171290-52-1

Basic information

• Product Name: 1-ETHYNYL-3 5-DIMETHOXYBENZENE 98
• Synonyms: 1-ETHYNYL-3 5-DIMETHOXYBENZENE 98;1-Ethylnyl-3,5-dimethoxybenzene;Benzene, 1-ethynyl-3,5-diMethoxy-;1-Ethynyl-3,5-diMethoxybenzene 98% (CP)
• CAS NO: 171290-52-1
• Molecular Formula: C₁₀H₁₀O₂
• Molecular Weight: 162.1852
• Product Categories: Alkynes;Organic Building Blocks;Terminal
• Mol File: 171290-52-1.mol
• Article Data: 20

Chemical Properties

• Melting Point: 44-48 °C(lit.)
• Boiling Point: 264.1±30.0℃ (760 Torr)
• Flash Point: >230 °F
• Appearance: /
• Density: 1.06±0.1 g/cm3 (20 ºC 760 Torr)
• Vapor Pressure: 0.0162mmHg at 25°C
• Refractive Index: 1.522
• Storage Temp.: Keep in dark place,Sealed in dry,Room Temperature
• CAS DataBase Reference: 1-ETHYNYL-3 5-DIMETHOXYBENZENE 98(CAS DataBase Reference)
• NIST Chemistry Reference: 1-ETHYNYL-3 5-DIMETHOXYBENZENE 98(171290-52-1)
• EPA Substance Registry System: 1-ETHYNYL-3 5-DIMETHOXYBENZENE 98(171290-52-1)

Safety Data

• Hazard Codes: Xn
• Statements: 36-42/43
• Safety Statements: 22-26-36/37-45
• WGK Germany: 3
• Hazardous Substances Data: 171290-52-1(Hazardous Substances Data)

Usage

General Description

1-ETHYNYL-3,5-DIMETHOXYBENZENE 98 is a chemical compound with the molecular formula C10H10O2. It is a white to light yellow crystalline powder that is primarily used in the pharmaceutical and agrochemical industries. 1-ETHYNYL-3 5-DIMETHOXYBENZENE 98 is known for its potential use as a building block in organic synthesis and is often employed in the production of various pharmaceuticals. It is also used as an intermediate in the synthesis of other organic compounds, and it is important to handle with care as it may cause skin and eye irritation. Additionally, it is important to store this compound in a cool, dry place away from sources of heat and ignition as it is highly flammable.

InChI:InChI=1/C10H10O2/c1-4-8-5-9(11-2)7-10(6-8)12-3/h1,5-7H,2-3H3

Synthetic route

1-(3,5-dimethoxyphenyl)-2-(trimethylsilyl)acetylene (400608-30-2) → 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1)

Conditions	Yield
With tetrabutyl ammonium fluoride In tetrahydrofuran for 0.0833333h;	100%
With potassium carbonate In methanol at 20℃; for 2h;	96%
With potassium carbonate In methanol at 20℃; for 2h;	96%

1-(2,2-dibromoethen-1-yl)-3,5-dimethoxybenzene (205746-51-6) → 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1)

Conditions	Yield
With n-butyllithium for 10h;	94%
With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 1.5h;	86%
With n-butyllithium In tetrahydrofuran; hexane at -50℃; Schlenk technique; Inert atmosphere;	81%

2-methyl-4-(3,5-dimethoxyphenyl)-3-butyn-2-ol (171290-51-0) → 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1)

Conditions	Yield
With potassium hydroxide In toluene at 65℃; for 24h;	85%
With potassium hydroxide at 100 - 135℃; Yield given;
With potassium hydroxide In toluene for 24h; Reflux; Inert atmosphere;

3,5-dimethoxybenzaldehdye (7311-34-4) + dimethyl 1-(1-diazo-2-oxopropyl)phosphonate (90965-06-3) → 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1)

Conditions	Yield
With potassium carbonate In methanol at 20℃; for 12h; Inert atmosphere;	57%

1-(3,5-dimethoxyphenyl)ethan-1-one (39151-19-4) → 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1)

Conditions	Yield
With diethyl chlorophosphate; lithium diisopropyl amide Yield given. Multistep reaction;

1-iodo-3,5-dimethoxybenzene (25245-27-6) → 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / Pd(PPh3)2Cl2; CuI; PPh3 / triethylamine / 48 h / 50 °C 2: 100 percent / TBAF / tetrahydrofuran / 0.08 h View Scheme
Multi-step reaction with 2 steps 1: Et3N, pyridine, Ph3P, CuI / (Ph3P)2PdCl2 / 14 h / 25 °C 2: KOH / 100 - 135 °C View Scheme
Multi-step reaction with 2 steps 1: copper(l) iodide / bis-triphenylphosphine-palladium(II) chloride / 20 °C / Inert atmosphere 2: potassium fluoride; methanol / 2 h / 20 °C View Scheme

3,5-Dimethoxyaniline (10272-07-8) → 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: aq. HCl; NaNO2 / 0 °C 1.2: 50 percent / aq. KI / 20 °C 2.1: 85 percent / Pd(PPh3)2Cl2; CuI; PPh3 / triethylamine / 48 h / 50 °C 3.1: 100 percent / TBAF / tetrahydrofuran / 0.08 h View Scheme
Multi-step reaction with 4 steps 1: hydrogenchloride; sodium nitrite / water / -10 - 5 °C / Cooling with acetone-dry ice 2: potassium iodide / water / 20 °C 3: copper(l) iodide / bis-triphenylphosphine-palladium(II) chloride / 20 °C / Inert atmosphere 4: potassium fluoride; methanol / 2 h / 20 °C View Scheme

3,5-dimethoxybenzoic acid (1132-21-4) → 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 2.) trimethylchlorosilane, 3.) 0.5 N HCl 2: 1.) LDA, 2.) diethyl chlorophosphate, 3.) LDA View Scheme

carbon tetrabromide (558-13-4) + 3,5-dimethoxybenzaldehdye (7311-34-4) → 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1)

Conditions	Yield
Stage #1: carbon tetrabromide; 3,5-dimethoxybenzaldehdye With triphenylphosphine In dichloromethane at 0 - 20℃; for 0.5h; Ramirez-Corey-Fuchs reaction; Stage #2: With lithium diisopropyl amide In tetrahydrofuran; n-heptane; ethylbenzene at -78℃; for 2h; Ramirez-Corey-Fuchs reaction; Stage #3: With ammonium chloride In tetrahydrofuran; n-heptane; ethylbenzene Ramirez-Corey-Fuchs reaction;	72 mg

3,5-dimethoxybenzaldehdye (7311-34-4) → 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: triphenylphosphine / dichloromethane / 0.5 h / 0 - 20 °C 2: lithium diisopropyl amide / tetrahydrofuran; n-heptane; ethylbenzene / 2 h / -78 °C View Scheme
Multi-step reaction with 2 steps 1.1: triphenylphosphine / dichloromethane / 0.5 h / 0 °C / Inert atmosphere; Schlenk technique 1.2: Inert atmosphere; Schlenk technique 2.1: n-butyllithium / tetrahydrofuran; hexane / -50 °C / Schlenk technique; Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: triphenylphosphine / dichloromethane / 1.25 h / 0 °C / Inert atmosphere; Schlenk technique 2: caesium carbonate / dimethyl sulfoxide / 115 °C / Sealed tube; Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: triphenylphosphine / dichloromethane / 2 h / 0 °C / Inert atmosphere 2: 1,8-diazabicyclo[5.4.0]undec-7-ene / acetonitrile / 16 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1.1: triphenylphosphine / dichloromethane / 0.5 h / 0 - 5 °C 1.2: 16 h / 20 °C 2.1: n-butyllithium / hexane; tetrahydrofuran / 16.5 h / Inert atmosphere View Scheme

1-bromo-3,5-dimethoxybenzene (20469-65-2) → 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: tris-(dibenzylideneacetone)dipalladium(0); (dimethylamino)trimethyltin; triphenylphosphine / toluene / 8 h / Inert atmosphere; Reflux 2: tetrabutyl ammonium fluoride / dichloromethane / 5 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: triphenylphosphine; copper(l) iodide; bis-triphenylphosphine-palladium(II) chloride; triethylamine / 24 h / Reflux; Inert atmosphere 2: potassium hydroxide / toluene / 24 h / 65 °C View Scheme
Multi-step reaction with 2 steps 1: triethylamine; bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide / N,N-dimethyl-formamide / 12 h / 80 °C / Inert atmosphere 2: potassium carbonate / methanol / 2 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: triethylamine; bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide / N,N-dimethyl-formamide / 12 h / 80 °C / Inert atmosphere 2: potassium carbonate / methanol / 2 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine / 24 h / Reflux; Inert atmosphere 2: potassium hydroxide / toluene / 24 h / Reflux; Inert atmosphere View Scheme

3,5-Dimethoxy-benzenediazonium; chloride (86988-56-9) → 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium iodide / water / 20 °C 2: copper(l) iodide / bis-triphenylphosphine-palladium(II) chloride / 20 °C / Inert atmosphere 3: potassium fluoride; methanol / 2 h / 20 °C View Scheme

3,5-dimethoxyphenethyl alcohol (7417-20-1) → 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium carbonate; fluorosulfonyl fluoride; dimethyl sulfoxide / 2 h / 20 °C 2: cesium fluoride / dimethyl sulfoxide / 2 h / 100 °C View Scheme

C10H11FO5S → 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1)

Conditions	Yield
With cesium fluoride In dimethyl sulfoxide at 100℃; for 2h;	224 mg

4-bromo-benzaldehyde (1122-91-4) + trimethylsilylacetylene (1066-54-2) → 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1)

Conditions	Yield
Sonogashira Cross-Coupling;

1-(benzenesulfonyl)-5-bromo-1H-pyrrolo[2,3-b]pyridine (1001070-33-2) + 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1) → 1-(benzenesulfonyl)-5-[2-(3,5-dimethoxyphenyl)ethynyl]-1H-pyrrolo[2,3-b]pyridine

Conditions	Yield
With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); N-ethyl-N,N-diisopropylamine In acetonitrile at 80℃; for 1.5h; Inert atmosphere; Sealed tube;	100%

(Z)-N-benzylidenebenzylamine N-oxide (77681-22-2, 3376-26-9, 85225-56-5) + 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1) → N-benzyl-N-(3-(3,5-dimethoxyphenyl)-1-phenylprop-2-yn-1-yl)-hydroxylamine

Conditions	Yield
Stage #1: (Z)-N-benzylidenebenzylamine N-oxide; 1-Ethynyl-3,5-dimethoxy-benzene With trimethylsilyl trifluoromethanesulfonate; N-ethyl-N,N-diisopropylamine; zinc dibromide In diethyl ether at 20℃; for 2h; Inert atmosphere; Stage #2: With toluene-4-sulfonic acid In methanol for 2h;	100%

para-iodoanisole (696-62-8) + 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1) → 1,3-dimethoxy-5-((4-methoxyphenyl)ethynyl)benzene (400608-31-3)

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 20℃; for 18h; Sonogashira coupling; Inert atmosphere;	99%
With copper(l) iodide; bis-triphenylphosphine-palladium(II) chloride at 20℃; for 6h; Inert atmosphere;	93%
With pyrrolidine; palladium diacetate; triphenylphosphine for 1h; Sonogashira Cross-Coupling; Inert atmosphere; Reflux;	93%
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 0 - 20℃; for 18h; Inert atmosphere; Schlenk technique;	80%
With pyrrolidine; triphenylphosphine; palladium 10% on activated carbon at 85℃; for 17h; Sonogashira Coupling; Inert atmosphere;	75%

1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1) + (2R,3S)-5β-azido-2-{[(4-methylbenzoyl)oxy]methyl}tetrahydrofuran-3-yl 4-methylbenzoate (234106-08-2) → 1-[2′-deoxy-3′,5′-bis{O-(p-toluoyl)}-β-D-ribofuranosyl]-4-(3,5-dimethoxyphenyl)-1H-1,2,3-triazole (1416717-98-0)

Conditions	Yield
With copper(II) sulfate; sodium L-ascorbate; N-ethyl-N,N-diisopropylamine In tetrahydrofuran; water at 75 - 80℃; Inert atmosphere;	99%

N-(tert-butoxycarbonyl)-1,4-dihydro-1,4-iminonaphthalene (5176-28-3) + 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1) → C25H27NO4

Conditions

Yield

Stage #1: N-(tert-butoxycarbonyl)-1,4-dihydro-1,4-iminonaphthalene With (R)-1-[(Sp)-2-(dicyclohexylphosphanyl)ferrocenylethyl]diphenylphosphane; rhodium(III) chloride trihydrate In 1,2-dimethoxyethane at 20℃; for 0.333333h; Inert atmosphere; Schlenk technique; Stage #2: 1-Ethynyl-3,5-dimethoxy-benzene In 1,2-dimethoxyethane at 70℃; for 30h; Inert atmosphere; Schlenk technique; enantioselective reaction;

98%

N-(tert-butoxycarbonyl)-1,4-dihydro-1,4-iminonaphthalene (5176-28-3) + 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1) → tert-butyl ((1R,2S)-2-((3,5-dimethoxyphenyl)ethynyl)-1,2-dihydronaphthalen-1-yl)carbamate (1575707-08-2)

Conditions

Yield

Stage #1: N-(tert-butoxycarbonyl)-1,4-dihydro-1,4-iminonaphthalene With (R)-(+)-2,2'-bis[bis(3,5-dimethylphenyl)phosphino]-1,1'-binaphthyl; copper(I) trifluoromethanesolfonate toluene complex; palladium diacetate In 1,2-dimethoxyethane at 0 - 20℃; for 0.5h; Inert atmosphere; Schlenk technique; Stage #2: 1-Ethynyl-3,5-dimethoxy-benzene In 1,2-dimethoxyethane for 6h; Inert atmosphere; Schlenk technique;

98%

3-azido-N-(3-(trifluoromethyl)phenyl)benzamide + 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1) → 3-(4-(3,5-dimethoxyphenyl)-1H-1,2,3-triazol-1-yl)-N-(3-(trifluoromethyl)phenyl)benzamide

Conditions	Yield
With copper(II) sulfate; sodium L-ascorbate In water; tert-butyl alcohol at 20℃; for 2h; Inert atmosphere;	98%
With copper(II) sulfate; sodium L-ascorbate In water; tert-butyl alcohol at 20℃; for 2h;	98%

methyl 3-formyl-2-(2-iodophenyl)indolizine-1-carboxylate + 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1) → methyl 2-(2-((3,5-dimethoxyphenyl)ethynyl)phenyl)-3-formylindolizine-1-carboxylate

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In acetonitrile at 100℃; for 2h; Sonogashira Cross-Coupling;	98%

C154H267N11O42 (942620-37-3) + 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1) → C162H273O42N11O2CH2CH2

Conditions	Yield
With copper(II) sulfate; sodium L-ascorbate In water; tert-butyl alcohol for 0.166667h; microwave irradiation;	97%

2-methoxy-1,4-benzoquinone (2880-58-2) + 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1) → 4-((3,5-dimethoxyphenyl)ethynyl)-4-hydroxy-3-methoxycyclohexa-2,5-dien-1-one (1193360-00-7)

Conditions	Yield
Stage #1: 1-Ethynyl-3,5-dimethoxy-benzene With n-butyllithium In tetrahydrofuran at -78℃; for 0.0833333h; Inert atmosphere; Stage #2: 2-methoxy-1,4-benzoquinone In tetrahydrofuran at -78℃; for 0.25h; Inert atmosphere;	96%
Stage #1: 1-Ethynyl-3,5-dimethoxy-benzene With n-butyllithium In tetrahydrofuran; hexane at -78℃; Stage #2: 2-methoxy-1,4-benzoquinone In tetrahydrofuran; hexane at -78℃; Stage #3: With water; ammonium chloride In tetrahydrofuran; hexane

ortho-bromobenzaldehyde (6630-33-7) + 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1) → 2-((3,5-dimethoxyphenyl)ethynyl)benzaldehyde (1078710-66-3)

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 50℃; for 6h; Sonogashira coupling;	96%
With copper(l) iodide; palladium diacetate; triethylamine; triphenylphosphine In tetrahydrofuran at 80℃; for 12h;
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 60℃; for 4h; Inert atmosphere;

1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1) + 2,2-dipivaloylamino-4-methyl-5-iodo-7-(N-benzyl)pyrrolo[2,3-d]pyrimidine (306315-01-5) → N-{7-benzyl-4-methyl-5-[(3,5-dimethoxyphenyl)ethynyl]-7H-pyrrolo[2,3-d]pyrimidin-2-yl}-N-(2,2-dimethylpropanoyl)-2,2-dimethylpropanamide (1321913-92-1)

Conditions	Yield
With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine In 1,1-dichloroethane at 20℃; for 24h; Sonogashira coupling; Inert atmosphere; Darkness;	96%

5-(azidomethyl)-3-(3,4-dimethoxyphenyl)isoxazole + 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1) → 3-(3,4-dimethoxyphenyl)-5-((4-(3,5-dimethoxyphenyl)-1H-1,2,3-triazol-1-yl)methyl)isoxazole

Conditions	Yield
With copper(II) sulfate; sodium L-ascorbate In water; N,N-dimethyl-formamide at 70℃; for 0.166667h; Sealed tube; Microwave irradiation;	96%

8-bromo-2'-deoxyadenosine (14985-44-5) + 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1) → 2-(6-amino-8-((3,5-dimethoxyphenyl)ethynyl)-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol (1350627-76-7)

Conditions	Yield
With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine In N,N-dimethyl-formamide at 20℃; for 18h; Sonogashira coupling; Inert atmosphere;	95%

1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1) + (2R,3S)-5α-azido-2-{[(4-methylbenzoyl)oxy]methyl}tetrahydrofuran-3-yl 4-methylbenzoate (316354-49-1) → C31H31N3O7

Conditions	Yield
With copper(II) sulfate; sodium L-ascorbate; diisopropylamine In tetrahydrofuran; water at 75 - 80℃; for 12h; Inert atmosphere;	95%

Dimethylphenylsilane (766-77-8) + 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1) → ((3,5-dimethoxyphenyl)ethynyl)dimethyl(phenyl)silane

Conditions	Yield
With sodium hydroxide In 1,2-dimethoxyethane at 65℃; for 48h;	95%

benzyl azide (622-79-7) + 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1) → 1-benzyl-4-(3,5-dimethoxyphenyl)-1H-1,2,3-triazole

Conditions	Yield
With copper(ll) sulfate pentahydrate; betaine; sodium L-ascorbate In water at 30℃; for 24h;	95%

methyl 5-azido-2-hydroxybenzoate (1239028-02-4) + 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1) → methyl 2-hydroxy-5-[4-(3,5-dimethoxyphenyl)-1H-1,2,3-triazol-1-yl]benzoate (1239028-26-2)

Conditions	Yield
With copper(II) sulfate; sodium L-ascorbate In water; dimethyl sulfoxide; tert-butyl alcohol at 20℃; for 96h; Inert atmosphere;	94%

1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1) → (E)-2,2'-(but-1-en-3-yne-1,4-diyl)bis(2,6-dimethoxybenzene) (1261302-47-9)

Conditions	Yield
With C77H74N2OPtSi2 In toluene at 60℃; Reagent/catalyst; Inert atmosphere; diastereoselective reaction;	94%
With [{Pd(μ-OH)Cl(1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene)}2]; potassium hydroxide In ethanol at 22℃; for 24h; Reagent/catalyst; Solvent; Temperature; Inert atmosphere; Schlenk technique; stereoselective reaction;	94%
With CoH(P(CH3)3)4 In tetrahydrofuran at 20℃; for 2h; Schlenk technique; Inert atmosphere; stereoselective reaction;	63%
With [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; acetic acid In tetrahydrofuran; methanol; water at 20℃; for 7h; Inert atmosphere; optical yield given as %de; stereoselective reaction;	0.116 g

3-chloro-6-methoxypyridazine (1722-10-7) + 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1) → 3-[(3,5-dimethoxyphenyl)ethynyl]-6-methoxypyridazine

Conditions	Yield
With dichloro bis(acetonitrile) palladium(II); dicyclohexyl(2',4',6'-triisopropyl-[1,1':3',1''-terphenyl]-2-yl)phosphane; triethylamine In tetrahydrofuran at 60℃; for 6h; Sonogashira Cross-Coupling; Sealed tube;	94%

methanol (67-56-1) + carbon monoxide (201230-82-2) + 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1) → dimethyl 2-(3,5-dimethoxyphenyl)succinate

Conditions	Yield
With 1,3-bis(tert-butyl(pyridin-2-yl)phosphanyl)propane; palladium(II) acetylacetonate; toluene-4-sulfonic acid at 100℃; under 30003 Torr; for 20h; Sealed tube; chemoselective reaction;	94%

2-iodobenzyl alcohol (5159-41-1) + 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1) → [2-(3,5-dimethoxyphenylethynyl)phenyl]methanol (1205555-43-6)

Conditions

Yield

Stage #1: 2-iodobenzyl alcohol With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide In N,N-dimethyl-formamide at 20℃; for 0.0833333h; Sonogashira coupling; Inert atmosphere; Stage #2: With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20 - 70℃; Sonogashira coupling; Inert atmosphere; Stage #3: 1-Ethynyl-3,5-dimethoxy-benzene In N,N-dimethyl-formamide at 70℃; for 2.16667h; Sonogashira coupling; Inert atmosphere;

93%

2-bromo-3-thiophenecarboxylic acid-2-pyridyl ester (1382312-69-7) + 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1) → C15H11BrO3S (1382312-86-8)

Conditions	Yield
Stage #1: 1-Ethynyl-3,5-dimethoxy-benzene With ethylmagnesium bromide In tetrahydrofuran at 0 - 20℃; for 0.5h; Inert atmosphere; Stage #2: 2-bromo-3-thiophenecarboxylic acid-2-pyridyl ester In tetrahydrofuran at 0℃; for 0.5h;	93%

N-(4-azidobenzoyl)-L-homoserine lactone (1421345-74-5) + 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1) → C21H20N4O5 (1421345-53-0)

Conditions	Yield
With copper(l) iodide; N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 16h; Inert atmosphere;	93%

5-bromo-N-{3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}pyrimidin-2-amine (1453211-46-5) + 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1) → 5-[(3,5-dimethoxyphenyl)ethynyl]-N-{3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}pyrimidin-2-amine (1453207-54-9)

Conditions	Yield
With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine In N,N-dimethyl-formamide at 110℃; for 4h; Sonogashira Cross-Coupling;	93%
With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine In N,N-dimethyl-formamide at 120℃; for 2.5h; Inert atmosphere;	23 mg

1,4-dihydro-9-isopropylidene-6,7-dimethoxy-1,4-methanonaphthalene + 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1) → (1R*,4S*)-2-((3,5-dimethoxyphenyl)ethynyl)-6,7-dimethoxy-9-(propan-2-ylidene)-1,2,3,4-tetrahydro-1,4-methanonaphthalene

Conditions	Yield
With bis(1,5-cyclooctadiene)diiridium(I) dichloride; (+)-(R)-[2,3,2',3'-tetrahydro-5,5'-bi(1,4-benzodioxin)-6,6'-diyl]bis(diphenylphosphane) In 1,2-dichloro-ethane at 70℃; for 5h; Inert atmosphere; Schlenk technique; enantioselective reaction;	93%

(1-azido-2,5-di-O-acetyl-3-O-benzoyl-6-deoxy-6-diethylphosphono)-β-ribo-(5S)-hexafuranose + 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1) → 3-O-benzoyl-6-deoxy-2,5-O-diacetyl-6-diethylphosphono-1-(4-(3,5-dimethoxyphenyl)-1H-1,2,3-triazol-1-yl)-β-D-allofuranose

Conditions	Yield
With copper(l) iodide; N-ethyl-N,N-diisopropylamine In tetrahydrofuran Huisgen Cycloaddition; Reflux; regioselective reaction;	93%

1-bromo-N,N'-bis(2,4-dimethylpent-3-yl)perylene-3,4:9,10-tetracarboxylic diimide (946489-25-4) + 1-Ethynyl-3,5-dimethoxy-benzene (171290-52-1) → C48H46N2O6 (1621187-01-6)

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; diisopropylamine In tetrahydrofuran at 70 - 80℃; Schlenk technique; Inert atmosphere;	92%

Upstream product

• 171290-51-0 2-methyl-4-(3,5-dimethoxyphenyl)-3-butyn-2-ol 
• 39151-19-4 1-(3,5-dimethoxyphenyl)ethan-1-one 
• 400608-30-2 1-(3,5-dimethoxyphenyl)-2-(trimethylsilyl)acetylene 
• 205746-51-6 3,5-dimethoxy-β,β-dibromostyrene 
• 1122-91-4 4-bromo-benzaldehyde 
• 1066-54-2 trimethylsilylacetylene 
• 7311-34-4 3,5-dimethoxybenzaldehdye 
• 90965-06-3 dimethyl 1-(1-diazo-2-oxopropyl)phosphonate 
• 7417-20-1 3,5-dimethoxyphenethyl alcohol 
• 86988-56-9 3,5-Dimethoxy-benzenediazonium; chloride 
• 20469-65-2 1-bromo-3,5-dimethoxybenzene 
• 558-13-4 carbon tetrabromide 
• 1132-21-4 3,5-dimethoxybenzoic acid 
• 10272-07-8 3.5-dimethoxyaniline 

Downstream Products

• 180989-35-9 1-(3,5-dimethoxyphenyl)-1-heptyne 
• 220169-81-3 (S)-1-benzyloxy-5-(3,5-dimethoxyphenyl)-2-methylpent-4-yne 
• 220170-09-2 (R)-1-benzyloxy-5-(3,5-dimethoxyphenyl)-2-methylpent-4-yne 
• 249504-85-6 2-(3,5-dimethoxyphenyl)-1H-indene 
• 1017277-96-1 cis-1,6-bis(3,5-dimethoxyphenyl)-hex-1,5-diyne-3-ene 
• 1050503-23-5 C₂₃H₁₆O₃ 
• 1051385-16-0 5,7-dimethoxy-4-phenylnaphtho[2,3-c]furan-1(3H)-one 
• 1051385-27-3 C₂₀H₁₆O₄ 
• 1193360-00-7 4-((3,5-dimethoxyphenyl)ethynyl)-4-hydroxy-3-methoxycyclohexa-2,5-dien-1-one 
• 1193359-75-9 C₁₆H₁₄O₄ 
• 1205555-43-6 [2-(3,5-dimethoxyphenylethynyl)phenyl]methanol 
• 1228178-68-4 2-(3,5-dimethoxyphenyl)-5-nitrobenzo[b]furan 
• 1229971-81-6 (E)-(3,5-dimethoxystyryl)dimethyl(perfluorophenyl)silane 
• 1229971-84-9 (1-(3,5-dimethoxyphenyl)vinyl)dimethyl(perfluorophenyl)silane 

Relevant articles and documents

1,2-Carbopentafluorophenylation of Alkynes: The Metallomimetic Pull-Push Reactivity of Tris(pentafluorophenyl)borane

We report the novel single-step 1,2-dicarbofunctionalization of an arylacetylene with an allylsilane and tris(pentafluorophenyl)borane [B(C6F5)3] involving C?C bond formation with C?H bond scission at the β-position to the silicon atom of an allylsilane and B→C migration of a C6F5 group. The 1,2-carbopentafluorophenylation occurs smoothly without the requirement for a catalyst or heating. Mechanistic studies suggest that the metallomimetic “pull-push” reactivity of B(C6F5)3 imparts consecutive electrophilic and nucleophilic characteristics to the benzylic carbon of the arylacetylene. Subsequent photochemical 6π-electrocyclization affords tetrafluoronaphthalenes, which are important in the pharmaceutical and materials sciences. Owing to the unique reactivity of B(C6F5)3, the 1,2-carbopentafluorophenylation using 2-substituted furan proceeded with ring opening, and the reaction using silyl enolates formed a C?C bond with C?O bond scission at the silyloxy-substituted carbon.

Functionalized Benzofurans via Microwave-Promoted Tandem Claisen-Rearrangement/5-endo-dig Cyclization

Ortho-allyloxy alkinyl benzenes undergo, upon microwave irradiation in dimethylformamide, a tandem sequence of Claisen-rearrangement and 5-endo-dig cyclization to furnish 7-allyl-substituted benzofurans. With terminal alkynes, chroman-4-ones and enaminoketones become the main products. A mechanistic proposal for this observation relies on a reaction of the starting material with the solvent dimethylformamide under the microwave conditions.

ALKYNYL-SUBSTITUTED HETEROCYCLIC COMPOUND, PREPARATION METHOD THEREFOR AND MEDICAL USE THEREOF

The present invention relates to an alkynyl-substituted heterocyclic compound acting as an FGFR inhibitor, a preparation method therefor and a medical use thereof. In particular, the present invention relates to a compound as shown in general formula (I) and a pharmaceutically acceptable salt thereof; a pharmaceutical composition including the compound or a pharmaceutically acceptable salt thereof; a method for treating and/or preventing FGFR-associated diseases, particularly tumors, by using the compound or a pharmaceutically acceptable salt thereof; and a preparation method for the compound or a pharmaceutically acceptable salt thereof. The present invention also relates to the use of the compound or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition including the compound or a pharmaceutically acceptable salt thereof in the preparation of a drug for treating and/or preventing FGFR-associated diseases, particularly tumors, wherein the definition of each substituent group in general formula (I) is the same as that in the description.