4-methylpyridine (133627-45-9)

Conditions	Yield
With hydrogenchloride; dihydrogen peroxide at 20℃; for 0.5h;	89%
With hydrogenchloride; chlorine In water at 20℃; for 0.416667h;	84%
Stage #1: 3-amino-4-methylpyridine With hydrogenchloride In water at 40℃; Cooling with ice; Stage #2: With dihydrogen peroxide for 2h;	83.2%

3-nitro-4-methylpyridine (5832-44-0) → 3-Amino-2-chloro-4-methylpyridine (133627-45-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 97 percent / H2 / 5 percent Pd/C / methanol / 5 h / 20 °C / 3750.3 Torr 2: 89 percent / conc. aq. HCl; 35 percent aq. H2O2 / 0.5 h / 20 °C View Scheme

2-chloro-4-methylnicotinoylchloride (50839-95-7) → 3-Amino-2-chloro-4-methylpyridine (133627-45-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: NH3(g) / toluene / below 30 deg C 2: 93 percent / NaOH, Br2 / H2O / 1.) 5 deg C; 2.) 75 deg C, 90 min View Scheme

ethyl 2-chloro-4-methyl-3-pyridinecarboxylate (50840-02-3) → 3-Amino-2-chloro-4-methylpyridine (133627-45-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: 90 percent / NaOH / methanol; H2O / 75 °C 2: SOCl2 / toluene / 1.) 70 deg C, 1 h; 2.) reflux, 4 h 3: NH3(g) / toluene / below 30 deg C 4: 93 percent / NaOH, Br2 / H2O / 1.) 5 deg C; 2.) 75 deg C, 90 min View Scheme

2-chloro-4-methyl-3-pyridinecarboxylic acid (142266-63-5) → 3-Amino-2-chloro-4-methylpyridine (133627-45-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: SOCl2 / toluene / 1.) 70 deg C, 1 h; 2.) reflux, 4 h 2: NH3(g) / toluene / below 30 deg C 3: 93 percent / NaOH, Br2 / H2O / 1.) 5 deg C; 2.) 75 deg C, 90 min View Scheme

ethyl 2-chloro-2-cyano-3-methyl-5-oxopentanoate (152362-00-0) → 3-Amino-2-chloro-4-methylpyridine (133627-45-9)

Conditions	Yield
Multi-step reaction with 5 steps 1: 17 percent / PCl3, HCl(g) / dimethylformamide / 1.) 85 deg C; 2.) 90 deg C 2: 90 percent / NaOH / methanol; H2O / 75 °C 3: SOCl2 / toluene / 1.) 70 deg C, 1 h; 2.) reflux, 4 h 4: NH3(g) / toluene / below 30 deg C 5: 93 percent / NaOH, Br2 / H2O / 1.) 5 deg C; 2.) 75 deg C, 90 min View Scheme

2-chloro-3-nitro-4-methylpyridine (23056-39-5) + tin(IV) chloride dihydrate → 3-Amino-2-chloro-4-methylpyridine (133627-45-9)

Conditions	Yield
With sodium hydroxide; acetic acid In hydrogenchloride; water

C9H14N2O3 → 3-Amino-2-chloro-4-methylpyridine (133627-45-9)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: sulfuric acid / ethanol / 3.67 h / 20 - 50 °C 2.1: trichlorophosphate / 2 h / 35 °C / Reflux 3.1: sulfuric acid / 4 h / 50 - 105 °C 3.2: 1.5 h / 60 - 65 °C 3.3: pH 7 / Cooling with ice 4.1: sodium hypochlorite; sodium hydroxide / methanol; water / 4 h / 10 - 60 °C View Scheme
Multi-step reaction with 3 steps 1.1: sulfuric acid / ethanol / 1.17 h / 25 - 50 °C 2.1: trichlorophosphate / 2.25 h / 35 °C / Reflux 2.2: 50 - 110 °C 3.1: sodium hydroxide; sodium hypochlorite / ethanol; water / 4.17 h / 10 - 60 °C View Scheme

2-hydroxy-4-methylpyridine-3-carbonitrile (93271-59-1) → 3-Amino-2-chloro-4-methylpyridine (133627-45-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: trichlorophosphate / 2 h / 35 °C / Reflux 2.1: sulfuric acid / 4 h / 50 - 105 °C 2.2: 1.5 h / 60 - 65 °C 2.3: pH 7 / Cooling with ice 3.1: sodium hypochlorite; sodium hydroxide / methanol; water / 4 h / 10 - 60 °C View Scheme

2-chloro-4-methyl-3-pyridinecarbonitrile (65169-38-2) → 3-Amino-2-chloro-4-methylpyridine (133627-45-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sulfuric acid / 4 h / 50 - 105 °C 1.2: 1.5 h / 60 - 65 °C 1.3: pH 7 / Cooling with ice 2.1: sodium hypochlorite; sodium hydroxide / methanol; water / 4 h / 10 - 60 °C View Scheme
Multi-step reaction with 2 steps 1.1: sulfuric acid / 1.25 h / 40 - 105 °C 1.2: 70 - 75 °C 2.1: sodium hydroxide; bromine / toluene; water / 0 - 60 °C View Scheme
Multi-step reaction with 2 steps 1: sulfuric acid / water / 8.25 h / 40 - 105 °C 2: sodium hydroxide; bromine / water / 2 h / 0 - 20 °C View Scheme

2-amino-4-methyl-3-nitropyridine (6635-86-5) → 3-Amino-2-chloro-4-methylpyridine (133627-45-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium nitrite; sulfuric acid / water 2: trichlorophosphate / 110 °C 3: tin(II) chloride dihdyrate; hydrogenchloride / 55 °C View Scheme
Multi-step reaction with 3 steps 1: sodium nitrite; sulfuric acid / 4 h / 20 °C 2: trichlorophosphate / 4 h / 110 °C 3: tin(II) chloride dihdyrate; hydrogenchloride / 1 h / 50 °C View Scheme

2-hydroxy-4-methyl-3-nitropyridine (21901-18-8) → 3-Amino-2-chloro-4-methylpyridine (133627-45-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: trichlorophosphate / 110 °C 2: tin(II) chloride dihdyrate; hydrogenchloride / 55 °C View Scheme
Multi-step reaction with 2 steps 1: trichlorophosphate / 4 h / 110 °C 2: tin(II) chloride dihdyrate; hydrogenchloride / 1 h / 50 °C View Scheme

2-(4-(dimethylamino)but-3-en-2-ylidene)malononitrile (71493-72-6) → 3-Amino-2-chloro-4-methylpyridine (133627-45-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: hydrogenchloride / 2 h / 50 - 55 °C 2.1: sulfuric acid / 1.25 h / 40 - 105 °C 2.2: 70 - 75 °C 3.1: sodium hydroxide; bromine / toluene; water / 0 - 60 °C View Scheme
Multi-step reaction with 3 steps 1: hydrogenchloride / toluene / 20 - 55 °C 2: sulfuric acid / water / 8.25 h / 40 - 105 °C 3: sodium hydroxide; bromine / water / 2 h / 0 - 20 °C View Scheme

isopropylidenemalonodinitrile (13166-10-4) → 3-Amino-2-chloro-4-methylpyridine (133627-45-9)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: triethylamine; acetic anhydride / toluene / 2 h / 5 - 20 °C / Inert atmosphere 2.1: hydrogenchloride / 2 h / 50 - 55 °C 3.1: sulfuric acid / 1.25 h / 40 - 105 °C 3.2: 70 - 75 °C 4.1: sodium hydroxide; bromine / toluene; water / 0 - 60 °C View Scheme
Multi-step reaction with 4 steps 1.1: acetic anhydride / toluene / 5 - 10 °C / Inert atmosphere 1.2: 2 h / 5 - 20 °C / Inert atmosphere 2.1: hydrogenchloride / toluene / 20 - 55 °C 3.1: sulfuric acid / water / 8.25 h / 40 - 105 °C 4.1: sodium hydroxide; bromine / water / 2 h / 0 - 20 °C View Scheme

picoline (108-89-4) → 3-Amino-2-chloro-4-methylpyridine (133627-45-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: aluminum (III) chloride; potassium bromide / 1 h / 20 °C / Inert atmosphere 1.2: 27 h / 120 °C / Inert atmosphere 2.1: copper(II) sulfate; ammonia / methanol / 8 h / 160 °C / 3800.26 Torr / Autoclave 3.1: hydrogenchloride / water / 40 °C / Cooling with ice 3.2: 2 h View Scheme

3-methyltetrahydro-2-furanone (1679-47-6) → 3-Amino-2-chloro-4-methylpyridine (133627-45-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / dichloromethane / 5 h / 40 - 45 °C / Green chemistry 1.2: 4 h / 20 - 25 °C / Green chemistry 1.3: 4 h / 30 - 35 °C / 1500.15 - 2250.23 Torr / Autoclave; Green chemistry 2.1: hydrogenchloride; dihydrogen peroxide / chloroform; water / 5 h / 30 - 40 °C / Green chemistry 2.2: 3 h / 40 - 45 °C / Green chemistry View Scheme

methyl 2-(cyclopropylamino)nicotinate + 3-Amino-2-chloro-4-methylpyridine (133627-45-9) → Nevirapine (129618-40-2)

Conditions	Yield
With sodium hydride In diethylene glycol dimethyl ether at 65 - 165℃; Flow reactor; Green chemistry;	96%
Multi-step reaction with 2 steps 1.1: sodium hydride / 3.5 h / 30 - 60 °C / Inert atmosphere 1.2: 2 h / 55 - 65 °C / Inert atmosphere 2.1: sodium hydride; diethylene glycol dimethyl ether / 2.5 h / 100 - 125 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1.1: sodium hydride / diethylene glycol dimethyl ether / 0.5 h / 20 °C 1.2: 2 h / 60 °C 2.1: sodium hydride / diethylene glycol dimethyl ether / 4 h / 105 - 117 °C / Green chemistry View Scheme

3-Amino-2-chloro-4-methylpyridine (133627-45-9) → 2-chloro-3-amino-4-methyl-6-bromopyridine (1038920-08-9)

Conditions	Yield
With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione In dichloromethane at 0 - 20℃; for 1.66667h; Product distribution / selectivity;	94%

methyl 2-(cyclopropylamino)nicotinate + 3-Amino-2-chloro-4-methylpyridine (133627-45-9) → N-(2-chloro-4-methyl-3-pyridinyl)-2-(cyclopropylamino)-3-pyridinecarboxamide (133627-47-1)

Conditions	Yield
Stage #1: 3-Amino-2-chloro-4-methylpyridine With sodium hydride In diethylene glycol dimethyl ether at 20℃; for 0.5h; Stage #2: methyl 2-(cyclopropylamino)nicotinate In diethylene glycol dimethyl ether at 60℃; for 2h; Reagent/catalyst;	94%

2-Chloronicotinoyl chloride (49609-84-9) + 3-Amino-2-chloro-4-methylpyridine (133627-45-9) → 2-chloro-N-(2-chloro-4-methyl-3-pyridinyl)-3-pyridinecarboxamide (133627-46-0)

Conditions	Yield
In dichloromethane 1.) -78 deg C, 1 h, 2.) RT, 23 h;	87%
With pyridine In 1,4-dioxane; cyclohexane for 48h; Ambient temperature;	65.5%
With potassium carbonate In ethyl acetate at 75 - 80℃; for 14h; Product distribution / selectivity;

ethyl 2-cyano-3,3-di(methylsulfanyl)acrylate (17823-58-4) + 3-Amino-2-chloro-4-methylpyridine (133627-45-9) → (E)-ethyl 3-(2-chloro-4-methylpyridin-3-yl-amino)-2-cyano-3-methylthioacrylate (868637-95-0)

Conditions	Yield
With sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide at 50℃; for 0.5h; microwave irradiation;	85.2%
With sodium hydride In N,N-dimethyl-formamide; toluene at 40 - 45℃; for 1h;	73.5%

3-Amino-2-chloro-4-methylpyridine (133627-45-9) + Cyclopropylamine (765-30-0) → N-(2-chloro-4-methyl-3-pyridinyl)-2-(cyclopropylamino)-3-pyridinecarboxamide (133627-47-1)

Conditions	Yield
In toluene at 125 - 130℃; under 775.743 Torr; for 21h;	79.64%

methanol (67-56-1) + 3-Amino-2-chloro-4-methylpyridine (133627-45-9) → 2-methoxy-3-amino-4-methylpyridine (76005-99-7)

Conditions	Yield
With copper(l) iodide; sodium at 110℃; for 14h; Autoclave;	78.7%
With copper(l) iodide; sodium at 110℃; for 14h; Autoclave;	78.7%

3-Amino-2-chloro-4-methylpyridine (133627-45-9) + 4,5-dichloro-1,2,3-dithiazolium chloride (75318-43-3) → (Z)-2-chloro-N-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)-4-methylpyridin-3-amine (1417816-45-5)

Conditions	Yield
Stage #1: 3-Amino-2-chloro-4-methylpyridine; 4,5-dichloro-1,2,3-dithiazolium chloride In dichloromethane at 20℃; for 1h; Stage #2: With 2,6-dimethylpyridine In dichloromethane at 20℃; for 2h;	60%
Stage #1: 3-Amino-2-chloro-4-methylpyridine; 4,5-dichloro-1,2,3-dithiazolium chloride In dichloromethane for 1h; Stage #2: With pyridine for 2h;	42%

3-Amino-2-chloro-4-methylpyridine (133627-45-9) → 2-chloro-3-iodo-4-methyl-pyridine (926922-28-3)

Conditions	Yield
Stage #1: 3-Amino-2-chloro-4-methylpyridine With hydrogenchloride; sodium nitrite In water at 0℃; Stage #2: With potassium iodide In water at 0 - 20℃;	58%
Stage #1: 3-Amino-2-chloro-4-methylpyridine With hydrogenchloride; sodium nitrite In water at 0℃; Stage #2: With potassium iodide In water at 0 - 20℃;	47%
Stage #1: 3-Amino-2-chloro-4-methylpyridine With hydrogenchloride; sodium nitrite In water at 0℃; for 1h; Stage #2: With potassium iodide In water at 0 - 20℃; for 12h;

2-Picolinic acid (98-98-6) + 3-Amino-2-chloro-4-methylpyridine (133627-45-9) → N-(2-chloro-4-methylpyridin-3-yl)picolinamide

Conditions	Yield
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine In N,N-dimethyl-formamide at 70℃; for 15h;	55%

2-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamido)acetic acid (1423020-38-5) + 3-Amino-2-chloro-4-methylpyridine (133627-45-9) → 3-bromo-N-(2-((2-chloro-4-methylpyridin-3-yl)amino)-2-oxoethyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide (1423020-32-9)

Conditions	Yield
With triethylamine; trichlorophosphate In acetonitrile for 2h; Reflux;	52.6%

3-Amino-2-chloro-4-methylpyridine (133627-45-9) → bis(3-amino-4-methyl-2-pyridyl) diselenide

Conditions	Yield
With selenium; sodium tetrahydroborate; toluene-4-sulfonic acid at 50℃; for 20h; Inert atmosphere;	51%

3-Amino-2-chloro-4-methylpyridine (133627-45-9) → 7-chloro-1H-pyrazolo<3,4-c>pyridine (76006-11-6)

Conditions	Yield
With potassium acetate; sodium nitrite In water; ethyl acetate	46%
Multi-step reaction with 2 steps 1: 2.1 g / toluene / 2 h / 100 °C 2: 1.) phosphorus pentaoxide, potassium acetate, nitrosyl chloride, 2.) sodium carbonate / 1.) acetic acid, 2.) benzene, reflux View Scheme
Multi-step reaction with 4 steps 1: 2.1 g / toluene / 2 h / 100 °C 2: 1.) phosphorus pentaoxide, potassium acetate, nitrosyl chloride, 2.) sodium carbonate / 1.) acetic acid, 2.) benzene, reflux 3: 67 percent / phosphorus pentasulphide / pyridine / 4.5 h / Heating 4: 71 percent / chlorine, conc. hydrochloric acid / 0.33 h View Scheme

6-chloropicolinic acid (4684-94-0) + 3-Amino-2-chloro-4-methylpyridine (133627-45-9) → 6-chloro-N-(2-chloro-4-methylpyridin-3-yl)picolinamide

Conditions	Yield
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine In N,N-dimethyl-formamide at 70℃; for 15h;	46%

isopropyl (S)-5-fluoro-6-(3-(fluoromethyl)-4-(3-hydroxypropyl)-5-oxo-4,5-dihydro-1H-1.2,4-triazol-1-yl)-2-((1,1,1-trifluoropropan-2-yl)oxy)nicotinate + 3-Amino-2-chloro-4-methylpyridine (133627-45-9) → N-(2-chloro-4-methyl-3-pyridyl)-5-fluoro-6-[3-(fluoromethyl)-4-(3-hydroxypropyl)-5-oxo-1,2,4-triazol-1-yl]-2-[(1S)-2,2,2-trifluoro-1-methylethoxy]pyridine-3-carboxamide

Conditions	Yield
With trimethylaluminum In dichloromethane at 50℃; for 12h;	40%

3-Amino-2-chloro-4-methylpyridine (133627-45-9) + (1-methyl-1H-pyrazol-5-yl)boronic acid (720702-41-0) → 4-methyl-2-(1-methyl-1H-pyrazol-5-yl)pyridin-3-amine

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate In 1,4-dioxane; water at 100℃; for 3h;	30%

3-Amino-2-chloro-4-methylpyridine (133627-45-9) + aniline (62-53-3) → 4-methyl-N2-phenylpyridine-2,3-diamine (1216164-90-7)

Conditions	Yield
at 180℃; for 1.25h; Microwave irradiation;	28%

2-(2,5-dichloro-phenoxy)-nicotinic acid (108464-34-2) + 3-Amino-2-chloro-4-methylpyridine (133627-45-9) + methyl iodide (74-88-4) → N-(2-chloro-4-methylpyridin-3-yl)-2-(2,5-dichlorophenoxy)-N-methylnicotinamide (1224638-77-0)

Conditions	Yield
Stage #1: 2-(2,5-dichloro-phenoxy)-nicotinic acid; 3-Amino-2-chloro-4-methylpyridine With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 18h; Stage #2: methyl iodide With sodium hydride In N,N-dimethyl-formamide; mineral oil at 40℃; for 2h;	3%

acetic anhydride (108-24-7) + 3-Amino-2-chloro-4-methylpyridine (133627-45-9) → 3-acetamido-2-chloro-4-methylpyridine (76006-00-3)

Conditions	Yield
In toluene at 100℃; for 2h;	2.1 g
In dichloromethane at 20℃;
In dichloromethane at 20℃; for 24h;

3-Amino-2-chloro-4-methylpyridine (133627-45-9) → (Z)-ethyl 3-(2-chloro-4-methylpyridin-3-ylamino)-2-cyano-3-isopropylaminoacrylate

Conditions	Yield
Multi-step reaction with 2 steps 1: 73.5 percent / sodium hydride / dimethylformamide; toluene / 1 h / 40 - 45 °C 2: 63.8 percent / ethanol / 4 h / 78 - 80 °C View Scheme

3-Amino-2-chloro-4-methylpyridine (133627-45-9) → (Z)-ethyl 3-(2-chloro-4-methylpyridin-3-ylamino)-3-propylamino-2-cyanoacrylate

Conditions	Yield
Multi-step reaction with 2 steps 1: 73.5 percent / sodium hydride / dimethylformamide; toluene / 1 h / 40 - 45 °C 2: 54.7 percent / ethanol / 4 h / 78 - 80 °C View Scheme

3-Amino-2-chloro-4-methylpyridine (133627-45-9) → (Z)-ethyl 3-butylamino-3-(2-chloro-4-methylpyridin-3-ylamino)-2-cyanoacrylate

Conditions	Yield
Multi-step reaction with 2 steps 1: 73.5 percent / sodium hydride / dimethylformamide; toluene / 1 h / 40 - 45 °C 2: 74.5 percent / ethanol / 4 h / 78 - 80 °C View Scheme

3-Amino-2-chloro-4-methylpyridine (133627-45-9) → (Z)-ethyl 3-benzylamino-3-(2-chloro-4-methylpyridin-3-ylamino)-2-cyanoacrylate

Conditions	Yield
Multi-step reaction with 2 steps 1: 73.5 percent / sodium hydride / dimethylformamide; toluene / 1 h / 40 - 45 °C 2: 55.7 percent / ethanol / 4 h / 78 - 80 °C View Scheme

Upstream product

• 23056-39-5 2-chloro-3-nitro-4-methylpyridine 
• 3430-27-1 3-amino-4-methylpyridine 
• 152362-01-1 2-chloro-4-methyl-3-pyridinecarboxamide 
• 5832-44-0 3-nitro-4-methylpyridine 
• 93271-59-1 2-hydroxy-4-methylpyridine-3-carbonitrile 
• 65169-38-2 2-chloro-4-methyl-3-pyridinecarbonitrile 
• 71493-72-6 2-(4-(dimethylamino)but-3-en-2-ylidene)malononitrile 
• 13166-10-4 isopropylidenemalonodinitrile 
• 1679-47-6 3-methyltetrahydro-2-furanone 
• 108-89-4 picoline 
• 21901-18-8 2-hydroxy-4-methyl-3-nitropyridine 
• 6635-86-5 2-amino-4-methyl-3-nitropyridine 
• 152362-00-0 ethyl 2-chloro-2-cyano-3-methyl-5-oxopentanoate 
• 142266-63-5 2-chloro-4-methyl-3-pyridinecarboxylic acid 

Downstream Products

• 133627-46-0 2-chloro-N-(2-chloro-4-methyl-3-pyridinyl)-3-pyridinecarboxamide 
• 133627-47-1 N-(2-chloro-4-methyl-3-pyridinyl)-2-(cyclopropylamino)-3-pyridinecarboxamide 
• 1216164-90-7 4-methyl-N₂-phenylpyridine-2,3-diamine 

Relevant articles and documents

A concise synthesis of 2-chloro-3-amino-4-methylpyridine

An improved and commercially valuable process is developed for the scalable synthesis of 2-chloro-3-amino-4-methylpyridine (CAPIC), a key intermediate of Nevirapine. The synthesis was accomplished in four steps, featuring condensation starting from 4,4-dimethoxyl-2-butanone and cyanoacetamide with ammonium acetate and acetic acid as catalysts. The total yield of the process is 62.1%. The pure CAPIC sample was confirmed with FTIR, 1H NMR, and 13C NMR spectra.

Synthesis, docking study and kinase inhibitory activity of a number of new substituted pyrazolo[3,4-c]pyridines

A series of new pyrazolo[3,4-c]pyridines bearing various 1, 3, 5 or 1, 3, 7 pattern substitutions, were designed and synthesized. Some of them showed interesting inhibitory activity mainly against glycogen synthase kinase 3 (GSK3)α/β as well as against cdc2-like kinases 1 (CLK1) and dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), with good selectivity and remarkable structure-activity relationships (SARs), without being cytotoxic. Molecular simulations in correlation with biological data revealed the importance of the existence of N1-H as well as the absence of a bulky 7-substituent.

DIARYLTHIOHYDANTOIN COMPOUND AS ANDROGEN RECEPTOR ANTAGONIST

The present application belongs to the field of medicine. In particular, the present application relates to a diarylthiohydantoin compound as an androgen receptor antagonist or a pharmaceutically acceptable salt thereof, a preparation method of the same, a pharmaceutical composition comprising the compound, and a use thereof in treating a cell proliferative disease mediated by androgen. The compound of the present application has good antagonistic effect on androgen receptor and exhibits excellent antitumor effect.

Synthesis and Antiproliferative Activity of New pyrazolo[3,4-c]pyridines

Background: Several pyrazolopyridines possess promising pharmacological activities, mainly attributed to their antagonistic nature towards the natural purines in many biological processes. Cytotoxicity and anticancer potential of this class of compounds a