7742-73-6

Basic information

• Product Name: 1,3-Dichloroisoquinoline
• Synonyms: 1,3-DICHLOROISOQUINOLINE;TIMTEC-BB SBB003563;4-(AMINOMETHYL)-4-HYDROXY-1-METHYLPIPERIDINE;1,3-Dichloroisoquinoline,97%;isoquinoline, 1,3-dichloro-
• CAS NO: 7742-73-6
• Molecular Formula: C₉H₅Cl₂N
• Molecular Weight: 198.05
• EINECS: 1592732-453-0
• Product Categories: Heterocyclic Series;Quinoline&Isoquinoline;Heterocycle intermediates;Halogenated Heterocycles;Heterocyclic Building Blocks;Isoquinolines;IsoquinolinesBuilding Blocks
• Mol File: 7742-73-6.mol
• Article Data: 11

Chemical Properties

• Melting Point: 121-122 °C(lit.)
• Boiling Point: 307°C(lit.)
• Flash Point: 182.6 °C
• Appearance: white to brown crystalline powder
• Density: 1.407 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.661
• Storage Temp.: Inert atmosphere,Room Temperature
• PKA: -1.49±0.50(Predicted)
• CAS DataBase Reference: 1,3-Dichloroisoquinoline(CAS DataBase Reference)
• NIST Chemistry Reference: 1,3-Dichloroisoquinoline(7742-73-6)
• EPA Substance Registry System: 1,3-Dichloroisoquinoline(7742-73-6)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• Hazardous Substances Data: 7742-73-6(Hazardous Substances Data)

Usage

Chemical Properties

White to brown crystalline powder

Uses

1,3-Dichloroisoquinoline may be used in the facile synthesis of 1,3,4-trisubstituted isoquinoline derivatives.

General Description

1,3-Dichloroisoquinoline undergoes Pd(PPh3)4 catalyzed regioselective coupling with arylboronic acids to afford to 1-aryl-3-chloroisoquinolines. Reaction of amine with 1,3-dichloroisoquinoline has been studied. Regioselectivity of the Stille coupling reaction of (1-ethoxyvinyl)tri(n-butyl)stannane with 1,3-dichloroisoquinoline has been investigated.

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 
• 13331-23-2 fur-2-ylboronic acid 
• 1168136-15-9 1,3‐dichloro‐4‐iodoisoquinoline 
• 824-72-6 P,P-dichlorophenylphosphine oxide 
• 4456-77-3 4H-isoquinolin-1,3-dione 
• 6627-91-4 2-cyanomethylbenzoic acid 
• 89-51-0 Homophthalic acid 

Downstream Products

• 24649-22-7 1-Chloro-3-methoxyisoquinoline 
• 119-65-3 isoquinoline 
• 19493-45-9 3-chloroisoquinoline 
• 7742-74-7 3-chloro-1-hydroxyisoquinoline 
• 91-21-4 1,2,3,4-tetrahydroisoquinoline 
• 190188-42-2 3-chloro-1-(4-tolyl)isoquinoline 
• 190188-43-3 1-(2-methoxyphenyl)-3-chloroisoquinoline 
• 89721-07-3 3-chloro-1-phenylisoquinoline 
• 928162-16-7 (S)-tert-butoxycarbonylamino[4-(3-chloroisoquinolin-1-yloxy)phenyl]acetic acid 
• 928162-17-8 (S)-tert-butoxycarbonylamino[4-(3-pyridin-4-ylisoquinolin-1-yloxy)phenyl]acetic acid 
• 928162-31-6 C₃₆H₃₇N₅O₇S 
• 928162-50-9 C₃₅H₃₆N₄O₆ 
• 928162-53-2 C₄₄H₅₁N₅O₇ 
• 10296-47-6 3-chloro-5-nitro-isoquinoline 

Relevant articles and documents

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%).

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.

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