7742-73-6

Usage

Uses

Used in Pharmaceutical Synthesis:
1,3-Dichloroisoquinoline is used as a key intermediate for the synthesis of 1,3,4-trisubstituted isoquinoline derivatives, which are important in the development of pharmaceuticals with potential therapeutic applications. Its reactivity allows for the facile introduction of various functional groups, enabling the creation of a wide range of bioactive compounds.
Used in Organic Chemistry:
In the field of organic chemistry, 1,3-Dichloroisoquinoline serves as a versatile building block for the synthesis of complex organic molecules. Its ability to undergo various chemical reactions, such as nucleophilic substitution and cross-coupling, makes it a valuable component in the construction of diverse chemical libraries and the development of novel organic materials.

InChI:InChI=1/C9H5Cl2N/c10-8-5-6-3-1-2-4-7(6)9(11)12-8/h1-5H

Synthetic route

2-cyanomethylbenzoic acid (6627-91-4) → 1,3-dichloroisoquinoline (7742-73-6)

Conditions	Yield
With phosphorus pentachloride; trichlorophosphate In 2-cyanomethylbenzoic acid at 20 - 70℃; for 17.5h;	84.5%

4H-isoquinolin-1,3-dione (4456-77-3) → 1,3-dichloroisoquinoline (7742-73-6)

Conditions	Yield
With P,P-dichlorophenylphosphine oxide at 130℃; for 2h;	79%
With P,P-dichlorophenylphosphine oxide In tetrahydrofuran; water at 20 - 160℃;	74%
With P,P-dichlorophenylphosphine oxide at 160℃; for 3h; neat;	6.75 g
With P,P-dichlorophenylphosphine oxide	9.30 g
With P,P-dichlorophenylphosphine oxide at 160℃; for 4h;

Homophthalic acid (89-51-0) → 1,3-dichloroisoquinoline (7742-73-6)

Conditions	Yield
Stage #1: Homophthalic acid With ammonium hydroxide Heating; Stage #2: With P,P-dichlorophenylphosphine oxide at 160℃; for 3h;	75%
Multi-step reaction with 2 steps 1.1: aq. NH3 / Heating 1.2: 1,2-dichloro-benzene / 3 h / 200 °C 2.1: 6.75 g / dichlorophenylphosphine oxide / 3 h / 160 °C / neat View Scheme

isoquinoline-1,3-diol (86-94-2) → 1,3-dichloroisoquinoline (7742-73-6)

Conditions	Yield
With P,P-dichlorophenylphosphine oxide at 160℃;

2-phenethyl-4H-isoquinoline-1,3-dione (53558-67-1) + trichlorophosphate (10025-87-3, 12599-09-6, 63736-95-8) → 1,3-dichloroisoquinoline (7742-73-6)

Conditions	Yield
at 140 - 150℃;

1.3-dioxy-isoquinoline → 1-chloroisoquinolin-3-ol (53093-78-0) + 1,3-dichloroisoquinoline (7742-73-6)

Conditions	Yield
With trichlorophosphate at 150 - 170℃;

4H-isoquinolin-1,3-dione (4456-77-3) → 1,3-dichloroisoquinoline (7742-73-6) + 1-chloro-3-oxy-isoquinoline

Conditions	Yield
With trichlorophosphate at 150 - 170℃; im Rohr;

isoquinoline-1,3-diol (86-94-2) + trichlorophosphate (10025-87-3, 12599-09-6, 63736-95-8) → 1,3-dichloroisoquinoline (7742-73-6) + 1-chloro-3-oxy-isoquinoline

Conditions	Yield
at 150 - 170℃;

P,P-dichlorophenylphosphine oxide (824-72-6) + isoquinoline-13 (2H4H)-dione → 1,3-dichloroisoquinoline (7742-73-6)

Conditions	Yield
In tetrahydrofuran; water

P,P-dichlorophenylphosphine oxide (824-72-6) + 4H-isoquinolin-1,3-dione (4456-77-3) → 1,3-dichloroisoquinoline (7742-73-6)

Conditions	Yield
In tetrahydrofuran; water
In tetrahydrofuran; water

fur-2-ylboronic acid (13331-23-2) + 1,3‐dichloro‐4‐iodoisoquinoline (1168136-15-9) → 1,3-dichloroisoquinoline (7742-73-6) + C13H7Cl2NO (1168136-22-8)

Conditions	Yield
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate In 1,3-dioxane; water at 75℃; for 12h; Suzuki coupling;

1,3-dichloroisoquinoline (7742-73-6) → (3-chloro-isoquinolin-1-yl)-acetic acid tert-butyl ester (1402816-06-1)

Conditions	Yield
Stage #1: acetic acid tert-butyl ester With n-butyllithium; 1,1,1,3,3,3-hexamethyl-disilazane; tris-(dibenzylideneacetone)dipalladium(0); DavePhos In toluene at -78 - 20℃; for 1.25h; Stage #2: 1,3-dichloroisoquinoline In toluene at 20℃; for 0.5h;	100%

1,3-dichloroisoquinoline (7742-73-6) + (2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid (13726-69-7) → C19H21ClN2O5 (630425-54-6)

Conditions	Yield
Stage #1: (2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid With sodium hydride In DMF (N,N-dimethyl-formamide) at 0℃; for 0.5h; Stage #2: 1,3-dichloroisoquinoline In DMF (N,N-dimethyl-formamide) at 20℃; for 12h;	99.8%

1,3-dichloroisoquinoline (7742-73-6) + 1-amino-3-(dimethylamino)propane (109-55-7) → N1-(3-chloro-1-isoquinolinyl)-N3,N3-dimethyl-1,3-propanediamine dihydrochloride

Conditions	Yield
Stage #1: 1,3-dichloroisoquinoline; 1-amino-3-(dimethylamino)propane for 0.5h; Heating / reflux; Stage #2: With hydrogenchloride In methanol	99%

1,3-dichloroisoquinoline (7742-73-6) + N-tert-butyloxycarbonyl-L-4-hydroxyphenylglycine (69651-48-5) → (S)-tert-butoxycarbonylamino[4-(3-chloroisoquinolin-1-yloxy)phenyl]acetic acid (928162-16-7)

Conditions	Yield
With potassium tert-butylate In dimethyl sulfoxide at 40℃; for 336h;	99%

1,3-dichloroisoquinoline (7742-73-6) + 2-methoxynaphthalene-1-boronic acid (104116-17-8) → 3-chloro-1-(2-methoxylnaphthalen-1-yl)isoquinoline (190188-44-4)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); cesium fluoride In 1,2-dimethoxyethane at 90℃; Suzuki-Miyaura Coupling; regioselective reaction;	96%
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,2-dimethoxyethane; ethanol at 90℃; for 120h; Suzuki-Miyaura Coupling; regioselective reaction;	86%
With cesium fluoride; tetrakis(triphenylphosphine) palladium(0) In 1,2-dimethoxyethane for 6h; Heating;	85%
With cesium fluoride; tetrakis(triphenylphosphine) palladium(0) In 1,2-dimethoxyethane at 90℃; for 18h; Suzuki cross-coupling;	79%

methanol (67-56-1) + 1,3-dichloroisoquinoline (7742-73-6) → 1-Chloro-3-methoxyisoquinoline (24649-22-7)

Conditions	Yield
With sodium In acetonitrile at 65℃; for 1.5h;	94%

1,3-dichloroisoquinoline (7742-73-6) → 3-chloroisoquinoline-1-d

Conditions	Yield
With C60H48BP3Pd; potassium deuteroformate; [2.2.2]cryptande In tetrahydrofuran at 60℃; for 72h; Schlenk technique; Inert atmosphere;	94%

1,3-dichloroisoquinoline (7742-73-6) + sodium methylate (124-41-4) → 1-Chloro-3-methoxyisoquinoline (24649-22-7)

Conditions	Yield
In 1,4-dioxane at 65℃;	92.2%

1,3-dichloroisoquinoline (7742-73-6) → 1,3-dichloro-5-nitroisoquinoline (18203-64-0)

Conditions	Yield
With sulfuric acid; nitric acid at 0 - 25℃;	91%
With sulfuric acid; nitric acid In water at 0 - 5℃; for 2h;	91%
With sulfuric acid; nitric acid at 0 - 25℃; for 16.5h;	81%

1,3-dichloroisoquinoline (7742-73-6) + methylmagnesium bromide (75-16-1) → 3-chloro-1-methylisoquinoline (15787-12-9)

Conditions	Yield
With iron(III)-acetylacetonate In tetrahydrofuran; toluene at 0℃; for 2h; Inert atmosphere; chemoselective reaction;	91%

1,3-dichloroisoquinoline (7742-73-6) + phenylboronic acid (98-80-6) → 3-chloro-1-phenylisoquinoline (89721-07-3)

Conditions	Yield
With cesium fluoride; tetrakis(triphenylphosphine) palladium(0) In 1,2-dimethoxyethane for 6h; Heating;	90%
With tetrakis(triphenylphosphine) palladium(0); cesium fluoride In Dimethyl ether at 85℃; for 36h; Inert atmosphere;	60%
With tetrakis(triphenylphosphine) palladium(0); cesium fluoride In 1,2-dimethoxyethane for 48h; Suzuki-Miyaura Coupling; Inert atmosphere; Reflux;	56%

1,3-dichloroisoquinoline (7742-73-6) + N-aminopyridin-1-ium iodide (6295-87-0) → N-(3-chloroisoquinolin-1-yl)pyridinium aminide (1051915-84-4)

Conditions	Yield
With potassium carbonate In acetonitrile for 6h; Heating;	90%

1,3-dichloroisoquinoline (7742-73-6) → 1,3‐dichloro‐4‐iodoisoquinoline (1168136-15-9)

Conditions	Yield
Stage #1: 1,3-dichloroisoquinoline With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.25h; Stage #2: With iodine In tetrahydrofuran at 20℃;	90%
With iodine; lithium diisopropyl amide In tetrahydrofuran at -78℃;

1,3-dichloroisoquinoline (7742-73-6) + adamantylmethylamine (17768-41-1) → N-(1-adamantylmethyl)-3-chloroisoquinolin-1-amine

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 140℃; for 24h; Inert atmosphere;	90%

1,3-dichloroisoquinoline (7742-73-6) + potassium tert-butylate (865-47-4) → 1-tert-butoxy-3-chloroisoquinoline (1241384-74-6)

Conditions	Yield
In toluene at 80℃; for 3h;	89.1%
In toluene Reflux;	89%

1,3-dichloroisoquinoline (7742-73-6) + 2-(adamantan-1-yloxy)ethan-1-amine (25225-13-2) → N-[2-(1-adamantyloxy)ethyl]-3-chloroisoquinolin-1-amine

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 140℃; for 24h; Inert atmosphere;	89%
With potassium carbonate In N,N-dimethyl-formamide at 140℃; for 24h; Activation energy;	89%

1,3-dichloroisoquinoline (7742-73-6) → C9H4(2)HCl2N (1168136-27-3)

Conditions	Yield
Stage #1: 1,3-dichloroisoquinoline With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 2h; Stage #2: With water-d2; hydrogen chloride In tetrahydrofuran	88%

1,3-dichloroisoquinoline (7742-73-6) + 4-methylphenylboronic acid (5720-05-8) → 3-chloro-1-(4-tolyl)isoquinoline (190188-42-2)

Conditions	Yield
With cesium fluoride; tetrakis(triphenylphosphine) palladium(0) In 1,2-dimethoxyethane for 6h; Heating;	87%

1-iodo-2-methyl-2-propene (3756-30-7) + 1,3-dichloroisoquinoline (7742-73-6) → C13H11Cl2N (1168136-13-7)

Conditions	Yield
Stage #1: 1,3-dichloroisoquinoline With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.25h; Stage #2: 1-iodo-2-methyl-2-propene In tetrahydrofuran at 20℃;	87%

1,3-dichloroisoquinoline (7742-73-6) + allyl iodid (556-56-9) → 4-allyl-1,3-dichloroisoquinoline (1168136-12-6)

Conditions	Yield
Stage #1: 1,3-dichloroisoquinoline With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.25h; Stage #2: allyl iodid In tetrahydrofuran at 20℃;	87%

1,3-dichloroisoquinoline (7742-73-6) + (S)-1-Pyrrolidin-2-yl-methanol (23356-96-9) → (S)-(1-(3-chloroisoquinolin-1-yl)pyrrolidin-2-yl)methanol

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In isopropyl alcohol at 115℃; for 1h; Microwave irradiation;	87%

1,3-dichloroisoquinoline (7742-73-6) + 2-methyl-1-naphthylboronic acid (103989-84-0) → 3-chloro-1-(2-methylnaphthalen-1-yl)isoquinoline (1394249-29-6)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); cesium fluoride In 1,2-dimethoxyethane at 90℃; Suzuki-Miyaura Coupling; regioselective reaction;	83%
With tetrakis(triphenylphosphine) palladium(0); cesium fluoride In 1,2-dimethoxyethane Suzuki Coupling; Reflux;	82%
With tetrakis(triphenylphosphine) palladium(0) In 1,2-dimethoxyethane at 90℃; for 48h; Suzuki-Miyaura Coupling; regioselective reaction;	81%

1,3-dichloroisoquinoline (7742-73-6) + benzaldehyde, hydrazone (5281-18-5) → C16H12ClN3 (1258543-03-1)

Conditions	Yield
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate In toluene at 100 - 104℃; for 2.5h; Inert atmosphere;	81%
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate In toluene at 100℃; Inert atmosphere;	81%

1,3-dichloroisoquinoline (7742-73-6) + methyl trifluoromethanesulfonate (333-27-7) → 1,3-dichloro-4-methyl-isoquinoline (15787-23-2)

Conditions	Yield
Stage #1: 1,3-dichloroisoquinoline With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.25h; Stage #2: methyl trifluoromethanesulfonate In tetrahydrofuran at 20℃;	80%

1,3-dichloroisoquinoline (7742-73-6) + mesitylboronic acid (5980-97-2) → 3-chloro-1-mesitylisoquinoline

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); cesium fluoride In 1,2-dimethoxyethane for 24h; Inert atmosphere; Reflux;	78%

1,3-dichloroisoquinoline (7742-73-6) → 4-(1-isoquinolyl)-1-piperazinecarboxylic acid tert-butyl ester (205264-33-1)

Conditions	Yield
	77%

1,3-dichloroisoquinoline (7742-73-6) + (S)-3-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester (101469-92-5) → (S)-tert-butyl 3-((3-chloroisoquinolin-1-yl)oxy)pyrrolidine-1-carboxylate

Conditions	Yield
Stage #1: (S)-3-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester With sodium hydride In 1-methyl-pyrrolidin-2-one at 0℃; for 0.0833333h; Stage #2: 1,3-dichloroisoquinoline In 1-methyl-pyrrolidin-2-one at 20 - 135℃; for 0.583333h; Microwave irradiation;	75%

Upstream product

• 86-94-2 isoquinoline-1,3-diol 
• 53558-67-1 2-phenethyl-4H-isoquinoline-1,3-dione 
• 10025-87-3 trichlorophosphate 
• 4456-77-3 4H-isoquinolin-1,3-dione 
• 824-72-6 P,P-dichlorophenylphosphine oxide 
• 13331-23-2 fur-2-ylboronic acid 
• 1168136-15-9 1,3‐dichloro‐4‐iodoisoquinoline 
• 6627-91-4 2-cyanomethylbenzoic acid 
• 89-51-0 Homophthalic acid 

Downstream Products

• 190188-42-2 3-chloro-1-(4-tolyl)isoquinoline 
• 190188-43-3 1-(2-methoxyphenyl)-3-chloroisoquinoline 
• 89721-07-3 3-chloro-1-phenylisoquinoline 
• 119-65-3 isoquinoline 
• 19493-45-9 3-chloroisoquinoline 
• 928162-16-7 (S)-tert-butoxycarbonylamino[4-(3-chloroisoquinolin-1-yloxy)phenyl]acetic acid 
• 861959-43-5 1-(2-methoxynaphthalen-1-yl)-3-(2-methoxyphenyl)isoquinoline 
• 861959-42-4 1-[3-(2-hydroxyphenyl)isoquinolin-1-yl]naphthalen-2-ol 
• 58022-21-2 1-acetylisoquinoline 
• 205264-33-1 4-(1-isoquinolyl)-1-piperazinecarboxylic acid tert-butyl ester 
• 1168136-14-8 C₁₆H₉Cl₂NO 
• 1258543-03-1 C₁₆H₁₂ClN₃ 
• 1309868-72-1 3-chloro-1-(4-tosylpiperazin-1-yl)isoquinoline 
• 95702-58-2 1,3-diphenylisoquinolin-2-ium chloride 

Relevant academic research and scientific papers

Axially chiral tridentate isoquinoline derived ligands for diethylzinc addition to aldehydes

The synthesis and resolution of new tridentate isoquinoline-derived ligands has been developed. The key steps in the synthetic sequence include successive, chemo-selective Suzuki-Miyaura cross-couplings of 1,3-dichloroisoquinoline with suitable arylboronic acids. The new ligands prepared in this manner were resolved either via molecular complexation with N-benzylcinchonidinium chloride as with 1-[3-(2-hydroxyphenyl)isoquinolin-1-yl]naphthalen-2-ol or via chromatographic separation of its epimeric camphorsulfonates as for 1,3-bis-(2-hydroxynaphthalen-1-yl)isoquinoline. 4-tert-Butyl-2-chloro-6-[1-(2-hydroxymethylnaphthalen-1-yl)isoquinolin-3-yl]phenol was resolved by chiral semi-preparative HPLC. The application of these ligands in the diethylzinc addition to aldehydes was investigated. In certain cases, the desired secondary alcohols were obtained in high yield with excellent enantiomeric excess (ee > 99%) at low catalyst loading (1 mol%).

SUBSTITUTED AROMATIC CARBOXAMIDE AND UREA DERIVATIVES AS VANILLOID RECEPTOR LIGANDS

The invention relates to substituted aromatic carboxamide and urea derivatives, to processes for the preparation thereof, to pharmaceutical compositions containing these compounds and also to the use of these compounds for preparing pharmaceutical compositions (formula (I)).

A facile synthesis of 1,3,4-trisubstituted isoquinolines

A facile and versatile approach to 1,3,4-trisubstituted isoquinoline derivatives from commercially available 1,3-dichloroisoquinoline is described.

In vitro structure-activity relationship and in vivo characterization of 1-(aryl)-3-(4-(amino)benzyl)urea transient receptor potential vanilloid 1 antagonists

The synthesis and structure-activity relationship of 1-(aryl)-3-(4-(amino) benzyl)urea transient receptor potential vanilloid 1 (TRPV1) antagonists are described. A variety of cyclic amine substituents are well tolerated at the 4-position of the benzyl group on compounds containing either an isoquinoline or indazole heterocyclic core. These compounds are potent antagonists of capsaicin activation of the TRPV1 receptor in vitro. Analogues, such as compound 45, have been identified that have good in vivo activity in animal models of pain. Further optimization of 45 resulted in compound 58 with substantially improved microsome stability and oral bioavailability, as well as in vivo activity.

Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor

Compounds of formula (I) are novel VR1 antagonists that are useful in treating pain, inflammatory thermal hyperalgesia, urinary incontinence and bladder overactivity, wherein X1, X2, X3, X4, X5, R5, R6, R7, R8a, R8b, R9, Z1, Z2 and L are as defined in the description.

Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor

Compounds of formula (I) are novel VR1 antagonists that are useful in treating pain, inflammatory thermal hyperalgesia, urinary incontinence and bladder overactivity.

Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor

Compounds of formula (I) are novel VR1 antagonists that are useful in treating pain, inflammatory thermal hyperalgesia, urinary incontinence and bladder overactivity.

Hydroformylation

The present invention relates to a process for hydroformylating in the presence of a catalyst comprising at least one complex of a metal of transition group VIII with mono-phosphorus compounds which are capable of dimerizing via noncovalent bonds as ligands, to such catalysts and to their use.

Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor

Compounds of formula (I) are novel VR1 antagonists that are useful in treating pain, inflammatory thermal hyperalgesia, urinary incontinence and bladder overactivity.

Fused pyridine derivatives

The present provides a condensed pyridine compound (I) represented by the following formula: (wherein, R2represents ring A represents benzene ring, pyridine ring, thiophene ring or furan ring; and B represents its pharmaceutically acceptable salt or hydrates thereof, which is a clinically useful medicament having a serotonin antagonism, in particular, that for treating, ameliorating or preventing spastic paralysis or central muscle relaxants for ameliorating myotonia.