183438-97-3

Usage

Uses

Used in Pharmaceutical Industry:
2-Pyridinecarboxaldehyde, 6-ethynyl(9CI) is used as an intermediate in the synthesis of various pharmaceuticals. Its unique structure and functional groups make it a valuable building block for the development of new drugs and therapeutic agents.
Used in Agrochemical Industry:
2-Pyridinecarboxaldehyde, 6-ethynyl(9CI) is also used as an intermediate in the synthesis of agrochemicals. Its chemical properties and reactivity contribute to the development of new pesticides, herbicides, and other agricultural chemicals.
Used in Organic Chemistry:
2-Pyridinecarboxaldehyde, 6-ethynyl(9CI) is used in various chemical reactions as a key intermediate. Its unique structure and functional groups allow for the synthesis of a wide range of organic compounds, making it an important building block in organic chemistry research and development.

Synthetic route

6-(2-trimethylsilylethynyl)pyridin-2-carbaldehyde (183438-94-0) → 6-ethynylpyridine-2-carboxaldehyde (183438-97-3)

Conditions	Yield
With potassium carbonate	98%
With potassium carbonate	98%
With methanol; potassium carbonate at 20℃; for 1h;	83.4%
With potassium carbonate In methanol at 20℃; for 1h; Inert atmosphere;	83.4%

2,6-Dibromopyridine (626-05-1) → 6-ethynylpyridine-2-carboxaldehyde (183438-97-3)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: n-butyllithium / tetrahydrofuran; hexane 1.2: 78 percent / tetrahydrofuran; hexane 2.1: 95 percent / copper(I) iodide / tetrakis(triphenylphosphine)palladium(0) 3.1: 98 percent / potassium carbonate View Scheme
Multi-step reaction with 3 steps 1.1: BuLi / tetrahydrofuran; hexane 1.2: tetrahydrofuran; hexane 1.3: 78 percent / HCl / tetrahydrofuran; hexane 2.1: 95 percent / Pd(PPh3)4; CuI 3.1: 98 percent / K2CO3 View Scheme

6-bromo-2-pyridinecarbaldehyde (34160-40-2) → 6-ethynylpyridine-2-carboxaldehyde (183438-97-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 95 percent / copper(I) iodide / tetrakis(triphenylphosphine)palladium(0) 2: 98 percent / potassium carbonate View Scheme
Multi-step reaction with 2 steps 1: 95 percent / Pd(PPh3)4; CuI 2: 98 percent / K2CO3 View Scheme
Multi-step reaction with 2 steps 1: bis-triphenylphosphine-palladium(II) chloride; triethylamine; copper(l) iodide / 20 °C / Inert atmosphere 2: potassium carbonate; methanol / 1 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: copper(l) iodide; trans-bis(triphenylphosphine)palladium dichloride; triethylamine / 20 °C / Inert atmosphere 2: potassium carbonate / methanol / 1 h / 20 °C / Inert atmosphere View Scheme

2-bromo-6-(4-hexyl-phenylethynyl)-pyridine (762262-22-6) + 6-ethynylpyridine-2-carboxaldehyde (183438-97-3) → 2-formyl-6-[6-(4-hexylphenylethynyl)pyridin-2-ylethynyl]pyridine (804555-76-8)

Conditions	Yield
With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0) Sonogashira coupling;	74%
With copper(l) iodide; diisopropylamine; tetrakis(triphenylphosphine) palladium(0) In toluene at 40℃; for 12h; Sonogashira coupling;	74%

pentafluoro(4-iodophenyl)-λ6-sulfane (286947-68-0) + 6-ethynylpyridine-2-carboxaldehyde (183438-97-3) → 6-((4-(pentafluorothio)phenyl)ethynyl)picolinaldehyde (1401165-57-8)

Conditions	Yield
With triethylamine; bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide In acetonitrile at 20 - 80℃; for 0.5h;	57%

4-(6-(3,6-diazabicyclo[3.1.1]heptan-3-yl)pyridin-3-yl)-6-(1-methyl-1H-pyrazol-4-yl)pyrazole[1,5-a]pyridine-3-carbonitrile dihydrochloride + 6-ethynylpyridine-2-carboxaldehyde (183438-97-3) → 4-(6-(6-((6-ethynylpyridin-2-yl)methyl)-3,6-diazabicyclo[3.1.1]hept-3-yl)pyridin-3-yl)-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile

Conditions	Yield
With sodium tris(acetoxy)borohydride In 1,2-dichloro-ethane at 35℃;	48.93%

6-ethynylpyridine-2-carboxaldehyde (183438-97-3) → C92H66N4

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 74 percent / Pd(PPh3)4; CuI 2.1: BuLi / tetrahydrofuran; hexane / 2 h / -78 °C 2.2: ClP(O)(OEt)2 / tetrahydrofuran; hexane / 2 h / 20 °C 2.3: 53 percent / lithium hexamethyldisilazide / tetrahydrofuran; hexane / 2 h / -78 - 20 °C View Scheme

pentafluoro(4-iodophenyl)-λ6-sulfane (286947-68-0) + 6-ethynylpyridine-2-carboxaldehyde (183438-97-3) → (2R)-3-methyl-2-{[(6-{[4-(pentafluoro-λ6-sulfanyl)phenyl]ethynyl}pyridin-2-yl)methyl]amino}butan-1-ol

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylamine / copper(l) iodide; bis-triphenylphosphine-palladium(II) chloride / acetonitrile / 0.5 h / 20 - 80 °C 2: acetic acid / MP-cyanoborohydride / dichloromethane; methanol / 20 °C View Scheme

formaldehyd (50-00-0) + N,N-diethyl-1,4-phenylenediamine dihydrochloride (2198-58-5, 16713-15-8, 84609-46-1) + 6-ethynylpyridine-2-carboxaldehyde (183438-97-3) → 2-(4-(diethylamino)phenyl)-5-ethynyl-2H-imidazo[1,5-a]pyridin-4-ium chloride

Conditions	Yield
In ethanol at 20 - 25℃;

4-(6-(3,6-diazabicyclo[3.1.1]heptan-3-yl)pyridin-3-yl)-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-carbonitrile dihydrochloride + 6-ethynylpyridine-2-carboxaldehyde (183438-97-3) → 4-(6-(6-((6-ethynylpyridin-2-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)pyridin-3-yl)-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-carbonitrile

Conditions	Yield
With sodium tris(acetoxy)borohydride In 1,2-dichloro-ethane at 35℃; Inert atmosphere;

Upstream product

• 34160-40-2 6-bromo-2-pyridinecarbaldehyde 
• 626-05-1 2,6-Dibromopyridine 
• 183438-94-0 6-(2-trimethylsilylethynyl)pyridin-2-carbaldehyde 

Downstream Products

• 804555-76-8 2-formyl-6-[6-(4-hexylphenylethynyl)pyridin-2-ylethynyl]pyridine 
• 1401165-57-8 6-((4-(pentafluorothio)phenyl)ethynyl)picolinaldehyde 

Relevant academic research and scientific papers

RET INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF

Provided herein are a RET inhibitor, a pharmaceutical composition thereof and uses thereof. In particular, provided is a compound having Formula (I) or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof. Provided is a pharmaceutical composition comprising the compound, and uses of the compound and pharmaceutical composition thereof for the preparation of a medicament, in particular for treatment and prevention of RET-related diseases and conditions, including cancer, irritable bowel syndrome, and/or pain associated with irritable bowel syndrome.

RET INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF

Provided herein are a RET inhibitor, a pharmaceutical composition thereof and uses thereof. In particular, provided is a compound having Formula (I) or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof. Provided is a pharmaceutical composition comprising the compound, and uses of the compound and pharmaceutical composition thereof for the preparation of a medicament, in particular for treatment and prevention of RET-related diseases and conditions, including cancer, irritable bowel syndrome, and/or pain associated with irritable bowel syndrome.

Double elimination protocol for the synthesis of arylene ethynylenes containing heteroaromatic rings

The double elimination reaction of β-substituted sulfones offers a versatile strategy for synthesis of arylene ethynylene kits containing heteroaromatic rings. A sequence of aldol reaction between α-sulfonyl carbanion and aldehyde, trapping the resulting aldolate to give β-substituted sulfone, and double elimination of this intermediate can be integrated in one pot. This protocol allows thiophene, pyridine, and ferrocene units to be accommodated in phenylene ethynylene arrays.

Double elimination protocol for access to pyridine-containing arylene-ethynylenes

The arylene-ethynylene arrays involving pyridine were constructed successfully by taking advantage of double elimination reaction of β-substituted sulfones (sulfoximines) which are easily accessible from arylmethyl sulfones (sulfoximines) and aromatic aldehydes. This protocol was utilized for synthesis of an enantiopure arylene-ethynylene framework bearing a binaphthyl stereogenic core.