132131-24-9

Basic information

• Product Name: 2-AMINO-5-IODOBENZONITRILE
• Synonyms: 2-AMINO-5-IODOBENZONITRILE;2-Cyano-4-iodoaniline;2-aminio-5-iodobenzonitrile
• CAS NO: 132131-24-9
• Molecular Formula: C₇H₅IN₂
• Molecular Weight: 244.03247
• Mol File: 132131-24-9.mol
• Article Data: 21

Chemical Properties

• Melting Point: 86℃ (ethanol )
• Boiling Point: 333.622 °C at 760 mmHg
• Flash Point: 155.569 °C
• Appearance: /
• Density: 1.981 g/cm³
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 1.02±0.10(Predicted)
• CAS DataBase Reference: 2-AMINO-5-IODOBENZONITRILE(CAS DataBase Reference)
• NIST Chemistry Reference: 2-AMINO-5-IODOBENZONITRILE(132131-24-9)
• EPA Substance Registry System: 2-AMINO-5-IODOBENZONITRILE(132131-24-9)

Safety Data

• Hazardous Substances Data: 132131-24-9(Hazardous Substances Data)

Usage

Uses

2-Amino-5-iodobenzonitrile is a useful intermediate for the synthesis of lapatinib intermediate of N-[3-chloro-4-3-fluorophenzyloxyphenyl]-6-iodoquinazolin-4-amine.

Synthetic route

anthranilic acid nitrile (1885-29-6) → 5-iodoanthranilonitrile (132131-24-9)

Conditions	Yield
With K(ICl2) In methanol; water at 20℃; for 2h;	93%
With ammonium iodide; dihydrogen peroxide; acetic acid at 20℃; for 12h;	92.6%
With ammonium iodide; dihydrogen peroxide; acetic acid at 20℃; for 12h;	92.6%

N-iodo-succinimide (516-12-1) + anthranilic acid nitrile (1885-29-6) → 5-iodoanthranilonitrile (132131-24-9)

Conditions	Yield
In DMF (N,N-dimethyl-formamide) at 20℃; for 18h;	73%

N-(2-cyano-4-iodo-phenyl)-2,2,2-trifluoro-acetamide → 5-iodoanthranilonitrile (132131-24-9)

Conditions	Yield
With potassium carbonate In methanol at 20℃; for 12h;

N-(2,4-diiodo-phenyl)-2,2,2-trifluoro-acetamide (878133-06-3) → 5-iodoanthranilonitrile (132131-24-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: dimethylformamide / 0.5 h / 100 °C 2: aq. K2CO3 / methanol / 12 h / 20 °C View Scheme

2,4-diiodoaniline (533-70-0) → 5-iodoanthranilonitrile (132131-24-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: dimethylformamide / 0.5 h / 20 °C 2: dimethylformamide / 0.5 h / 100 °C 3: aq. K2CO3 / methanol / 12 h / 20 °C View Scheme

p-aminoiodobenzene (540-37-4) → 5-iodoanthranilonitrile (132131-24-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: ICl / dimethylformamide / 0.5 h / 20 °C 2: dimethylformamide / 0.5 h / 20 °C 3: dimethylformamide / 0.5 h / 100 °C 4: aq. K2CO3 / methanol / 12 h / 20 °C View Scheme

anthranilic acid nitrile (1885-29-6) → 5-iodoanthranilonitrile (132131-24-9) + 3-iodo-2-aminobenzonitrile (114344-67-1)

Conditions	Yield
With dihydrogen peroxide; acetic acid; potassium iodide In water at 20℃; for 24h;

Iodine monochloride (7790-99-0) + anthranilic acid nitrile (1885-29-6) → 5-iodoanthranilonitrile (132131-24-9)

Conditions	Yield
In acetic acid at 25 - 35℃; for 3h;

5-iodoanthranilonitrile (132131-24-9) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → N’-(2-cyano-4-iodophenyl)-N,N-dimethyl formamidine (903597-10-4)

Conditions	Yield
In N,N-dimethyl acetamide at 110℃; for 2h; Product distribution / selectivity; Heating / reflux;	100%
at 70 - 75℃; for 2h;

5-iodoanthranilonitrile (132131-24-9) + N,N-dimethyl-formamide dimethyl acetal (4637-24-5) → (E)-N'-(2-cyano-4-iodophenyl)-N,N-dimethylformamidine

Conditions	Yield
at 120℃; for 2h;	100%
at 90℃; for 1h;	98%
at 90℃; for 1h;	1.2 g

5-iodoanthranilonitrile (132131-24-9) + N,N-dimethyl-formamide dimethyl acetal (4637-24-5) → N’-(2-cyano-4-iodophenyl)-N,N-dimethyl formamidine (903597-10-4)

Conditions	Yield
at 120℃; for 2h;	100%
at 120℃; for 2h;	100%
With acetic acid In toluene at 35℃; for 0.5h;	89.3%
With acetic acid at 35℃; for 0.5h;	89.3%
With acetic acid In toluene at 35℃; for 0.5h;	89.3%

ortho-bromophenylacetic acid (18698-97-0) + 5-iodoanthranilonitrile (132131-24-9) → 2-(2-bromophenyl)-N-(2-cyano-4-iodophenyl)acetamide

Conditions	Yield
Stage #1: ortho-bromophenylacetic acid With thionyl chloride In dichloromethane for 4h; Reflux; Stage #2: 5-iodoanthranilonitrile In toluene for 16h; Reflux;	99%

5-formylfurane-2-boronic acid (27329-70-0) + 5-iodoanthranilonitrile (132131-24-9) → 2-amino-5-[(5-formyl)furan-2-yl]benzonitrile

Conditions	Yield
With palladium 10% on activated carbon; triethylamine In methanol; 1,2-dimethoxyethane at 20 - 45℃; for 3h; Suzuki Coupling;	98.6%

5-formylfurane-2-boronic acid (27329-70-0) + toluene-4-sulfonic acid (104-15-4) + 5-iodoanthranilonitrile (132131-24-9) → 2-amino-5-[(5-formyl)furan-2-yl]benzonitrile p-toluenesulfonic acid

Conditions	Yield
Stage #1: 5-formylfurane-2-boronic acid; 5-iodoanthranilonitrile With palladium 10% on activated carbon; triethylamine In methanol; 1,2-dimethoxyethane at 20 - 45℃; for 3h; Stage #2: toluene-4-sulfonic acid In water at 60℃;	96%

(E)-N'-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)formamidine + 5-iodoanthranilonitrile (132131-24-9) → N-(3-chloro-4-(3-fluorobenzyloxy)phenyl)-6-iodoquinazolin-4-amine (231278-20-9)

Conditions	Yield
With toluene-4-sulfonic acid In toluene at 110℃; for 5h;	92.2%

cyclohexanone (108-94-1) + 5-iodoanthranilonitrile (132131-24-9) → 9-amino-7-iodo-1,2,3,4-tetrahydroacridine (252357-65-6)

Conditions	Yield
Stage #1: cyclohexanone; 5-iodoanthranilonitrile With zinc(II) chloride at 145 - 150℃; for 0.5h; Condensation; Stage #2: With sodium hydroxide In water at 60℃; for 1h; Hydrolysis;	91%
With sodium hydroxide; zinc(II) chloride Multistep reaction;
Stage #1: cyclohexanone; 5-iodoanthranilonitrile With zinc(II) chloride at 140℃; Condensation; Stage #2: With sodium hydroxide Addition;

guanidine hydrochloride (50-01-1) + 5-iodoanthranilonitrile (132131-24-9) → 2,4-diamino-6-iodoquinazoline (132131-20-5)

Conditions	Yield
With sodium ethanolate In ethanol at 80 - 150℃; for 26h;	90%

(methoxymethylidene)dimethylammonium methyl sulfate (21511-55-7, 34643-89-5) + 5-iodoanthranilonitrile (132131-24-9) → N’-(2-cyano-4-iodophenyl)-N,N-dimethyl formamidine (903597-10-4)

Conditions	Yield
With sodium methylate In toluene at 20℃; for 9h;	86.9%

5-iodoanthranilonitrile (132131-24-9) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → 6-Iodo-1H-quinazoline-2,4-dione (16353-27-8)

Conditions	Yield
With zinc(II) chloride at 200℃; for 5h; sealed tube;	80%

acetic anhydride (108-24-7) + 5-iodoanthranilonitrile (132131-24-9) → 2-cyano-4-iodoacetanilide

Conditions	Yield
In acetic acid Heating;	79%

5-iodoanthranilonitrile (132131-24-9) → 2-cyano-4-iodobenzenediazonium tetrafluoroborate

Conditions	Yield
With tert.-butylnitrite; boron trifluoride diethyl etherate In tetrahydrofuran at -20 - 5℃; for 0.5h;	77%

5-iodoanthranilonitrile (132131-24-9) + 4-bromo-benzaldehyde (1122-91-4) + phenylboronic acid (98-80-6) → 2-(4-bromophenyl)-6-iodo-4-phenylquinazoline

Conditions	Yield
With potassium fluoride; 5,5'-dimethyl-2,2'-bipyridine; bis(acetylacetonato)palladium(II); trifluorormethanesulfonic acid In N,N-dimethyl-formamide at 80℃; for 48h; Sealed tube; Schlenk technique;	76%

(E)-N'-(1-(3-fluorobenzyl)-1H-indol-5-yl)-N,N-dimethylformamide + 5-iodoanthranilonitrile (132131-24-9) → N-(1-(3-fluorobenzyl)-1H-indazol-5-yl)-6-iodoquinazolin-4-amine (231278-79-8)

Conditions	Yield
With acetic acid In 5,5-dimethyl-1,3-cyclohexadiene for 10h; Reflux;	75.63%

4-fluoroboronic acid (1765-93-1) + benzaldehyde (100-52-7) + 5-iodoanthranilonitrile (132131-24-9) → 4-(4-fluorophenyl)-6-iodo-2-phenylquinazoline

Conditions	Yield
With potassium fluoride; 5,5'-dimethyl-2,2'-bipyridine; bis(acetylacetonato)palladium(II); trifluorormethanesulfonic acid In N,N-dimethyl-formamide at 80℃; for 48h; Sealed tube; Schlenk technique;	72%

5-iodoanthranilonitrile (132131-24-9) + bis(pinacol)diborane (73183-34-3) → 2‐amino‐5‐(4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolan‐2‐yl)benzonitrile (934426-22-9)

Conditions	Yield
With potassium acetate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride In N,N-dimethyl-formamide at 80℃; for 4h;	69%
With potassium acetate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In N,N-dimethyl-formamide at 80℃; for 4h;	69%

benzaldehyde (100-52-7) + 5-iodoanthranilonitrile (132131-24-9) + phenylboronic acid (98-80-6) → 6-iodo-2,4-diphenylquinazoline

Conditions	Yield
With potassium fluoride; 5,5'-dimethyl-2,2'-bipyridine; bis(acetylacetonato)palladium(II); trifluorormethanesulfonic acid In N,N-dimethyl-formamide at 80℃; for 48h; Sealed tube; Schlenk technique;	68%

4-methyl-benzaldehyde (104-87-0) + 5-iodoanthranilonitrile (132131-24-9) + phenylboronic acid (98-80-6) → 6-iodo-4-phenyl-2-(p-tolyl)quinazoline

Conditions	Yield
With potassium fluoride; 5,5'-dimethyl-2,2'-bipyridine; bis(acetylacetonato)palladium(II); trifluorormethanesulfonic acid In N,N-dimethyl-formamide at 80℃; for 48h; Sealed tube; Schlenk technique;	67%

2-(methoxycarbonyl)benzenediazonium tetrafluoroborate (342-54-1) + 5-iodoanthranilonitrile (132131-24-9) + acetonitrile (75-05-8) → 10-iodo-6-methyl-13H-quinazolino[3,4-a]quinazolin-13-one

Conditions	Yield
at 80℃; for 5h; Sealed tube;	66%

7-(PHENYLSULFONYL)-1H-INDOLE-2-CARBOXYLIC acid (666859-79-6) + 5-iodoanthranilonitrile (132131-24-9) → N-(2-CYANO-4-IODOPHENYL)-7-(PHENYLSULFONYL)-1H-INDOLE-2-carboxamide

Conditions	Yield
Stage #1: 7-(PHENYLSULFONYL)-1H-INDOLE-2-CARBOXYLIC acid With oxalyl dichloride In DMF (N,N-dimethyl-formamide); dichloromethane at 20℃; for 3h; Stage #2: 5-iodoanthranilonitrile In pyridine; dichloromethane at 20℃;	65%

4-Chlorophenylboronic acid (1679-18-1) + benzaldehyde (100-52-7) + 5-iodoanthranilonitrile (132131-24-9) → 4-(4-chlorophenyl)-6-iodo-2-phenylquinazoline

Conditions	Yield
With potassium fluoride; 5,5'-dimethyl-2,2'-bipyridine; bis(acetylacetonato)palladium(II); trifluorormethanesulfonic acid In N,N-dimethyl-formamide at 80℃; for 48h; Sealed tube; Schlenk technique;	65%

5-iodoanthranilonitrile (132131-24-9) + 2-naphthylmethylzinc chloride → 2-amino-5-(2'-naphthylmethyl)benzonitrile (378791-67-4)

Conditions	Yield
dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In tetrahydrofuran for 0.5h; Heating;	63%

5-iodoanthranilonitrile (132131-24-9) + (2-chlorobenzyl)zinc(II) chloride (312624-11-6) → 2-amino-5-(2'-chlorobenzyl)benzonitrile (378791-55-0)

Conditions	Yield
dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In tetrahydrofuran for 0.5h; Heating;	62%

5-iodoanthranilonitrile (132131-24-9) + (2-methoxybenzyl)zinc(II) chloride (312693-15-5) → 2-amino-5-(2'-methoxybenzyl)benzonitrile (378791-60-7)

Conditions	Yield
dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In tetrahydrofuran for 0.5h; Heating;	61%

4-methylphenylboronic acid (5720-05-8) + benzaldehyde (100-52-7) + 5-iodoanthranilonitrile (132131-24-9) → 6-iodo-2-phenyl-4-(p-tolyl)quinazoline

Conditions	Yield
With potassium fluoride; 5,5'-dimethyl-2,2'-bipyridine; bis(acetylacetonato)palladium(II); trifluorormethanesulfonic acid In N,N-dimethyl-formamide at 80℃; for 48h; Sealed tube; Schlenk technique;	61%

5-iodoanthranilonitrile (132131-24-9) + (4-chlorobenzyl)zinc(II) chloride → 2-amino-5-(4'-chlorobenzyl)benzonitrile

Conditions	Yield
dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In tetrahydrofuran for 0.5h; Heating;	59%

5-iodoanthranilonitrile (132131-24-9) + 3,5-dimethoxybenzylzinc chloride → 2-amino-5-(3',5'-dimethoxybenzyl)benzonitrile

Conditions	Yield
dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In tetrahydrofuran for 0.5h; Heating;	59%

Upstream product

• 1885-29-6 anthranilic acid nitrile 
• 878133-06-3 N-(2,4-diiodo-phenyl)-2,2,2-trifluoro-acetamide 
• 533-70-0 2,4-diiodoaniline 
• 540-37-4 p-aminoiodobenzene 
• 516-12-1 N-iodo-succinimide 
• 7790-99-0 Iodine monochloride 

Downstream Products

• 378791-59-4 2-amino-5-(4'-fluorobenzyl)benzonitrile 
• 378791-61-8 2-amino-5-(3'-methoxybenzyl)benzonitrile 
• 378791-55-0 2-amino-5-(2'-chlorobenzyl)benzonitrile 
• 378791-67-4 2-amino-5-(2'-naphthylmethyl)benzonitrile 
• 378791-64-1 2-amino-5-(3',4'-dimethoxybenzyl)benzonitrile 
• 16353-27-8 6-Iodo-1H-quinazoline-2,4-dione 
• 231278-20-9 N-(3-chloro-4-(3-fluorobenzyloxy)phenyl)-6-iodoquinazolin-4-amine 
• 74173-76-5 2,4-dichloro-6-iodoquinazoline 
• 66682-68-6 2-amino-5-benzylbenzonitrile 
• 351425-99-5 2-(2-amino-5-iodophenyl)-4,5-dihydro-1H-imidazole 
• 132131-20-5 2,4-diamino-6-iodoquinazoline 
• 518342-92-2 2-(4-phenylethynyl-3-trifluoromethylphenylethynyl)-5-trimethylsilanylethynylbenzonitrile 
• 518342-88-6 2-phenylethynyl-5-(2-trifluoromethyl-4-trimethylsilanylethynylphenylethynyl)benzonitrile 

Relevant articles and documents

Synthesis of 7-[123I]idotacrine: A potential SPECT agent to map acetylcholinesterase

9-Amino-1,2,3,4-tetrahydroacridine (Tacrine), a cognitive enhancer, is an inhibitor of the enzyme acetylcholinesterase. The synthesis of no-carrier-added 7-[123I]iodotacrine, was accomplished in four steps for potential use in mapping acetylcholinesterase.

2-Cyano-4-iodo-acetanilide: A hydrogen-bonded chain of R 2 2(12) and R22(14) rings

The mol-ecules of 2-cyano-4-iodo-acetanilide, C9H7IN2O, are linked by N - H...N and C - H...O hydrogen bonds into chains of alternating R 2 2(12) and R 2 2(14) rings. International Union of Crystallography 2007.

Novel 4-arylaminoquinazolines bearing N,N-diethyl(aminoethyl)amino moiety with antitumour activity as EGFRwt-TK inhibitor

Herein, four novel 4-arylaminoquinazoline derivatives with N,N-diethyl(aminoethyl)amino moiety were designed, synthesised and evaluated on biological activities in vitro. All synthesised compounds have inhibitory effects against tumour cells (SW480, A549, A431 and NCI-H1975). In particular, 4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(5-((N,N-diethyl(aminoethyl))aminomethyl)furan-2-yl)quinazoline (6a) and 6-(5-((N,N-diethylethyl)aminomethyl)furan-2-yl)-4-(4-(E)-(propen-1-yl)phenylamino)quinazoline (6d) were potent antitumour agents which showed high antiproliferative activities against tumour cells in vitro. Moreover, compound 6a could induce late apoptosis of A549 cells at high concentrations and arrest cell cycle of A549 cells in the G0/G1 phase at tested concentrations. Also, compound 6a could inhibit the activity of wild type epidermal growth factor receptor tyrosine kinase (EGFRwt-TK) with IC50 value of 15.60 nM. Molecular docking showed that compound 6a formed three hydrogen bonds with EGFRwt-TK, while lapatinib formed only two hydrogen bonds with the receptor protein. It is believed that this work would be giving a reference for developing anti-cancer drugs targeted EGFR-TK.

Lapatinib intermediate and its preparation method and application

The invention discloses a lapatinib intermediate as well as a preparation method and application thereof. The lapatinib intermediate contains chemical structures respectively shown in a formula IV, a formula V and a formula VIII (described in the specification). The lapatinib intermediate provided by the invention has the advantages of simple preparation technology, available raw materials, mild reaction conditions, high yield, easy control on quality and the like; by applying the lapatinib intermediate, a preparation route of lapatinib can be shortened, operation is simple, reaction conditions are mild, especially adoption of poisonous reagents such as sulfoxide chloride and phosphorus oxychloride can be avoided, the lapatinib intermediate can be stable in each step, post treatment is simple, yield is high, the lapatinib intermediate is applicable to mass production and has practical value, and large-scale industrial production demand of lapatinib can be met.