• Name

  Lapatinib ditosylate

• EINECS 642-915-3
• CAS No. 388082-78-8
• Article Data31
• CAS DataBase
• Density 1.381 g/cm³
• Solubility
• Melting Point 237 - 239 °C
• Formula C₂₉H₂₆ClFN₄O₄S^.2(C₇H₈O₃S)^.H₂O
• Boiling Point 750.7 °C at 760 mmHg
• Molecular Weight 925.477
• Flash Point 407.8 °C
• Transport Information
• Appearance colourless to light-yellow crystal
• Safety
• Risk Codes R43; R51/53
• Molecular Structure
• Hazard Symbols Xi,N
• Synonyms GW572016F;Tykerb;UNII-G873GX646R;Lapatinib ditosylate;
• PSA 249.46000
• LogP 12.26450

Synthetic route

104458-24-4

2-(methylsulfonyl)ethylamine hydrochloride

104-15-4

toluene-4-sulfonic acid

231278-84-5

5-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl)furan-2-carbaldehyde

388082-78-8

lapatinib ditosylate

Conditions

Conditions	Yield
Stage #1: 2-(methylsulfonyl)ethylamine hydrochloride; 5-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl)furan-2-carbaldehyde With tetrabutylammomium bromide; triethylamine In tetrahydrofuran at 30℃; for 3h; Stage #2: With sodium tris(acetoxy)borohydride In tetrahydrofuran at 20℃; for 4h; Stage #3: toluene-4-sulfonic acid In tetrahydrofuran at 50℃; for 1h;	94.9%
Stage #1: 2-(methylsulfonyl)ethylamine hydrochloride; 5-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl)furan-2-carbaldehyde With acetic acid; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 3h; Stage #2: With sodium tris(acetoxy)borohydride In tetrahydrofuran at 20℃; for 12h; Stage #3: toluene-4-sulfonic acid In tetrahydrofuran at 20℃; for 12h;	82.8%
Stage #1: 2-(methylsulfonyl)ethylamine hydrochloride; 5-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl)furan-2-carbaldehyde With acetic acid; N-ethyl-N,N-diisopropylamine In tetrahydrofuran; N,N-dimethyl-formamide at 35℃; for 1h; Stage #2: With sodium tris(acetoxy)borohydride In tetrahydrofuran; N,N-dimethyl-formamide at 20 - 25℃; for 2h; Stage #3: toluene-4-sulfonic acid	72%
Stage #1: 2-(methylsulfonyl)ethylamine hydrochloride; 5-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl)furan-2-carbaldehyde With N-ethyl-N,N-diisopropylamine In tetrahydrofuran; acetic acid at 30 - 35℃; for 1h; Stage #2: With sodium tris(acetoxy)borohydride In tetrahydrofuran; acetic acid at 22℃; for 2 - 4h; Stage #3: toluene-4-sulfonic acid With sodium hydroxide In tetrahydrofuran; acetic acid

...Expand

49773-20-8

2-Methanesulfonyl-ethylamine

104-15-4

toluene-4-sulfonic acid

231278-84-5

5-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl)furan-2-carbaldehyde

388082-78-8

lapatinib ditosylate

Conditions

Conditions	Yield
Stage #1: 2-Methanesulfonyl-ethylamine; 5-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl)furan-2-carbaldehyde In methanol; dichloromethane at 20℃; Stage #2: With hydrogen In methanol; dichloromethane Inert atmosphere; Stage #3: toluene-4-sulfonic acid In methanol; dichloromethane	93%

...Expand

231277-92-2

lapatanib

104-15-4

toluene-4-sulfonic acid

388082-78-8

lapatinib ditosylate

Conditions

Conditions	Yield
In tetrahydrofuran at 20 - 57.5℃;	92.5%
In methanol at 45 - 65℃; Reflux;	88%
In methanol at 25 - 65℃; for 3h;	88%

N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)furan-2-yl]quinazoline-4-amine hydrochloride

104-15-4

toluene-4-sulfonic acid

388082-78-8

lapatinib ditosylate

Conditions

Conditions	Yield
Stage #1: N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)furan-2-yl]quinazoline-4-amine hydrochloride With sodium hydroxide In water; ethyl acetate pH=~ 10; Inert atmosphere; Stage #2: toluene-4-sulfonic acid In N,N-dimethyl-formamide at 40℃; for 1h;	90.1%

1383531-68-7

lapatinib monohydrochloride

104-15-4

toluene-4-sulfonic acid

388082-78-8

lapatinib ditosylate

Conditions

Conditions	Yield
Stage #1: lapatinib monohydrochloride With sodium hydroxide In water; ethyl acetate pH=10; Inert atmosphere; Stage #2: toluene-4-sulfonic acid In N,N-dimethyl-formamide at 40℃; for 1h;	90.1%

49773-20-8

2-Methanesulfonyl-ethylamine

5-(4-[3-chloro-4-(3-fluorobenzyloxy)-anilino]-6-quinazolinyl)-furan-2-carbaldehyde tosylate

104-15-4

toluene-4-sulfonic acid

388082-78-8

lapatinib ditosylate

Conditions

Conditions

Yield

Stage #1: 2-Methanesulfonyl-ethylamine; 5-(4-[3-chloro-4-(3-fluorobenzyloxy)-anilino]-6-quinazolinyl)-furan-2-carbaldehyde tosylate With N-ethyl-N,N-diisopropylamine In tetrahydrofuran; isopropyl alcohol for 1h; Industrial scale; Stage #2: With sodium tris(acetoxy)borohydride; isopropyl alcohol In tetrahydrofuran at 20℃; for 1.66667h; Industrial scale; Stage #3: toluene-4-sulfonic acid Industrial scale; Further stages;

88%

...Expand

903597-10-4

N’-(2-cyano-4-iodophenyl)-N,N-dimethyl formamidine

388082-78-8

lapatinib ditosylate

Conditions

Conditions	Yield
Multi-step reaction with 5 steps 1: acetic acid / 2 h / 115 - 120 °C 2: triethylamine; 1,2-dimethoxyethane / palladium 10% on activated carbon / methanol / Inert atmosphere 3: triethylamine / methanol / 12 h / Reflux 4: methanol / tetrahydrofuran / 0 - 15 °C 5: methanol / 3 h / Reflux View Scheme

27329-70-0

5-formylfurane-2-boronic acid

388082-78-8

lapatinib ditosylate

Conditions

Conditions	Yield
Multi-step reaction with 4 steps 1: triethylamine / palladium 10% on activated carbon / 1,2-dimethoxyethane; methanol / 15 h / 45 - 50 °C / Inert atmosphere 2: triethylamine / methanol / 12 h / Reflux 3: sodium tetrahydroborate / tetrahydrofuran; methanol / 4 h / 10 - 15 °C 4: methanol / 3 h / 25 - 65 °C View Scheme
Multi-step reaction with 3 steps 1.1: triethylamine; palladium / tetrahydrofuran; ethanol / 7 h / 65 °C / Inert atmosphere 2.1: N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 0.33 h / 20 °C 2.2: 2 h / 40 °C 2.3: 3 h / 25 - 40 °C 3.1: tetrahydrofuran / 6 h / 65 °C View Scheme
Multi-step reaction with 3 steps 1.1: palladium 10% on activated carbon / isopropyl methanesulfonate / 0.08 h 1.2: 3 h / 70 °C 3.1: tetrahydrofuran / 4 h / 20 - 55 °C View Scheme
Multi-step reaction with 4 steps 1.1: palladium 10% on activated carbon / isopropyl methanesulfonate / 0.08 h 1.2: 3 h / 70 °C 2.1: isopropyl methanesulfonate; water / 4.08 - 4.17 h / 25 - 65 °C 3.1: acetic acid; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 1 h / 30 - 35 °C 3.2: 2.25 h / 22 - 23 °C 3.3: 0.5 h 4.1: tetrahydrofuran / 4 h / 20 - 55 °C View Scheme

202197-26-0

3-chloro-4-(3-fluorobenzyloxy)aniline

388082-78-8

lapatinib ditosylate

Conditions

Conditions	Yield
Multi-step reaction with 6 steps 1: acetic acid / toluene / 2 h / Reflux 2: acetic acid / xylene / 10 h / Reflux 3: triethylamine / palladium 10% on activated carbon / 1,2-dimethoxyethane; methanol / 15 h / 45 - 50 °C / Inert atmosphere 4: triethylamine / methanol / 12 h / Reflux 5: sodium tetrahydroborate / tetrahydrofuran; methanol / 4 h / 10 - 15 °C 6: methanol / 3 h / 25 - 65 °C View Scheme
Multi-step reaction with 5 steps 1.1: 1-methyl-pyrrolidin-2-one / 0.5 h / 20 - 25 °C 1.2: 0.33 - 0.5 h 2.1: palladium 10% on activated carbon / ethanol; water / 0.08 h 2.2: 3 h / 70 °C 3.1: tetrahydrofuran; ethanol; isopropyl methanesulfonate; water / 2.08 h / 20 - 65 °C 4.1: acetic acid; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 1 h / 30 - 35 °C 4.2: 2 - 4 h / 22 - 23 °C 4.3: 0.5 h 5.1: tetrahydrofuran; water / 3 - 4 h / 20 - 63 °C View Scheme
Multi-step reaction with 5 steps 1.1: tributyl-amine / toluene / 70 - 80 °C 1.2: 2 h / Heating / reflux 2.1: palladium 10% on activated carbon / ethanol; water / 0.08 h 2.2: 3 h / 70 °C 3.1: tetrahydrofuran; ethanol; isopropyl methanesulfonate; water / 2.08 h / 20 - 65 °C 4.1: acetic acid; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 1 h / 30 - 35 °C 4.2: 2 - 4 h / 22 - 23 °C 4.3: 0.5 h 5.1: tetrahydrofuran; water / 3 - 4 h / 20 - 63 °C View Scheme

1227853-05-5

N(1)-(3-chloro-4-(3-fluorobenzyloxy)phenyl)-N,N-dimethylformamidine

388082-78-8

lapatinib ditosylate

Conditions

Conditions	Yield
Multi-step reaction with 5 steps 1: acetic acid / xylene / 10 h / Reflux 2: triethylamine / palladium 10% on activated carbon / 1,2-dimethoxyethane; methanol / 15 h / 45 - 50 °C / Inert atmosphere 3: triethylamine / methanol / 12 h / Reflux 4: sodium tetrahydroborate / tetrahydrofuran; methanol / 4 h / 10 - 15 °C 5: methanol / 3 h / 25 - 65 °C View Scheme

13529-27-6

2-(diethoxymethyl)furan

388082-78-8

lapatinib ditosylate

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1.1: n-butyllithium / 1,2-dimethoxyethane / 2.75 h / -40 - -35 °C / Inert atmosphere 1.2: 2.5 h / -40 - -35 °C 2.1: N-ethyl-N,N-diisopropylamine; acetic acid / tetrahydrofuran / 2 h / 30 - 35 °C 2.2: 3 h / 20 - 25 °C 3.1: Isopropyl acetate / 1 h / 65 - 70 °C View Scheme

16064-08-7

6-iodo-4-hydroxyquinazoline

388082-78-8

lapatinib ditosylate

Conditions

Conditions	Yield
Multi-step reaction with 7 steps 1.1: trifluoroacetic acid / toluene / 110 - 115 °C / Molecular sieve; Inert atmosphere 2.1: potassium carbonate / triphenyl-arsane; tris-(dibenzylideneacetone)dipalladium(0) / N,N-dimethyl-formamide / 2 h / 60 - 65 °C / Inert atmosphere 3.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.5 h / 20 - 35 °C / Inert atmosphere 3.2: 2 h / 20 - 25 °C 4.1: toluene-4-sulfonic acid / methanol / 1 h / 25 °C 5.1: trichlorophosphate / toluene / 0.17 h / 20 °C / Inert atmosphere 5.2: 3 h / 30 - 75 °C 6.1: isopropyl alcohol / 4 h / 70 °C / Inert atmosphere 7.1: sodium hydroxide / ethyl acetate; water / pH ~ 10 / Inert atmosphere 7.2: 1 h / 40 °C View Scheme
Multi-step reaction with 8 steps 1.1: trifluoroacetic acid / toluene / 110 - 115 °C / Molecular sieve; Inert atmosphere 2.1: potassium carbonate / triphenyl-arsane; tris-(dibenzylideneacetone)dipalladium(0) / N,N-dimethyl-formamide / 2 h / 60 - 65 °C / Inert atmosphere 3.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.5 h / 20 - 35 °C / Inert atmosphere 4.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 - 25 °C 5.1: toluene-4-sulfonic acid; methanol / 1 h / 25 °C 6.1: triethylamine; trichlorophosphate / toluene / 3 h / 75 °C / Inert atmosphere 7.1: isopropyl alcohol / 4 h / 70 °C / Inert atmosphere 8.1: sodium hydroxide / ethyl acetate; water / pH 10 / Inert atmosphere 8.2: 1 h / 40 °C View Scheme
Multi-step reaction with 9 steps 1.1: trifluoroacetic acid / toluene / 110 °C / Inert atmosphere 2.1: bis(dibenzylideneacetone)-palladium(0); potassium carbonate; triphenyl-arsane / N,N-dimethyl-formamide / 2 h / 60 - 65 °C / Inert atmosphere 3.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.5 h / 20 - 35 °C / Inert atmosphere 3.2: 2 h / 20 - 25 °C / Inert atmosphere 4.1: triethylamine / N,N-dimethyl-formamide / 1 h / 20 - 55 °C / Inert atmosphere 5.1: sulfuric acid / acetonitrile / 5.25 h / 40 °C / Inert atmosphere 6.1: trichlorophosphate; triethylamine / 1,4-dioxane / 20 - 100 °C / Inert atmosphere 7.1: 1,4-dioxane / 1 h / 55 - 60 °C / Inert atmosphere 8.1: potassium carbonate / 1,4-dioxane; water / 2 h / 55 - 85 °C / Inert atmosphere 9.1: N,N-dimethyl-formamide / 1 h / 35 - 40 °C / Inert atmosphere View Scheme
Multi-step reaction with 9 steps 1.1: trifluoroacetic acid / toluene / 110 °C / Inert atmosphere 2.1: bis(dibenzylideneacetone)-palladium(0); potassium carbonate; triphenyl-arsane / N,N-dimethyl-formamide / 2 h / 60 - 65 °C / Inert atmosphere 3.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.5 h / 20 - 35 °C / Inert atmosphere 3.2: 2 h / 20 - 25 °C / Inert atmosphere 4.1: sulfuric acid; methanol / 2.5 h / 40 - 45 °C / Inert atmosphere 4.2: pH 6-7 5.1: triethylamine / N,N-dimethyl-formamide / 20 - 25 °C / Inert atmosphere 6.1: trichlorophosphate; triethylamine / 1,4-dioxane / 20 - 100 °C / Inert atmosphere 7.1: 1,4-dioxane / 1 h / 55 - 60 °C / Inert atmosphere 8.1: potassium carbonate / 1,4-dioxane; water / 2 h / 55 - 85 °C / Inert atmosphere 9.1: N,N-dimethyl-formamide / 1 h / 35 - 40 °C / Inert atmosphere View Scheme

1383531-71-2

2-(methylsulphonyl)-N-({5-[4-(tetrahydro-2H-pyran-2-yloxy)quinazolin-6-yl]furan-2-yl}methyl)ethanamine

388082-78-8

lapatinib ditosylate

Conditions

Conditions	Yield
Multi-step reaction with 4 steps 1.1: toluene-4-sulfonic acid / methanol / 1 h / 25 °C 2.1: trichlorophosphate / toluene / 0.17 h / 20 °C / Inert atmosphere 2.2: 3 h / 30 - 75 °C 3.1: isopropyl alcohol / 4 h / 70 °C / Inert atmosphere 4.1: sodium hydroxide / ethyl acetate; water / pH ~ 10 / Inert atmosphere 4.2: 1 h / 40 °C View Scheme
Multi-step reaction with 4 steps 1.1: toluene-4-sulfonic acid; methanol / 1 h / 25 °C 2.1: triethylamine; trichlorophosphate / toluene / 3 h / 75 °C / Inert atmosphere 3.1: isopropyl alcohol / 4 h / 70 °C / Inert atmosphere 4.1: sodium hydroxide / ethyl acetate; water / pH 10 / Inert atmosphere 4.2: 1 h / 40 °C View Scheme
Multi-step reaction with 6 steps 1.1: sulfuric acid; methanol / 2.5 h / 40 - 45 °C / Inert atmosphere 1.2: pH 6-7 2.1: triethylamine / N,N-dimethyl-formamide / 20 - 25 °C / Inert atmosphere 3.1: trichlorophosphate; triethylamine / 1,4-dioxane / 20 - 100 °C / Inert atmosphere 4.1: 1,4-dioxane / 1 h / 55 - 60 °C / Inert atmosphere 5.1: potassium carbonate / 1,4-dioxane; water / 2 h / 55 - 85 °C / Inert atmosphere 6.1: N,N-dimethyl-formamide / 1 h / 35 - 40 °C / Inert atmosphere View Scheme
Multi-step reaction with 6 steps 1: triethylamine / N,N-dimethyl-formamide / 1 h / 20 - 55 °C / Inert atmosphere 2: sulfuric acid / acetonitrile / 5.25 h / 40 °C / Inert atmosphere 3: trichlorophosphate; triethylamine / 1,4-dioxane / 20 - 100 °C / Inert atmosphere 4: 1,4-dioxane / 1 h / 55 - 60 °C / Inert atmosphere 5: potassium carbonate / 1,4-dioxane; water / 2 h / 55 - 85 °C / Inert atmosphere 6: N,N-dimethyl-formamide / 1 h / 35 - 40 °C / Inert atmosphere View Scheme

1383531-70-1

5-[4-(tetrahydro-2H-pyran-2-yloxy)quinazolin-6-yl]furan-2-carbaldehyde

388082-78-8

lapatinib ditosylate

Conditions

Conditions	Yield
Multi-step reaction with 5 steps 1.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.5 h / 20 - 35 °C / Inert atmosphere 1.2: 2 h / 20 - 25 °C 2.1: toluene-4-sulfonic acid / methanol / 1 h / 25 °C 3.1: trichlorophosphate / toluene / 0.17 h / 20 °C / Inert atmosphere 3.2: 3 h / 30 - 75 °C 4.1: isopropyl alcohol / 4 h / 70 °C / Inert atmosphere 5.1: sodium hydroxide / ethyl acetate; water / pH ~ 10 / Inert atmosphere 5.2: 1 h / 40 °C View Scheme
Multi-step reaction with 6 steps 1.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.5 h / 20 - 35 °C / Inert atmosphere 2.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 - 25 °C 3.1: toluene-4-sulfonic acid; methanol / 1 h / 25 °C 4.1: triethylamine; trichlorophosphate / toluene / 3 h / 75 °C / Inert atmosphere 5.1: isopropyl alcohol / 4 h / 70 °C / Inert atmosphere 6.1: sodium hydroxide / ethyl acetate; water / pH 10 / Inert atmosphere 6.2: 1 h / 40 °C View Scheme
Multi-step reaction with 7 steps 1.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.5 h / 20 - 35 °C / Inert atmosphere 1.2: 2 h / 20 - 25 °C / Inert atmosphere 2.1: triethylamine / N,N-dimethyl-formamide / 1 h / 20 - 55 °C / Inert atmosphere 3.1: sulfuric acid / acetonitrile / 5.25 h / 40 °C / Inert atmosphere 4.1: trichlorophosphate; triethylamine / 1,4-dioxane / 20 - 100 °C / Inert atmosphere 5.1: 1,4-dioxane / 1 h / 55 - 60 °C / Inert atmosphere 6.1: potassium carbonate / 1,4-dioxane; water / 2 h / 55 - 85 °C / Inert atmosphere 7.1: N,N-dimethyl-formamide / 1 h / 35 - 40 °C / Inert atmosphere View Scheme
Multi-step reaction with 7 steps 1.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.5 h / 20 - 35 °C / Inert atmosphere 1.2: 2 h / 20 - 25 °C / Inert atmosphere 2.1: sulfuric acid; methanol / 2.5 h / 40 - 45 °C / Inert atmosphere 2.2: pH 6-7 3.1: triethylamine / N,N-dimethyl-formamide / 20 - 25 °C / Inert atmosphere 4.1: trichlorophosphate; triethylamine / 1,4-dioxane / 20 - 100 °C / Inert atmosphere 5.1: 1,4-dioxane / 1 h / 55 - 60 °C / Inert atmosphere 6.1: potassium carbonate / 1,4-dioxane; water / 2 h / 55 - 85 °C / Inert atmosphere 7.1: N,N-dimethyl-formamide / 1 h / 35 - 40 °C / Inert atmosphere View Scheme

1334953-74-0

6-[5-({[2-(methylsulphonyl)ethyl]amino}methyl)furan-2-yl]quinazolin-4-ol

388082-78-8

lapatinib ditosylate

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1.1: trichlorophosphate / toluene / 0.17 h / 20 °C / Inert atmosphere 1.2: 3 h / 30 - 75 °C 2.1: isopropyl alcohol / 4 h / 70 °C / Inert atmosphere 3.1: sodium hydroxide / ethyl acetate; water / pH ~ 10 / Inert atmosphere 3.2: 1 h / 40 °C View Scheme
Multi-step reaction with 3 steps 1.1: triethylamine; trichlorophosphate / toluene / 3 h / 75 °C / Inert atmosphere 2.1: isopropyl alcohol / 4 h / 70 °C / Inert atmosphere 3.1: sodium hydroxide / ethyl acetate; water / pH 10 / Inert atmosphere 3.2: 1 h / 40 °C View Scheme
Multi-step reaction with 4 steps 1.1: dmap / tetrahydrofuran / 2.5 h / 25 - 30 °C / Inert atmosphere 2.1: thionyl chloride; N,N-dimethyl-formamide / chloroform / 5.75 h / Reflux; Inert atmosphere 3.1: tetrahydrofuran / 25 - 65 °C / Inert atmosphere 4.1: water; sodium hydroxide / methanol / 2 h / 25 - 30 °C / Reflux 4.2: 3.5 h / 45 - 50 °C / Reflux View Scheme
Multi-step reaction with 5 steps 1: triethylamine / N,N-dimethyl-formamide / 20 - 25 °C / Inert atmosphere 2: trichlorophosphate; triethylamine / 1,4-dioxane / 20 - 100 °C / Inert atmosphere 3: 1,4-dioxane / 1 h / 55 - 60 °C / Inert atmosphere 4: potassium carbonate / 1,4-dioxane; water / 2 h / 55 - 85 °C / Inert atmosphere 5: N,N-dimethyl-formamide / 1 h / 35 - 40 °C / Inert atmosphere View Scheme

1383531-69-8

6-iodo-4-(tetrahydro-2H-pyran-2-yloxy)quinazoline

388082-78-8

lapatinib ditosylate

Conditions

Conditions	Yield
Multi-step reaction with 6 steps 1.1: potassium carbonate / triphenyl-arsane; tris-(dibenzylideneacetone)dipalladium(0) / N,N-dimethyl-formamide / 2 h / 60 - 65 °C / Inert atmosphere 2.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.5 h / 20 - 35 °C / Inert atmosphere 2.2: 2 h / 20 - 25 °C 3.1: toluene-4-sulfonic acid / methanol / 1 h / 25 °C 4.1: trichlorophosphate / toluene / 0.17 h / 20 °C / Inert atmosphere 4.2: 3 h / 30 - 75 °C 5.1: isopropyl alcohol / 4 h / 70 °C / Inert atmosphere 6.1: sodium hydroxide / ethyl acetate; water / pH ~ 10 / Inert atmosphere 6.2: 1 h / 40 °C View Scheme
Multi-step reaction with 7 steps 1.1: potassium carbonate / triphenyl-arsane; tris-(dibenzylideneacetone)dipalladium(0) / N,N-dimethyl-formamide / 2 h / 60 - 65 °C / Inert atmosphere 2.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.5 h / 20 - 35 °C / Inert atmosphere 3.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 - 25 °C 4.1: toluene-4-sulfonic acid; methanol / 1 h / 25 °C 5.1: triethylamine; trichlorophosphate / toluene / 3 h / 75 °C / Inert atmosphere 6.1: isopropyl alcohol / 4 h / 70 °C / Inert atmosphere 7.1: sodium hydroxide / ethyl acetate; water / pH 10 / Inert atmosphere 7.2: 1 h / 40 °C View Scheme
Multi-step reaction with 8 steps 1.1: bis(dibenzylideneacetone)-palladium(0); potassium carbonate; triphenyl-arsane / N,N-dimethyl-formamide / 2 h / 60 - 65 °C / Inert atmosphere 2.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.5 h / 20 - 35 °C / Inert atmosphere 2.2: 2 h / 20 - 25 °C / Inert atmosphere 3.1: sulfuric acid; methanol / 2.5 h / 40 - 45 °C / Inert atmosphere 3.2: pH 6-7 4.1: triethylamine / N,N-dimethyl-formamide / 20 - 25 °C / Inert atmosphere 5.1: trichlorophosphate; triethylamine / 1,4-dioxane / 20 - 100 °C / Inert atmosphere 6.1: 1,4-dioxane / 1 h / 55 - 60 °C / Inert atmosphere 7.1: potassium carbonate / 1,4-dioxane; water / 2 h / 55 - 85 °C / Inert atmosphere 8.1: N,N-dimethyl-formamide / 1 h / 35 - 40 °C / Inert atmosphere View Scheme
Multi-step reaction with 8 steps 1.1: bis(dibenzylideneacetone)-palladium(0); potassium carbonate; triphenyl-arsane / N,N-dimethyl-formamide / 2 h / 60 - 65 °C / Inert atmosphere 2.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.5 h / 20 - 35 °C / Inert atmosphere 2.2: 2 h / 20 - 25 °C / Inert atmosphere 3.1: triethylamine / N,N-dimethyl-formamide / 1 h / 20 - 55 °C / Inert atmosphere 4.1: sulfuric acid / acetonitrile / 5.25 h / 40 °C / Inert atmosphere 5.1: trichlorophosphate; triethylamine / 1,4-dioxane / 20 - 100 °C / Inert atmosphere 6.1: 1,4-dioxane / 1 h / 55 - 60 °C / Inert atmosphere 7.1: potassium carbonate / 1,4-dioxane; water / 2 h / 55 - 85 °C / Inert atmosphere 8.1: N,N-dimethyl-formamide / 1 h / 35 - 40 °C / Inert atmosphere View Scheme

C21H23N3O5S

388082-78-8

lapatinib ditosylate

Conditions

Conditions	Yield
Multi-step reaction with 5 steps 1.1: sodium tris(acetoxy)borohydride / dichloromethane / 2 h / 20 - 25 °C 2.1: toluene-4-sulfonic acid; methanol / 1 h / 25 °C 3.1: triethylamine; trichlorophosphate / toluene / 3 h / 75 °C / Inert atmosphere 4.1: isopropyl alcohol / 4 h / 70 °C / Inert atmosphere 5.1: sodium hydroxide / ethyl acetate; water / pH 10 / Inert atmosphere 5.2: 1 h / 40 °C View Scheme

98556-31-1

4-chloro-6-iodoquinazoline

388082-78-8

lapatinib ditosylate

Conditions

Conditions	Yield
Multi-step reaction with 6 steps 1.1: acetonitrile / 1 h / Reflux 2.1: triethylamine; palladium 10% on activated carbon / water; 1,2-dimethoxyethane; methanol / 45 - 50 °C 3.1: water / 20 - 30 °C 4.1: N-ethyl-N,N-diisopropylamine / methanol / 20 h / 20 - 25 °C 5.1: sodium hydroxide / methanol / 20 h / 20 - 25 °C 6.1: sodium tris(acetoxy)borohydride / tetrahydrofuran / 1 h / 20 - 25 °C 6.3: 3 h View Scheme
Multi-step reaction with 5 steps 1.1: toluene / 1 h / 90 °C 1.2: 5 h / 20 - 72 °C 2.1: N-ethyl-N,N-diisopropylamine / palladium 10% on activated carbon / ethanol / 3 h / 70 °C 3.1: tetrahydrofuran; ethanol; water / 4 h / 25 - 65 °C 4.1: acetic acid; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 1 h / 30 - 35 °C 4.2: 2.25 h / 22 °C 5.1: tetrahydrofuran; water / 3.5 h / 20 - 60 °C View Scheme
Multi-step reaction with 5 steps 1.1: toluene / 1 h / 90 °C 1.2: 3 h / 20 - 72 °C 2.1: N-ethyl-N,N-diisopropylamine / palladium 10% on activated carbon / ethanol / 3 h / 70 °C 3.1: ethanol; water / 4 h / 25 - 65 °C 4.1: acetic acid; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 1 h / 30 - 35 °C 4.2: 2.25 h / 22 °C 5.1: tetrahydrofuran; water / 2.5 h / 60 °C View Scheme

3964-52-1

2-chloro 4-aminophenol

388082-78-8

lapatinib ditosylate

Conditions

Conditions

Yield

Multi-step reaction with 6 steps 1.1: acetonitrile / 1 h / Reflux 2.1: triethylamine; palladium 10% on activated carbon / water; 1,2-dimethoxyethane; methanol / 45 - 50 °C 3.1: water / 20 - 30 °C 4.1: N-ethyl-N,N-diisopropylamine / methanol / 20 h / 20 - 25 °C 5.1: sodium hydroxide / methanol / 20 h / 20 - 25 °C 6.1: sodium tris(acetoxy)borohydride / tetrahydrofuran / 1 h / 20 - 25 °C 6.3: 3 h View Scheme

908332-08-1

2-chloro-4-(6-iodoquinazolin-4-ylamino)phenol

388082-78-8

lapatinib ditosylate

Conditions

Conditions	Yield
Multi-step reaction with 5 steps 1.1: triethylamine; palladium 10% on activated carbon / water; 1,2-dimethoxyethane; methanol / 45 - 50 °C 2.1: water / 20 - 30 °C 3.1: N-ethyl-N,N-diisopropylamine / methanol / 20 h / 20 - 25 °C 4.1: sodium hydroxide / methanol / 20 h / 20 - 25 °C 5.1: sodium tris(acetoxy)borohydride / tetrahydrofuran / 1 h / 20 - 25 °C 5.3: 3 h View Scheme

388082-78-8

lapatinib ditosylate

N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulphonyl)ethyl]amino}methyl)furan-2-yl]quinazolin-4-amine bis(4-methylbenzenesulphonate) monohydrate

Conditions

Conditions	Yield
With water	100%
With water In tetrahydrofuran at 55 - 60℃; for 0.5h;
With water In tetrahydrofuran at 5 - 64℃; for 2.5 - 4h; Heating / reflux;

388082-78-8

lapatinib ditosylate

231277-92-2

lapatanib

Conditions

Conditions	Yield
Stage #1: lapatinib ditosylate In ethyl acetate at 20℃; for 1h; Stage #2: With sodium carbonate In water; ethyl acetate for 1h;	96.2%
With sodium carbonate In water; acetonitrile at 5 - 40℃; for 3.58333h;	91%
With sodium carbonate In water; ethyl acetate at 22 - 70℃; for 3.25h;	56%

Lapatinib ditosylate Chemical Properties

Lapatinib ditosylate Specification