Neratinib supplier | CasNO.698387-09-6

Name
Neratinib
EINECS 811-237-1
CAS No. 698387-09-6
Article Data15
CAS DataBase
Density 1.337 g/cm³
Solubility
Melting Point
Formula C₃₀H₂₉ClN₆O₃
Boiling Point 756.97 °C at 760 mmHg
Molecular Weight 557.052
Flash Point 411.601 °C
Transport Information
Appearance
Safety
Risk Codes
Molecular Structure
Hazard Symbols
Synonyms (E)-N-[4-[3-Chloro-4-[(2-pyridinyl)methoxy]anilino]-3-cyano-7-ethoxy-6-quinolinyl]-4-(dimethylamino)-2-butenamide;(E)-N-[4-[[3-Chloro-4-((pyridin-2-yl)methoxy)phenyl]amino]-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)-2-butenamide;HKI 272;HKI-272(Neratinib);
PSA 112.40000
LogP 6.07848

Synthetic route

: 848139-78-6
6-amino-4-((3-chloro-4-(pyridin-2-ylmethoxy)phenyl)amino)-7-ethoxyquinoline-3-carbonitrile

: 501332-27-0
4-N,N-dimethylaminocrotonoylchloride Hydrochloride

: 698387-09-6
neratinib

Conditions

Conditions	Yield
With sodium hydroxide In 1-methyl-pyrrolidin-2-one; water at 10 - 40℃; for 15h; Solvent;	98%

: 52334-92-6
2-(N,N-dimethylamino)ethoxide

: 1269662-79-4
diethyl ({[4-({3-chloro-4-[(pyridin-2-yl)methoxy]phenyl}amino)-3-cyano-7-ethoxyquinolin-6-yl]carbamoyl}methyl)phosphonate

: 698387-09-6
neratinib

Conditions

Conditions	Yield
Stage #1: diethyl ({[4-({3-chloro-4-[(pyridin-2-yl)methoxy]phenyl}amino)-3-cyano-7-ethoxyquinolin-6-yl]carbamoyl}methyl)phosphonate With sodium ethanolate; lithium chloride In ethanol at -5℃; for 0.5h; Stage #2: 2-(N,N-dimethylamino)ethoxide In ethanol for 0.666667h; Temperature; Solvent; Reagent/catalyst;	95.9%

: 3616-56-6
dimethylaminoacetaldehyde diethyl acetal

: 1269662-79-4
diethyl ({[4-({3-chloro-4-[(pyridin-2-yl)methoxy]phenyl}amino)-3-cyano-7-ethoxyquinolin-6-yl]carbamoyl}methyl)phosphonate

: 698387-09-6
neratinib

Conditions

Conditions	Yield
Stage #1: dimethylaminoacetaldehyde diethyl acetal With hydrogenchloride; water at 0 - 40℃; Inert atmosphere; Stage #2: diethyl ({[4-({3-chloro-4-[(pyridin-2-yl)methoxy]phenyl}amino)-3-cyano-7-ethoxyquinolin-6-yl]carbamoyl}methyl)phosphonate With sodium ethanolate; lithium chloride In ethanol; water at -20℃; for 3h;	95.2%

: 848139-78-6
6-amino-4-((3-chloro-4-(pyridin-2-ylmethoxy)phenyl)amino)-7-ethoxyquinoline-3-carbonitrile

: (2E)-4-(dimethylamino)but-2-enoic acid hydrochloride

: 698387-09-6
neratinib

Conditions

Conditions	Yield
Stage #1: (2E)-4-(dimethylamino)but-2-enoic acid hydrochloride With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 5℃; Inert atmosphere; Stage #2: 6-amino-4-[[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]amino]-7-ethoxyquinoline-3-carbonitrile In 1-methyl-pyrrolidin-2-one; dichloromethane at 10 - 25℃;	95%

: 1269662-79-4
diethyl ({[4-({3-chloro-4-[(pyridin-2-yl)methoxy]phenyl}amino)-3-cyano-7-ethoxyquinolin-6-yl]carbamoyl}methyl)phosphonate

dimethylaminoacetaldehyde-sodium bisulfite adduct: dimethylaminoacetaldehyde-sodium bisulfite adduct

: 698387-09-6
neratinib

Conditions

Conditions	Yield
Stage #1: diethyl ({[4-({3-chloro-4-[(pyridin-2-yl)methoxy]phenyl}amino)-3-cyano-7-ethoxyquinolin-6-yl]carbamoyl}methyl)phosphonate With sodium ethanolate; lithium chloride In ethanol at 0℃; for 0.5h; Stage #2: dimethylaminoacetaldehyde-sodium bisulfite adduct In ethanol for 3h;	94.1%

: 848139-78-6
6-amino-4-((3-chloro-4-(pyridin-2-ylmethoxy)phenyl)amino)-7-ethoxyquinoline-3-carbonitrile

: 1055943-40-2
trans-4-dimethylamino crotonic acid chloride hydrochloride salt

: 698387-09-6
neratinib

Conditions

Conditions	Yield
With triethylamine In tetrahydrofuran at 0 - 10℃; for 1h; Reagent/catalyst; Inert atmosphere;	93%
In 1-methyl-pyrrolidin-2-one at -25 - -20℃; for 5h; Temperature;	86.72%
In tetrahydrofuran; 1-methyl-pyrrolidin-2-one at 0 - 5℃; for 5h; Product distribution / selectivity;	68%

: neratinib maleate

: 698387-09-6
neratinib

Conditions

Conditions	Yield
With sodium hydroxide In methanol	88.7%
With triethylamine In ethanol; acetonitrile at 73℃;

: 524955-09-7
3-chloro-4-(2-pyridylmethoxy)aniline

: 848133-88-0
4-chloro-6-(5-(dimethylamino)-2-oxopent-3-enyl)-7-ethoxyquinoline-3-carbonitrile

: 698387-09-6
neratinib

Conditions

Conditions	Yield
With pyridine hydrochloride In isopropyl alcohol Heating;	85%

: 3964-52-1
2-chloro 4-aminophenol

: 6959-47-3
2-chloromethylpyridine hydrochloride

: 848133-88-0
4-chloro-6-(5-(dimethylamino)-2-oxopent-3-enyl)-7-ethoxyquinoline-3-carbonitrile

: 698387-09-6
neratinib

Conditions

Conditions	Yield
Stage #1: 2-chloro 4-aminophenol; 2-chloromethylpyridine hydrochloride; 4-chloro-6-(5-(dimethylamino)-2-oxopent-3-enyl)-7-ethoxyquinoline-3-carbonitrile In tetrahydrofuran at 65℃; for 6h; Inert atmosphere; Stage #2: With potassium carbonate; potassium iodide In tetrahydrofuran at 60℃; for 16h; Reagent/catalyst; Solvent; Temperature; Inert atmosphere;	82.73%

...Expand

: 4-[4-(2-pyridylmethoxy)-3-chloro]amino-6-amino-3-cyano-7-ethoxyquinoline

: 1056149-69-9
(2E)-(N,N-dimethylamino)-2-butenoyl chloride

: 698387-09-6
neratinib

Conditions

Conditions	Yield
Stage #1: 4-[4-(2-pyridylmethoxy)-3-chloro]amino-6-amino-3-cyano-7-ethoxyquinoline; (2E)-(N,N-dimethylamino)-2-butenoyl chloride With 1-methyl-pyrrolidin-2-one In tetrahydrofuran for 3 - 16h; Stage #2: With water In tetrahydrofuran at 40℃; Stage #3: With sodium hydroxide In tetrahydrofuran; water pH=10 - 11;	80%

: 848139-78-6
6-amino-4-((3-chloro-4-(pyridin-2-ylmethoxy)phenyl)amino)-7-ethoxyquinoline-3-carbonitrile

: 698387-09-6
neratinib

Conditions

Conditions	Yield
Stage #1: (E)-4-(dimethylamino)-2-butenoic acid hydrochloride With oxalyl dichloride; N,N-dimethyl-formamide In tetrahydrofuran at 0 - 30℃; for 2h; Stage #2: 6-amino-4-[[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]amino]-7-ethoxyquinoline-3-carbonitrile In tetrahydrofuran; 1-methyl-pyrrolidin-2-one at 0 - 5℃; for 3 - 16h;	80%

: 848139-78-6
6-amino-4-((3-chloro-4-(pyridin-2-ylmethoxy)phenyl)amino)-7-ethoxyquinoline-3-carbonitrile

: (E)-4-(dimethylamino)-2-butenoic acid hydrochloride

: 698387-09-6
neratinib

Conditions

Conditions	Yield
Stage #1: (E)-4-(dimethylamino)-2-butenoic acid hydrochloride With oxalyl dichloride; N,N-dimethyl-formamide In tetrahydrofuran at 0 - 30℃; for 2.25h; Stage #2: 6-amino-4-[[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]amino]-7-ethoxyquinoline-3-carbonitrile In tetrahydrofuran; 1-methyl-pyrrolidin-2-one at 0 - 10℃; for 20.5h;	52%

: 1056149-69-9
(2E)-(N,N-dimethylamino)-2-butenoyl chloride

: 698387-09-6
neratinib

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1: 7.97 g / 1-methyl-pyrrolidin-2-one / 2.5 h / 0 - 20 °C 2: 85 percent / pyridine hydrochloride / propan-2-ol / Heating View Scheme

: 214476-09-2
4-Chloro-7-ethoxy-6-nitro-quinoline-3-carbonitrile

: 698387-09-6
neratinib

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1: iron; AcOH; NaOAc / methanol / Heating 2: 7.97 g / 1-methyl-pyrrolidin-2-one / 2.5 h / 0 - 20 °C 3: 85 percent / pyridine hydrochloride / propan-2-ol / Heating View Scheme

: 848133-87-9
4-chloro-6-amino-7-ethoxyquinoline-3-carbonitrile

: 698387-09-6
neratinib

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1: 7.97 g / 1-methyl-pyrrolidin-2-one / 2.5 h / 0 - 20 °C 2: 85 percent / pyridine hydrochloride / propan-2-ol / Heating View Scheme

: (E)-4-(dimethylamino)-2-butenoic acid hydrochloride

: 698387-09-6
neratinib

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1: oxalyl chloride; DMF / acetonitrile / 0.5 h / 60 °C 2: 7.97 g / 1-methyl-pyrrolidin-2-one / 2.5 h / 0 - 20 °C 3: 85 percent / pyridine hydrochloride / propan-2-ol / Heating View Scheme

: N-(4-[3-chloro-4-(pyridin-2-ylmethoxy)phenylamino]-3-cyano-7-ethoxyquinoline-6-yl)acetamide

: 698387-09-6
neratinib

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1.1: hydrogenchloride; water / Reflux 2.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 5 h / 40 °C 3.1: hydrogenchloride; water / 0 - 40 °C / Inert atmosphere 3.2: 3 h / -20 °C View Scheme

: 619-08-9
2-chloro-4-nitrophenol

: 698387-09-6
neratinib

Conditions

Conditions	Yield
Multi-step reaction with 6 steps 1.1: potassium carbonate; potassium iodide / N,N-dimethyl-formamide / 12 h / 50 - 60 °C 2.1: iron; ammonium chloride / ethanol; water / 1 h / Reflux 3.1: methanesulfonic acid / ethanol / 2 h / Reflux 4.1: hydrogenchloride; water / Reflux 5.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 5 h / 40 °C 6.1: hydrogenchloride; water / 0 - 40 °C / Inert atmosphere 6.2: 3 h / -20 °C View Scheme

Yield

Multi-step reaction with 6 steps
1.1: potassium carbonate; potassium iodide / N,N-dimethyl-formamide / 12 h / 50 - 60 °C
2.1: iron; ammonium chloride / ethanol; water / 1 h / Reflux
3.1: methanesulfonic acid / ethanol / 2 h / Reflux
4.1: hydrogenchloride; water / Reflux
5.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 5 h / 40 °C
6.1: hydrogenchloride; water / 0 - 40 °C / Inert atmosphere
6.2: 3 h / -20 °C
View Scheme

: 6959-47-3
2-chloromethylpyridine hydrochloride

: 698387-09-6
neratinib

Conditions

Conditions	Yield
Multi-step reaction with 6 steps 1.1: potassium carbonate; potassium iodide / N,N-dimethyl-formamide / 12 h / 50 - 60 °C 2.1: iron; ammonium chloride / ethanol; water / 1 h / Reflux 3.1: methanesulfonic acid / ethanol / 2 h / Reflux 4.1: hydrogenchloride; water / Reflux 5.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 5 h / 40 °C 6.1: hydrogenchloride; water / 0 - 40 °C / Inert atmosphere 6.2: 3 h / -20 °C View Scheme

Yield

: 179687-79-7
2-((2-chloro-4-nitrophenoxy)methyl)pyridine

: 698387-09-6
neratinib

Conditions

Conditions	Yield
Multi-step reaction with 5 steps 1.1: iron; ammonium chloride / ethanol; water / 1 h / Reflux 2.1: methanesulfonic acid / ethanol / 2 h / Reflux 3.1: hydrogenchloride; water / Reflux 4.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 5 h / 40 °C 5.1: hydrogenchloride; water / 0 - 40 °C / Inert atmosphere 5.2: 3 h / -20 °C View Scheme

: 848133-76-6
7-ethoxy-6-acetylamino-4-chloro-quinoline-3-carbonitrile

: 698387-09-6
neratinib

Conditions

Conditions	Yield
Multi-step reaction with 4 steps 1.1: methanesulfonic acid / ethanol / 2 h / Reflux 2.1: hydrogenchloride; water / Reflux 3.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 5 h / 40 °C 4.1: hydrogenchloride; water / 0 - 40 °C / Inert atmosphere 4.2: 3 h / -20 °C View Scheme
Multi-step reaction with 3 steps 1: methanesulfonic acid / N,N-dimethyl-formamide / 70 - 75 °C 2: hydrogenchloride / water / 80 - 85 °C 3: sodium hydroxide / water; 1-methyl-pyrrolidin-2-one / 15 h / 10 - 40 °C View Scheme

: 524955-09-7
3-chloro-4-(2-pyridylmethoxy)aniline

: 698387-09-6
neratinib

Conditions

Conditions	Yield
Multi-step reaction with 4 steps 1.1: methanesulfonic acid / ethanol / 2 h / Reflux 2.1: hydrogenchloride; water / Reflux 3.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 5 h / 40 °C 4.1: hydrogenchloride; water / 0 - 40 °C / Inert atmosphere 4.2: 3 h / -20 °C View Scheme
Multi-step reaction with 3 steps 1: methanesulfonic acid / N,N-dimethyl-formamide / 70 - 75 °C 2: hydrogenchloride / water / 80 - 85 °C 3: sodium hydroxide / water; 1-methyl-pyrrolidin-2-one / 15 h / 10 - 40 °C View Scheme

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1: trifluoroacetic acid / methanol / 4 h / 20 °C / Inert atmosphere 2: platinum on carbon; hydrogen / tetrahydrofuran / 6 h / 25 - 30 °C / 1292.9 Torr 3: triethylamine / tetrahydrofuran / 1 h / 0 - 10 °C / Inert atmosphere View Scheme

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1: sulfuric acid / N,N-dimethyl-formamide / 1 h / 150 °C / Inert atmosphere 2: platinum on carbon; hydrogen / tetrahydrofuran / 6 h / 25 - 30 °C / 1292.9 Torr 3: triethylamine / tetrahydrofuran / 1 h / 0 - 10 °C / Inert atmosphere View Scheme

3-chloro-4-[(pyridin-2-yl)methoxy]-1-p-toluenesulfonyloxybenzene: 3-chloro-4-[(pyridin-2-yl)methoxy]-1-p-toluenesulfonyloxybenzene

: 698387-09-6
neratinib

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1: toluene-4-sulfonic acid / acetonitrile / 6 h / -20 °C / Inert atmosphere 2: platinum on carbon; hydrogen / tetrahydrofuran / 6 h / 25 - 30 °C / 1292.9 Torr 3: triethylamine / tetrahydrofuran / 1 h / 0 - 10 °C / Inert atmosphere View Scheme

: 4-(4-((pyridin-2-yl)methoxy)-3-chloroaniline)-7-ethoxy-6-nitro-3-cyano quinoline

: 698387-09-6
neratinib

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1: platinum on carbon; hydrogen / tetrahydrofuran / 6 h / 25 - 30 °C / 1292.9 Torr 2: triethylamine / tetrahydrofuran / 1 h / 0 - 10 °C / Inert atmosphere View Scheme

: 4-amino-7-ethoxy-3-cyano-6-nitro quinoline

: 698387-09-6
neratinib

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1: sulfuric acid / N,N-dimethyl-formamide / 1 h / 150 °C / Inert atmosphere 2: platinum on carbon; hydrogen / tetrahydrofuran / 6 h / 25 - 30 °C / 1292.9 Torr 3: triethylamine / tetrahydrofuran / 1 h / 0 - 10 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1: trifluoroacetic acid / methanol / 4 h / 20 °C / Inert atmosphere 2: platinum on carbon; hydrogen / tetrahydrofuran / 6 h / 25 - 30 °C / 1292.9 Torr 3: triethylamine / tetrahydrofuran / 1 h / 0 - 10 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1: toluene-4-sulfonic acid / acetonitrile / 6 h / -20 °C / Inert atmosphere 2: platinum on carbon; hydrogen / tetrahydrofuran / 6 h / 25 - 30 °C / 1292.9 Torr 3: triethylamine / tetrahydrofuran / 1 h / 0 - 10 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1: methanesulfonic acid / ethanol / 2 h / 70 °C / Inert atmosphere 2: platinum on carbon; hydrogen / tetrahydrofuran / 6 h / 25 - 30 °C / 1292.9 Torr 3: triethylamine / tetrahydrofuran / 1 h / 0 - 10 °C / Inert atmosphere View Scheme

: 2-((4-bromo-2-chlorophenoxy)methyl)pyridine

: 698387-09-6
neratinib

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1: methanesulfonic acid / ethanol / 2 h / 70 °C / Inert atmosphere 2: platinum on carbon; hydrogen / tetrahydrofuran / 6 h / 25 - 30 °C / 1292.9 Torr 3: triethylamine / tetrahydrofuran / 1 h / 0 - 10 °C / Inert atmosphere View Scheme

: 110-16-7
maleic acid

: 698387-09-6
neratinib

: (2E)-N-[4-[[3-chloro-4-[(pyridin-2-yl)methoxy]phenyl]amino]-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide maleate

Conditions

Conditions	Yield
In ethanol; water at 20℃; for 1h; Inert atmosphere;	98%
With pyrographite In water; acetone at 20 - 40℃; for 0.666667h; Temperature; Solvent;	87.7%
In water; isopropyl alcohol Product distribution / selectivity;	84%

: 698387-09-6
neratinib

: 1376615-55-2
(E)-4-((4-((3-chloro-4-(pyridin-2-ylmethoxy)phenyl)amino)-3-cyano-7-ethoxyquinolin-6-yl)amino)-N,N-dimethyl-4-oxobut-2-en-1-amine oxide

Conditions

Conditions	Yield
Stage #1: neratinib With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 4h; Stage #2: With sodium hydrogencarbonate In dichloromethane; water	10%
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 4h;	10%

: 110-16-7
maleic acid

: 698387-09-6
neratinib

: 1144516-12-0
neratinib maleate monohydrate

Conditions

Conditions	Yield
With water In propan-1-ol at 25 - 60℃; Product distribution / selectivity;

Neratinib Chemical Properties

IUPAC Name: (E)-N-[4-[3-Chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide
Following is the structure of Neratinib (CAS NO.698387-09-6):

Empirical Formula: C₃₀H₂₉ClN₆O₃
Molecular Weight: 557.0427
Index of Refraction: 1.667
Molar Refractivity: 155.073 cm³
Molar Volume: 416.758 cm³
Density: 1.337 g/cm³
Flash Point: 411.601 °C
Polarizability: 61.476 10^-24cm³
Surface Tension: 69.572 dyne/cm
Enthalpy of Vaporization: 110.281 kJ/mol
Boiling Point of Neratinib (CAS NO.698387-09-6): 756.97 °C at 760 mmHg
Canonical SMILES: CCOC1=C(C=C2C(=C1)N=CC(=C2NC3=CC(=C(C=C3)OCC4=CC=CC=N4)Cl)C#N)NC(=O)C=CCN(C)C
Isomeric SMILES: CCOC1=C(C=C2C(=C1)N=CC(=C2NC3=CC(=C(C=C3)OCC4=CC=CC=N4)Cl)C#N)NC(=O)/C=C/CN(C)C
InChI: InChI=1S/C30H29ClN6O3/c1-4-39-28-16-25-23(15-26(28)36-29(38)9-7-13-37(2)3)30(20(17-32)18-34-25)35-21-10-11-27(24(31)14-21)40-19-22-8-5-6-12-33-22/h5-12,14-16,18H,4,13,19H2,1-3H3,(H,34,35)(H,36,38)/b9-7+
InChIKey: JWNPDZNEKVCWMY-VQHVLOKHSA-N

Neratinib Specification

Neratinib , its cas register number 698387-09-6. It also can be called (2E)-N-[4-[[3-chloro-4-[(pyridin-2-yl)methoxy]phenyl]amino]-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide ; HKI 272 ; HKI-272 ; and UNII-JJH94R3PWB .

Product Name

Neratinib

Synthetic route

Neratinib Chemical Properties

Neratinib Specification

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