356560-84-4

Basic information

• Product Name: 1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione
• Synonyms: 1,2-Ethanedione, 1-(6-Methyl-2-pyridinyl)-2-[1,2,4]triazolo[1,5-a]pyridin-6-yl-;1-(6-Methyl-2-pyridinyl)-2-[1,2,4]triazolo[1,5-a]pyridine-6-yl-1,2-ethanedione;1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl);1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione
• CAS NO: 356560-84-4
• Molecular Formula: C₁₄H₁₀N₄O₂
• Molecular Weight: 266.26
• EINECS: 1308068-626-2
• Mol File: 356560-84-4.mol
• Article Data: 2

Chemical Properties

• Appearance: /
• Density: 1.39±0.1 g/cm3(Predicted)
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 0.85±0.10(Predicted)
• CAS DataBase Reference: 1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione(CAS DataBase Reference)
• NIST Chemistry Reference: 1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione(356560-84-4)
• EPA Substance Registry System: 1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione(356560-84-4)

Safety Data

• Hazardous Substances Data: 356560-84-4(Hazardous Substances Data)

Usage

Uses

1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione can be used as an intermediate in organic synthesis and pharmaceutical intermediates, mainly used in laboratory research and development processes and chemical production processes.

Synthesis

Preparation of 1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione (a compound of the formula ( V) wherein Ra = CH3) To a stirred suspension of 2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(6-methylpyridin-2-yl)ethanone (6.20 g, 24.57 mmol) in DMSO (48 mL) was added dropwise HBr (48 wt. % in water, 5.96 g, 12.4 mL) at 0°C, and the mixture was heated at 60-70°C. After 2 h, the reaction mixture was cooled to 0°C, poured onto ice water (20 mL), and basified to pH 10 with solid K2CO3. The mixture was extracted with CHCl3 (2 x 250 mL), and the organic phase was washed with water (2 x 100 mL), dried over anhydrous Na2SO4, filtered, and evaporated to dryness under reduced pressure. The residue was purified by MPLC on silica gel using a mixture of MeOH and CH2Cl2 as eluent to give the titled compound. Light yellow solid, yield 6.02 g, 92%

Synthetic route

1-(6-methylpyridin-2-yl)-2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)ethanone (614750-82-2) → 1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione (356560-84-4)

Conditions	Yield
With hydrogen bromide; dimethyl sulfoxide at 60 - 70℃; for 2h;	92%
With water; hydrogen bromide In dimethyl sulfoxide at 60 - 70℃; for 2h;

6-methyl-2-pyridinecarboxaldehyde (1122-72-1) → 1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione (356560-84-4)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: ziconium(IV) oxychloride octahydrate / 1 h / 20 °C 2.1: caesium carbonate / isopropyl alcohol; tetrahydrofuran / 20 °C 2.2: 1 h 2.3: pH 7 - 8 3.1: dimethyl sulfoxide; hydrogen bromide / 2 h / 60 - 70 °C View Scheme

diphenyl (6-methylpyridin-2-yl)(phenylamino)methylphosphonate (614750-85-5) → 1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione (356560-84-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: caesium carbonate / isopropyl alcohol; tetrahydrofuran / 20 °C 1.2: 1 h 1.3: pH 7 - 8 2.1: dimethyl sulfoxide; hydrogen bromide / 2 h / 60 - 70 °C View Scheme

1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione (356560-84-4) + dimethoxyacetaldehyde (51673-84-8) → 6-(2-(dimethoxymethyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)-[1,2,4]triazolo[1,5-a]pyridine (1352609-89-2)

Conditions	Yield
With ammonium acetate In methanol; tert-butyl methyl ether; water at 20℃; for 4h;	83%
With ammonium acetate In methanol; tert-butyl methyl ether; water at 20℃; for 4h;	83%
Stage #1: 1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione; dimethoxyacetaldehyde With ammonium acetate In methanol; tert-butyl methyl ether; water at 20℃; for 3h; Stage #2: With sodium hydrogencarbonate In methanol; tert-butyl methyl ether; water pH=8;	78%

N-phthalimidyl-2-aminoacetaldehyde (2913-97-5) + 1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione (356560-84-4) → 2-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)isoindoline-1,3-dione (1607465-42-8)

Conditions	Yield
With ammonium acetate In methanol; tert-butyl methyl ether at 20 - 50℃; for 10h;	67%

1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione (356560-84-4) + 2-phenoxyethanal (2120-70-9) → 6-(5-(6-methylpyridin-2-yl)-2-(phenoxymethyl)-1H-imidazol-4-yl)-[1,2,4]triazolo[1,5-a]pyridine (1352609-80-3)

Conditions	Yield
With ammonium acetate In methanol; tert-butyl methyl ether at 20℃; for 1.16667h; Inert atmosphere;	56%
With ammonium acetate In methanol; tert-butyl methyl ether at 20℃; Inert atmosphere;	56%

1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione (356560-84-4) + 2-(phenylthio)acetaldehyde (66303-55-7) → 6-(5-(6-methylpyridin-2-yl)-2-((phenylthio)methyl)-1H-imidazol-4-yl)-[1,2,4]triazolo[1,5-a]pyridine (1352609-84-7)

Conditions	Yield
With ammonium acetate In methanol; tert-butyl methyl ether at 20℃; for 1.16667h; Inert atmosphere;	38%
With ammonium acetate In methanol; tert-butyl methyl ether at 20℃; Inert atmosphere;	38%

6,7-dimethoxy-3,4-dihydro-isoquinoline (3382-18-1) + 1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione (356560-84-4) → C25H22N6O2

Conditions	Yield
With ammonium acetate; acetic acid In tert-butyl methyl ether Heating / reflux;	37%

1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione (356560-84-4) + 3-cyanophenyl-1-acetaldehyde (109346-98-7) → 3-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)benzonitrile (1352610-23-1)

Conditions	Yield
Stage #1: 1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione; 3-cyanophenyl-1-acetaldehyde With ammonium acetate In methanol; tert-butyl methyl ether at 20℃; for 1.5h; Inert atmosphere; Stage #2: With sodium hydrogencarbonate In methanol; tert-butyl methyl ether; water pH=8; Inert atmosphere;	33%

1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione (356560-84-4) + 2-((2-fluorophenyl)(methyl)amino)acetaldehyde (1248456-74-7) → N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-fluoro-N-methylaniline (1352609-77-8)

Conditions	Yield
Stage #1: 1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione; 2-((2-fluorophenyl)(methyl)amino)acetaldehyde With ammonium acetate In methanol; tert-butyl methyl ether at 20℃; for 2h; Inert atmosphere; Stage #2: With sodium hydrogencarbonate In methanol; tert-butyl methyl ether; water pH=8; Inert atmosphere;	32%

C8H12ClNO2 (943442-78-2) + 1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione (356560-84-4) → C24H25N7O3 + C24H25N7O3

Conditions	Yield
Stage #1: C8H12ClNO2; 1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione With ethanol; ammonium acetate at 70℃; for 10h; Stage #2: With water; sodium carbonate In ethanol; dichloromethane; water

1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione (356560-84-4) + 1-oxo-2-oxaspiro[4.5]decane-8-carbaldehyde (1097729-60-6) → 8-(5-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)-2-oxaspiro[4.5]decan-1-one (1097729-57-1)

Conditions	Yield
With ammonium acetate; acetic acid In tert-butyl methyl ether Heating / reflux;

1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione (356560-84-4) → N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-3-vinylaniline (1352609-09-6)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: ammonium acetate / water; tert-butyl methyl ether; methanol / 3 h / 20 °C 1.2: pH 8 2.1: hydrogenchloride; water / 3 h / 70 °C 2.2: 0 °C 3.1: acetic acid / 1,2-dichloro-ethane / 2 h / 80 °C 3.2: 0 - 40 °C View Scheme
Multi-step reaction with 4 steps 1: ammonium acetate / methanol; tert-butyl methyl ether; water / 4 h / 20 °C 2: hydrogenchloride / water / 4 h / 70 °C 3: acetic acid / 1,2-dichloro-ethane / 2 h / 120 °C / Inert atmosphere; Sealed tube 4: sodium tetrahydroborate / methanol; tetrahydrofuran / 3 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: ammonium acetate / tert-butyl methyl ether; methanol; water / 4 h / 20 °C 2.1: hydrogenchloride / water / 4 h / 70 °C 3.1: acetic acid / 1,2-dichloro-ethane / 2 h / Reflux; Inert atmosphere 4.1: sodium tetrahydroborate / methanol; tetrahydrofuran / 3 h / 0 - 20 °C 4.2: 0 °C / pH 7-8 View Scheme

1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione (356560-84-4) → 3-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methylamino)-4-((dimethylamino)methyl)benzonitrile (1352609-64-3)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: ammonium acetate / water; tert-butyl methyl ether; methanol / 3 h / 20 °C 1.2: pH 8 2.1: hydrogenchloride; water / 3 h / 70 °C 2.2: 0 °C 3.1: acetic acid / 1,2-dichloro-ethane / 80 °C 3.2: 0 - 20 °C View Scheme
Multi-step reaction with 4 steps 1: ammonium acetate / methanol; tert-butyl methyl ether; water / 4 h / 20 °C 2: hydrogenchloride / water / 4 h / 70 °C 3: acetic acid / 1,2-dichloro-ethane / 2 h / 120 °C / Inert atmosphere; Sealed tube 4: sodium tetrahydroborate / methanol; tetrahydrofuran / 3 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: ammonium acetate / tert-butyl methyl ether; methanol; water / 4 h / 20 °C 2.1: hydrogenchloride / water / 4 h / 70 °C 3.1: acetic acid / 1,2-dichloro-ethane / 2 h / Reflux; Inert atmosphere 4.1: sodium tetrahydroborate / methanol; tetrahydrofuran / 3 h / 0 - 20 °C 4.2: 0 °C / pH 7-8 View Scheme

1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione (356560-84-4) → 4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazole-2-carbaldehyde (1352609-91-6)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: ammonium acetate / water; tert-butyl methyl ether; methanol / 3 h / 20 °C 1.2: pH 8 2.1: hydrogenchloride; water / 3 h / 70 °C 2.2: 0 °C View Scheme
Multi-step reaction with 2 steps 1: ammonium acetate / methanol; tert-butyl methyl ether; water / 4 h / 20 °C 2: hydrogenchloride / water / 4 h / 70 °C View Scheme
Multi-step reaction with 2 steps 1: ammonium acetate / tert-butyl methyl ether; methanol; water / 4 h / 20 °C 2: hydrogenchloride / water / 4 h / 70 °C View Scheme

1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione (356560-84-4) → N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-3-vinylaniline sulfate (1352610-22-0)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: ammonium acetate / water; tert-butyl methyl ether; methanol / 3 h / 20 °C 1.2: pH 8 2.1: hydrogenchloride; water / 3 h / 70 °C 2.2: 0 °C 3.1: acetic acid / 1,2-dichloro-ethane / 2 h / 80 °C 3.2: 0 - 40 °C 4.1: sulfuric acid / ethanol / 0 - 20 °C View Scheme

1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione (356560-84-4) → N-((4-([1,2,4]triazolo[1,5-a]pyridine-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-fluoroaniline (1352608-82-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: ammonium acetate / methanol; tert-butyl methyl ether; water / 4 h / 20 °C 2: hydrogenchloride / water / 4 h / 70 °C 3: acetic acid / 1,2-dichloro-ethane / 2 h / Reflux; Inert atmosphere 4: sodium tetrahydroborate / methanol; tetrahydrofuran / 3 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: ammonium acetate / tert-butyl methyl ether; methanol; water / 4 h / 20 °C 2.1: hydrogenchloride / water / 4 h / 70 °C 3.1: acetic acid / 1,2-dichloro-ethane / 2 h / Reflux; Inert atmosphere 4.1: sodium tetrahydroborate / methanol; tetrahydrofuran / 3 h / 0 - 20 °C 4.2: 0 °C / pH 7-8 View Scheme

1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione (356560-84-4) → N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-chloroaniline (1352608-88-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: ammonium acetate / methanol; tert-butyl methyl ether; water / 4 h / 20 °C 2: hydrogenchloride / water / 4 h / 70 °C 3: acetic acid / 1,2-dichloro-ethane / 2 h / Reflux; Inert atmosphere 4: sodium tris(acetoxy)borohydride / methanol; tetrahydrofuran / 3 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: ammonium acetate / tert-butyl methyl ether; methanol; water / 4 h / 20 °C 2.1: hydrogenchloride / water / 4 h / 70 °C 3.1: acetic acid / 1,2-dichloro-ethane / 2 h / Reflux; Inert atmosphere 4.1: sodium tris(acetoxy)borohydride / methanol; tetrahydrofuran / 3 h / 0 - 20 °C 4.2: 0 °C / pH 7-8 View Scheme

1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione (356560-84-4) → N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-bromoaniline (1352608-94-6)

Conditions	Yield
Multi-step reaction with 4 steps 1: ammonium acetate / methanol; tert-butyl methyl ether; water / 4 h / 20 °C 2: hydrogenchloride / water / 4 h / 70 °C 3: acetic acid / 1,2-dichloro-ethane / 2 h / Reflux; Inert atmosphere 4: sodium tetrahydroborate / methanol; tetrahydrofuran / 3 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: ammonium acetate / tert-butyl methyl ether; methanol; water / 4 h / 20 °C 2.1: hydrogenchloride / water / 4 h / 70 °C 3.1: acetic acid / 1,2-dichloro-ethane / 2 h / Reflux; Inert atmosphere 4.1: sodium tetrahydroborate / methanol; tetrahydrofuran / 3 h / 0 - 20 °C 4.2: 0 °C / pH 7-8 View Scheme

1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione (356560-84-4) → N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-methylaniline (1352608-97-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: ammonium acetate / methanol; tert-butyl methyl ether; water / 4 h / 20 °C 2: hydrogenchloride / water / 4 h / 70 °C 3: acetic acid / 1,2-dichloro-ethane / 2 h / Reflux; Inert atmosphere 4: sodium tris(acetoxy)borohydride / methanol; tetrahydrofuran / 3 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: ammonium acetate / tert-butyl methyl ether; methanol; water / 4 h / 20 °C 2.1: hydrogenchloride / water / 4 h / 70 °C 3.1: acetic acid / 1,2-dichloro-ethane / 2 h / Reflux; Inert atmosphere 4.1: sodium tris(acetoxy)borohydride / methanol; tetrahydrofuran / 3 h / 0 - 20 °C 4.2: 0 °C / pH 7-8 View Scheme

1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione (356560-84-4) → N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-ethylaniline (1352609-03-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: ammonium acetate / methanol; tert-butyl methyl ether; water / 4 h / 20 °C 2: hydrogenchloride / water / 4 h / 70 °C 3: acetic acid / 1,2-dichloro-ethane / 2 h / Reflux; Inert atmosphere 4: sodium tris(acetoxy)borohydride / methanol; tetrahydrofuran / 3 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: ammonium acetate / tert-butyl methyl ether; methanol; water / 4 h / 20 °C 2.1: hydrogenchloride / water / 4 h / 70 °C 3.1: acetic acid / 1,2-dichloro-ethane / 2 h / Reflux; Inert atmosphere 4.1: sodium tris(acetoxy)borohydride / methanol; tetrahydrofuran / 3 h / 0 - 20 °C 4.2: 0 °C / pH 7-8 View Scheme

1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione (356560-84-4) → N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-isopropylaniline (1352609-05-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: ammonium acetate / methanol; tert-butyl methyl ether; water / 4 h / 20 °C 2: hydrogenchloride / water / 4 h / 70 °C 3: acetic acid / 1,2-dichloro-ethane / 2 h / Reflux; Inert atmosphere 4: sodium tris(acetoxy)borohydride / methanol; tetrahydrofuran / 3 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: ammonium acetate / tert-butyl methyl ether; methanol; water / 4 h / 20 °C 2.1: hydrogenchloride / water / 4 h / 70 °C 3.1: acetic acid / 1,2-dichloro-ethane / 2 h / Reflux; Inert atmosphere 4.1: sodium tris(acetoxy)borohydride / methanol; tetrahydrofuran / 3 h / 0 - 20 °C 4.2: 0 °C / pH 7-8 View Scheme

1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione (356560-84-4) → N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-methoxyaniline (1352609-12-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: ammonium acetate / methanol; tert-butyl methyl ether; water / 4 h / 20 °C 2: hydrogenchloride / water / 4 h / 70 °C 3: acetic acid / 1,2-dichloro-ethane / 2 h / Reflux; Inert atmosphere 4: sodium tris(acetoxy)borohydride / methanol; tetrahydrofuran / 3 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: ammonium acetate / tert-butyl methyl ether; methanol; water / 4 h / 20 °C 2.1: hydrogenchloride / water / 4 h / 70 °C 3.1: acetic acid / 1,2-dichloro-ethane / 2 h / Reflux; Inert atmosphere 4.1: sodium tris(acetoxy)borohydride / methanol; tetrahydrofuran / 3 h / 0 - 20 °C 4.2: 0 °C / pH 7-8 View Scheme

1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione (356560-84-4) → N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-(trifluoromethoxy)aniline (1352609-21-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: ammonium acetate / methanol; tert-butyl methyl ether; water / 4 h / 20 °C 2: hydrogenchloride / water / 4 h / 70 °C 3: acetic acid / 1,2-dichloro-ethane / 2 h / Inert atmosphere 4: sodium tetrahydroborate / methanol; tetrahydrofuran / 3 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: ammonium acetate / tert-butyl methyl ether; methanol; water / 4 h / 20 °C 2.1: hydrogenchloride / water / 4 h / 70 °C 3.1: 1,2-dichloro-ethane / 2 h / 20 °C / Inert atmosphere 4.1: sodium tetrahydroborate / methanol; tetrahydrofuran / 3 h / 0 - 20 °C 4.2: 0 °C / pH 7-8 View Scheme

1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione (356560-84-4) → N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-(methylthio)aniline (1352609-24-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: ammonium acetate / methanol; tert-butyl methyl ether; water / 4 h / 20 °C 2: hydrogenchloride / water / 4 h / 70 °C 3: acetic acid / 1,2-dichloro-ethane / 2 h / Reflux; Inert atmosphere 4: sodium tris(acetoxy)borohydride / methanol; tetrahydrofuran / 3 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: ammonium acetate / tert-butyl methyl ether; methanol; water / 4 h / 20 °C 2.1: hydrogenchloride / water / 4 h / 70 °C 3.1: acetic acid / 1,2-dichloro-ethane / 2 h / Reflux; Inert atmosphere 4.1: sodium tris(acetoxy)borohydride / methanol; tetrahydrofuran / 3 h / 0 - 20 °C 4.2: 0 °C / pH 7-8 View Scheme

1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione (356560-84-4) → N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-vinylaniline (1352609-08-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: ammonium acetate / methanol; tert-butyl methyl ether; water / 4 h / 20 °C 2: hydrogenchloride / water / 4 h / 70 °C 3: acetic acid / 1,2-dichloro-ethane / 2 h / Reflux; Inert atmosphere 4: sodium tris(acetoxy)borohydride / methanol; tetrahydrofuran / 3 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: ammonium acetate / tert-butyl methyl ether; methanol; water / 4 h / 20 °C 2.1: hydrogenchloride / water / 4 h / 70 °C 3.1: acetic acid / 1,2-dichloro-ethane / 2 h / Reflux; Inert atmosphere 4.1: sodium tris(acetoxy)borohydride / methanol; tetrahydrofuran / 3 h / 0 - 20 °C 4.2: 0 °C / pH 7-8 View Scheme

1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione (356560-84-4) → 2-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methylamino)benzonitrile (1352609-27-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: ammonium acetate / methanol; tert-butyl methyl ether; water / 4 h / 20 °C 2: hydrogenchloride / water / 4 h / 70 °C 3: acetic acid / 1,2-dichloro-ethane / 2 h / Reflux; Inert atmosphere 4: sodium tetrahydroborate / methanol; tetrahydrofuran / 3 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: ammonium acetate / tert-butyl methyl ether; methanol; water / 4 h / 20 °C 2.1: hydrogenchloride / water / 4 h / 70 °C 3.1: acetic acid / 1,2-dichloro-ethane / 2 h / Reflux; Inert atmosphere 4.1: sodium tetrahydroborate / methanol; tetrahydrofuran / 3 h / 0 - 20 °C 4.2: 0 °C / pH 7-8 View Scheme

1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione (356560-84-4) → 2-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methylamino)benzamide (1352609-31-4)

Conditions	Yield
Multi-step reaction with 5 steps 1: ammonium acetate / methanol; tert-butyl methyl ether; water / 4 h / 20 °C 2: hydrogenchloride / water / 4 h / 70 °C 3: acetic acid / 1,2-dichloro-ethane / 2 h / Reflux; Inert atmosphere 4: sodium tetrahydroborate / methanol; tetrahydrofuran / 3 h / 20 °C / Inert atmosphere 5: sodium hydroxide; dihydrogen peroxide / ethanol / 20 °C View Scheme
Multi-step reaction with 5 steps 1.1: ammonium acetate / tert-butyl methyl ether; methanol; water / 4 h / 20 °C 2.1: hydrogenchloride / water / 4 h / 70 °C 3.1: acetic acid / 1,2-dichloro-ethane / 2 h / Reflux; Inert atmosphere 4.1: sodium tetrahydroborate / methanol; tetrahydrofuran / 3 h / 0 - 20 °C 4.2: 0 °C / pH 7-8 5.1: dihydrogen peroxide; sodium hydroxide / ethanol / 20 °C View Scheme

1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione (356560-84-4) → N-(2-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methylamino)phenyl)methanesulfonamide (1352609-43-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: ammonium acetate / methanol; tert-butyl methyl ether; water / 4 h / 20 °C 2: hydrogenchloride / water / 4 h / 70 °C 3: acetic acid / 1,2-dichloro-ethane / 2 h / Reflux; Inert atmosphere 4: sodium tetrahydroborate / methanol; tetrahydrofuran / 3 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: ammonium acetate / tert-butyl methyl ether; methanol; water / 4 h / 20 °C 2.1: hydrogenchloride / water / 4 h / 70 °C 3.1: acetic acid / 1,2-dichloro-ethane / 2 h / Reflux; Inert atmosphere 4.1: sodium tetrahydroborate / methanol; tetrahydrofuran / 3 h / 0 - 20 °C 4.2: 0 °C / pH 7-8 View Scheme

1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione (356560-84-4) → N-(2-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methylamino)phenyl)acetamide (1352609-40-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: ammonium acetate / methanol; tert-butyl methyl ether; water / 4 h / 20 °C 2: hydrogenchloride / water / 4 h / 70 °C 3: acetic acid / 1,2-dichloro-ethane / 2 h / Reflux; Inert atmosphere 4: sodium tetrahydroborate / methanol; tetrahydrofuran / 3 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: ammonium acetate / tert-butyl methyl ether; methanol; water / 4 h / 20 °C 2.1: hydrogenchloride / water / 4 h / 70 °C 3.1: acetic acid / 1,2-dichloro-ethane / 2 h / Reflux; Inert atmosphere 4.1: sodium tetrahydroborate / methanol; tetrahydrofuran / 3 h / 0 - 20 °C 4.2: 0 °C / pH 7-8 View Scheme

Upstream product

• 1122-72-1 6-methyl-2-pyridinecarboxaldehyde 
• 614750-85-5 diphenyl (6-methylpyridin-2-yl)(phenylamino)methylphosphonate 
• 614750-82-2 1-(6-methylpyridin-2-yl)-2-[1,2,4]triazolo-[1,5-a]pyridin-6-yl-ethanone 

Downstream Products

• 1352609-89-2 6-(2-(dimethoxymethyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)-[1,2,4]triazolo[1,5-a]pyridine 
• 1352609-91-6 4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazole-2-carbaldehyde 
• 1352610-22-0 N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-3-vinylaniline sulfate 
• 1352609-77-8 N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-fluoro-N-methylaniline 
• 1352610-23-1 3-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)benzonitrile 
• 1352609-80-3 6-(5-(6-methylpyridin-2-yl)-2-(phenoxymethyl)-1H-imidazol-4-yl)-[1,2,4]triazolo[1,5-a]pyridine 
• 1352609-84-7 6-(5-(6-methylpyridin-2-yl)-2-((phenylthio)methyl)-1H-imidazol-4-yl)-[1,2,4]triazolo[1,5-a]pyridine 
• 1352608-82-2 N-((4-([1,2,4]triazolo[1,5-a]pyridine-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-fluoroaniline 
• 1352608-88-8 N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-chloroaniline 
• 1352608-94-6 N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-bromoaniline 
• 1352608-97-9 N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-methylaniline 
• 1352609-03-0 N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-ethylaniline 
• 1352609-05-2 N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-isopropylaniline 
• 1352609-12-1 N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-methoxyaniline 

Relevant articles and documents

4-([1,2,4]Triazolo[1,5-a]pyridin-6-yl)-5(3)-(6-methylpyridin-2-yl)imidazole and -pyrazole derivatives as potent and selective inhibitors of transforming growth factor-β type i receptor kinase

A series of 4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5(3)-(6-methylpyridin-2- yl)imidazoles and -pyrazoles 14a-c, 15a-c, 16a, 16b, 19a-d, 21a, and 21b has been synthesized and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. Among them, the pyrazole derivative 21b inhibited ALK5 phosphorylation with an IC50 value of 0.018 μM and showed 95% inhibition at 0.03 μM in a luciferase reporter assay using HaCaT cells permanently transfected with p3TP-luc reporter construct. The 21b showed a high selectivity index of 284 against p38α MAP kinase. The binding pose of 21b generated by docking analysis reveals that it fits well into the ATP binding cavity of ALK5 by forming several hydrogen bond interactions.