104458-24-4

Basic information

• Product Name: 2-Aminoethylmethylsulfone hydrochloride
• Synonyms: 2-MESYLETHAN-1-AMINE HYDROCHLORIDE;2-(Methylsulfonyl)-ethanamine hydrochloride;2-(Methylsulfonyl)Ethylamine HCl;2-(methylsulfonyl)ethylamine hydrochloride;2-Aminoethylmethylsulfone hydrochloride;2-(METHANE SULFONYL)ETHYLAMINE HYDROCHLORIDE;2-(Methylsulfonyl)ethanamine hydrochloride ,95%;Lapatinib Intermediate 1
• CAS NO: 104458-24-4
• Molecular Formula: C₃H₉NO₂S*ClH
• Molecular Weight: 159.63
• EINECS: 1806241-263-5
• Product Categories: Intermediate of lapatinib ditosylate;Lapatinib
• Mol File: 104458-24-4.mol
• Article Data: 8

Chemical Properties

• Melting Point: 168.0 to 172.0 °C
• Boiling Point: 325.8 °C at 760 mmHg
• Flash Point: 150.8 °C
• Appearance: power
• Vapor Pressure: 0.000163mmHg at 25°C
• Storage Temp.: Room temperature.
• Solubility: DMSO (Slightly, Sonicated), Methanol (Slightly, Sonicated)
• Stability: Hygroscopic
• CAS DataBase Reference: 2-Aminoethylmethylsulfone hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Aminoethylmethylsulfone hydrochloride(104458-24-4)
• EPA Substance Registry System: 2-Aminoethylmethylsulfone hydrochloride(104458-24-4)

Safety Data

• Hazardous Substances Data: 104458-24-4(Hazardous Substances Data)

Usage

Description

Lapatinib is a new drug targeted for the treatment of breast cancer developed by GlaxoSmithKline, which was approved for marketing by the US Food and Drug Administration on March 13, 2007. The currently approved indications are advanced mastocarcinoma treated with lapatinib and capecitabine or metastatic breast cancer, and breast cancer patients must be treated first in other first-class drugs. Its trade name is Tykerb in the United States. On December 14, 2007, the European Medicines Agency (EMEA) approved for marketing of lapatinib in Europe, and the trade name is Tyverb. Breast cancer molecular targeted therapy is the treatment for oncogene related with occurrence and development of breast cancer, and for its related expression product. Molecular targeted drugs control the changes of gene expression in the cell through blocking signal transduction of tumor cell or related cell, thereby inhibiting or killing tumor cells. Lapatinib is a small molecule epidermal growth factor tyrosine kinase inhibitor orally. Clinical trials have shown that lapatinib has a very good clinical effect in patients with HER2 breast cancer who have been resistant to Roche's Herceptin. In vitro, the inhibitory effect of lapatinib on the growth of Her-2 overexpressing breast cancer cell lines was significant. Lapatinib is also highly effective in the Phase I clinical trial of Her-2 overexpression in advanced breast cancer and has no cross-resistance with Herceptin (trastuzumab). Unlike Herceptin (trastuzumab), its structure is small molecules, so it could get through the blood-brain barrier, thereby having a certain therapeutic effect for breast cancer brain metastases.

Chemical Properties

Off-white to yellow solid

Uses

2-(Methylsulfonyl)ethylamine Hydrochloride is used in the synthetic preparation of potent and selective PI3Kδ inhibitors.

InChI:InChI=1/C3H9NO2S.ClH/c1-7(5,6)3-2-4;/h2-4H2,1H3;1H

Synthetic route

tert-butyl 2-(methylsulfonyl)ethylcarbamate (154095-06-4) → 2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4)

Conditions	Yield
With hydrogenchloride In ethyl acetate at 0 - 20℃;	97%
With hydrogenchloride In ethanol at 20℃; Temperature;	88%
With hydrogenchloride In diethyl ether; ethyl acetate at 20℃;	78%

(2-aminoethyl)methylsulfide (18542-42-2) → 2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4)

Conditions	Yield
With hydrogenchloride; dihydrogen peroxide In water at 25 - 30℃; pH=3 - 4; Solvent;	94.8%

2-<2-(methylsulfonyl)ethyl>-1H-isoindole-1,3(2H)dione → 2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4)

Conditions	Yield
With hydrogenchloride; water at 100℃; for 10h; Reagent/catalyst; Temperature;	92.1%
With hydrogenchloride In water at 100℃; for 10h;	92.1%

hydrochloride of methyl-<β-amino-ethyl>-sulfide → 2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4)

Conditions	Yield
With potassium permanganate; water

2-Methanesulfonyl-ethylamine (49773-20-8) → 2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4)

Conditions	Yield
With hydrogenchloride In ethanol Product distribution / selectivity;

2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4) + 5-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl)furan-2-carbaldehyde (231278-84-5) → lapatanib (231277-92-2)

Conditions	Yield
Stage #1: 2-(methylsulfonyl)ethylamine hydrochloride With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 0.333333h; Stage #2: 5-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl)furan-2-carbaldehyde With acetic acid In tetrahydrofuran at 40℃; for 2h; Stage #3: With sodium tris(acetoxy)borohydride In tetrahydrofuran at 25 - 40℃; for 3h; Concentration;	100%
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 isopropyl alcohol at 50 - 60℃; for 4h; Stage #2: With sodium cyanoborohydride In isopropyl alcohol at 20℃; for 2h;	92.6%
Stage #1: 2-(methylsulfonyl)ethylamine hydrochloride With sodium sulfate; triethylamine In methanol at 0℃; for 0.333333h; Stage #2: 5-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl)furan-2-carbaldehyde With formic acid; sodium cyanoborohydride In tetrahydrofuran; methanol; N,N-dimethyl-formamide for 2h; pH=5 - 6;	82%

5-(4-(3-chloro-4-hydroxyphenylamino)quinazolin-6-yl)furan-2-carbaldehyde tosylate (1440511-82-9) + 2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4) → 2-chloro-4-(6-(5-((2-(methylsulfonyl)ethylimino)methyl)furan-2-yl)quinazolin-4-ylamino)phenol (1440511-83-0)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In methanol at 20 - 25℃; for 20h;	97.1%

C27H19ClFN3O3 + 2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4) → lapatanib (231277-92-2)

Conditions	Yield
With triethylamine In dichloromethane at 25 - 30℃; Inert atmosphere;	97%

2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4) + 5-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl)furan-2-carbaldehyde (231278-84-5) → N-(3-chloro-4-(3-fluorobenzyloxy)phenyl)-6-(5-((2-(methylsulfonyl)ethylimino)methyl)furan-2-yl)quinazolin-4-amine (1227853-06-6)

Conditions	Yield
With triethylamine In methanol for 12h; Reflux;	96%
With triethylamine In methanol for 12h; Reflux;	96%
With triethylamine In methanol for 12h; Reflux;

2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4) + toluene-4-sulfonic acid (104-15-4) + 5-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl)furan-2-carbaldehyde (231278-84-5) → lapatinib ditosylate (388082-78-8)

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

5-bromo-2-furancarboxaldehyde (1899-24-7) + 2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4) → (E)-N-((5-bromofuran-2-yl)methylene)-2-(methylsulfonyl)ethylamine

Conditions	Yield
Stage #1: 5-bromo-2-furancarboxaldehyde; 2-(methylsulfonyl)ethylamine hydrochloride With magnesium sulfate In dichloromethane at -5℃; for 2h; Inert atmosphere; Stage #2: With triethylamine In dichloromethane at -5℃; for 2h; Inert atmosphere;	94.25%

3-(3-(4-chloro-5-fluoropyrimidin-2-yl)-1-(2-fluorobenzyl)-1H-pyrazol-5-yl)isoxazole (1446358-48-0) + 2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4) → C20H18F2N6O3S

Conditions	Yield
With triethylamine In 1,4-dioxane; water at 100℃; for 17h;	91%

formaldehyd (50-00-0) + 6-(furan-2-yl)-4-[3-chloro-4-(3-fluorobenzyloxy)phenyl]aminoquinazoline + 2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4) → lapatanib (231277-92-2)

Conditions	Yield
In tetrahydrofuran at 35 - 40℃; for 4h;	90.3%

2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4) + D-arabinono-1,4-lactone 5-(dihydrogenophosphate) (219946-62-0) → N-(5-phosphate-D-arabinoyl)-2-(methylsulfonyl)ethanamine

Conditions	Yield
Stage #1: 2-(methylsulfonyl)ethylamine hydrochloride With sodium methylate at 35℃; Inert atmosphere; Stage #2: D-arabinono-1,4-lactone 5-(dihydrogenophosphate) With methanol at 20℃; for 1.5h; Inert atmosphere;	89%

ethyl 4-chloro-3-nitrobenzoate (16588-16-2) + 2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4) → ethyl 4-((2-(methylsulfonyl)ethyl)amino)-3-nitrobenzoate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 60℃; for 16h;	89%

2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4) + (±)-gossypol acetic acid (5453-04-3, 866541-93-7, 1189561-66-7) → C36H44N2O10S2

Conditions	Yield
Stage #1: 2-(methylsulfonyl)ethylamine hydrochloride With sodium hydroxide In ethanol for 1h; Reflux; Stage #2: (±)-gossypol acetic acid In ethanol for 5h; Reflux;	86.8%

4-((E)-{[1-(3-methylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]hydrazono}methyl)benzoic acid (650626-22-5) + 2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4) → 4-((E)-{[1-(3-methylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]hydrazono}methyl)-N-[2-(methylsulfonyl)ethyl]benzamide

Conditions	Yield
With diethyl cyanophosphonate; triethylamine In DMF (N,N-dimethyl-formamide) at 20℃; for 16h;	84%

2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4) + toluene-4-sulfonic acid (104-15-4) + 5-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl)furan-2-carbaldehyde (231278-84-5) → 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	Yield
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 With water In tetrahydrofuran at 20℃; for 12h;	82.8%

2-amino-5-[(5-formyl)furan-2-yl]benzonitrile p-toluenesulfonic acid + 2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4) → 2-amino-5-[5-[[[2-(methanesulfonyl)ethyl]amino]methyl]furan-2-yl]benzonitrile

Conditions	Yield
Stage #1: 2-amino-5-[(5-formyl)furan-2-yl]benzonitrile p-toluenesulfonic acid; 2-(methylsulfonyl)ethylamine hydrochloride With acetic acid; triethylamine In tetrahydrofuran at 20 - 35℃; for 1h; Stage #2: With sodium tris(acetoxy)borohydride In tetrahydrofuran at 22 - 25℃; for 2.5h;	82.7%

4-(4-(E)-(propen-1-yl)phenylamino)-6-(5-formylfuran-2-yl)quinazoline + 2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4) → 4-(4-(E)-(propen-1-yl)phenylamino)-6-(5-((2-(methylsulfonyl)ethyl)aminomethyl)furan-2-yl)quinazoline

Conditions	Yield
Stage #1: 2-(methylsulfonyl)ethylamine hydrochloride With sodium sulfate; triethylamine In methanol at 0℃; for 0.333333h; Stage #2: 4-(4-(E)-(propen-1-yl)phenylamino)-6-(5-formylfuran-2-yl)quinazoline With formic acid; sodium cyanoborohydride In tetrahydrofuran; methanol; N,N-dimethyl-formamide for 2h; pH=5 - 6;	82.6%

4-((E)-{[1-(6-methoxypyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]hydrazono}methyl)benzoic acid (650637-47-1) + 2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4) → 4-((E)-{[1-(6-methoxypyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]hydrazono}methyl)-N-[2-(methylsulfonyl)ethyl]benzamide

Conditions	Yield
With diethyl cyanophosphonate; triethylamine In DMF (N,N-dimethyl-formamide) at 20℃; for 16h;	81%

4-((E)-{[1-(2-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]hydrazono}methyl)benzoic acid + 2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4) → 4-((E)-{[1-(2-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]hydrazono}methyl)-N-[2-(methylsulfonyl)ethyl]benzamide hydrochloride

Conditions	Yield
Stage #1: 4-((E)-{[1-(2-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]hydrazono}methyl)benzoic acid; 2-(methylsulfonyl)ethylamine hydrochloride With diethyl cyanophosphonate; triethylamine In DMF (N,N-dimethyl-formamide) at 20℃; for 16h; Stage #2: With hydrogenchloride In water	81%

2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4) + 4-((E)-{[1-(3-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]hydrazono}methyl)benzoic acid (650627-05-7) → 4-((E)-{[1-(3-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]hydrazono}methyl)-N-[2-(methylsulfonyl)ethyl]benzamide

Conditions	Yield
With diethyl cyanophosphonate; triethylamine In DMF (N,N-dimethyl-formamide) at 20℃; for 16h;	81%

4-((E)-{[1-(3-nitrophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]hydrazono}methyl)benzoic acid (650626-44-1) + 2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4) → N-[2-(methylsulfonyl)ethyl]-4-((E)-{[1-(3-nitrophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]hydrazono}methyl)benzamide

Conditions	Yield
With diethyl cyanophosphonate; triethylamine In DMF (N,N-dimethyl-formamide) at 20℃; for 16h;	80%

2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4) + toluene-4-sulfonic acid (104-15-4) → 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

Yield

Stage #1: 5-(4-[3-chloro-4-(3-fluorobenzyloxy)-anilino]-6-quinazolinyl)-furan-2-carbaldehyde 4-methylbenzenesulfonate; 2-(methylsulfonyl)ethylamine hydrochloride With acetic acid; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 30 - 35℃; for 1h; Stage #2: With sodium tris(acetoxy)borohydride In tetrahydrofuran at 22℃; for 2h; Stage #3: toluene-4-sulfonic acid With sodium hydroxide; water more than 3 stages;

80%

5-[4-(tetrahydro-2H-pyran-2-yloxy)quinazolin-6-yl]furan-2-carbaldehyde (1383531-70-1) + 2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4) → 2-(methylsulphonyl)-N-({5-[4-(tetrahydro-2H-pyran-2-yloxy)quinazolin-6-yl]furan-2-yl}methyl)ethanamine (1383531-71-2)

Conditions	Yield
Stage #1: 5-[4-(tetrahydro-2H-pyran-2-yloxy)quinazolin-6-yl]furan-2-carbaldheyde; 2-(methylsulfonyl)ethylamine hydrochloride With N-ethyl-N,N-diisopropylamine In dichloromethane at 20 - 35℃; for 0.5h; Inert atmosphere; Stage #2: With sodium tris(acetoxy)borohydride In dichloromethane at 20 - 25℃; for 2h; Stage #3: With sodium hydrogencarbonate In dichloromethane	80%
Stage #1: 5-[4-(tetrahydro-2H-pyran-2-yloxy)quinazolin-6-yl]furan-2-carbaldheyde; 2-(methylsulfonyl)ethylamine hydrochloride With N-ethyl-N,N-diisopropylamine In dichloromethane at 30 - 35℃; for 0.5h; Inert atmosphere; Stage #2: With sodium tris(acetoxy)borohydride In dichloromethane at 20 - 25℃; for 2h;	80%
Stage #1: 5-[4-(tetrahydro-2H-pyran-2-yloxy)quinazolin-6-yl]furan-2-carbaldheyde; 2-(methylsulfonyl)ethylamine hydrochloride With N-ethyl-N,N-diisopropylamine In dichloromethane at 20 - 35℃; for 0.5h; Inert atmosphere; Stage #2: With sodium tris(acetoxy)borohydride In dichloromethane at 20 - 25℃; for 2h; Inert atmosphere;	80%

4-(3-ethynyl-phenylamino)-6-(5-formylfuran-2-yl)quinazoline + 2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4) → 4-(3-ethynylphenylamino)-6-(5-((2-(methylsulfonyl)ethyl)aminomethyl)furan-2-yl)quinazoline

Conditions	Yield
Stage #1: 2-(methylsulfonyl)ethylamine hydrochloride With sodium sulfate; triethylamine In methanol at 0℃; for 0.333333h; Stage #2: 4-(3-ethynyl-phenylamino)-6-(5-formylfuran-2-yl)quinazoline With formic acid; sodium cyanoborohydride In tetrahydrofuran; methanol; N,N-dimethyl-formamide for 2h; pH=5 - 6;	79.7%

4-(3-chloro-4-fluorophenylamino)-6-(5-formylfuran-2-yl)quinazoline (1421356-86-6) + 2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4) → 4-(3-chloro-4-fluorophenylamino)-6-(5-((2-(methylsulfonyl)ethyl)aminomethyl)furan-2-yl)quinazoline

Conditions	Yield
Stage #1: 2-(methylsulfonyl)ethylamine hydrochloride With sodium sulfate; triethylamine In methanol at 0℃; for 0.333333h; Stage #2: N-(3-chloro-4-fluorophenyl)-6-(5-formyl-2-furyl)-4-quinazolinamine With formic acid; sodium cyanoborohydride In tetrahydrofuran; methanol; N,N-dimethyl-formamide for 2h; pH=5 - 6;	78.1%

2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4) + trifluoroacetic acid (76-05-1) → (2-methanesulfonyl-ethyl)-(6-methyl-5-nitro-pyridin-2-yl)-amine trifluoroacetate (897732-57-9)

Conditions	Yield
Stage #1: 6-fluoro-2-methyl-3-nitro-pyridine; 2-(methylsulfonyl)ethylamine hydrochloride With potassium carbonate In tetrahydrofuran at 20 - 60℃; for 100h; Stage #2: trifluoroacetic acid	78%

(S)-4-(4-((2-hydroxy-1-phenylethyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-3-methoxybenzaldehyde (1637438-04-0) + 2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4) → (S)-2-((6-(2-methoxy-4-(((2-(methylsulfonyl)ethyl)amino)methyl)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)-2-phenylethan-1-ol

Conditions	Yield
Stage #1: 2-(methylsulfonyl)ethylamine hydrochloride With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.5h; Stage #2: (S)-4-(4-((2-hydroxy-1-phenylethyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-3-methoxybenzaldehyde In dichloromethane at 20℃; for 6h; Stage #3: With sodium tetrahydroborate In methanol for 3h;	77%

4-((E)-{[1-(4-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]hydrazono}methyl)benzoic acid (650626-61-2) + 2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4) → 4-((E)-{[1-(4-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]hydrazono}methyl)-N-[2-(methylsulfonyl)ethyl]benzamide

Conditions	Yield
With diethyl cyanophosphonate; triethylamine In DMF (N,N-dimethyl-formamide) at 20℃; for 16h;	76%

Upstream product

• 18542-42-2 (2-aminoethyl)methylsulfide 
• 49773-20-8 2-Methanesulfonyl-ethylamine 
• 154095-06-4 tert-butyl 2-(methylsulfonyl)ethylcarbamate 

Downstream Products

• 1227853-06-6 N-(3-chloro-4-(3-fluorobenzyloxy)phenyl)-6-(5-((2-(methylsulfonyl)ethylimino)methyl)furan-2-yl)quinazolin-4-amine 
• 49773-20-8 2-Methanesulfonyl-ethylamine 
• 231277-92-2 lapatanib 
• 700818-78-6 4-{1-ethyl-1-[4-(2-hydroxy-3,3-dimethylbutoxy)-3-methylphenyl] propyl}-N-(2-methanesulfonylethyl)-2-methylbenzamide 

Relevant articles and documents

Preparation method of Lapatinib side chain 2-(methyl sulfonyl) ethylamine salt

The invention provides a preparation method of Lapatinib side chain 2-(methylsulfonyl) ethylamine salt. The method comprises the following steps: (A) performing reaction on one or two of 2-bromoethylamine and 2-bromoethylamine salt and di-tert-butyl dicarbonate methyl ester under the alkaline condition to obtain N-(Boc)-2-bromoethylamine; (B) performing reaction on the N-(Boc)-2-bromoethylamine and sodium methanesulfinate under the alkaline condition to obtain N-(Boc)-2- methylsulfonyl ethylamine; (C) acidifying the N-(Boc)-2-methylsulfonyl ethaneamine to obtain the Lapatinib side chain 2-(methylsulfonyl) ethylamine salt. The preparation method of the Lapatinib side chain 2-(methylsulfonyl) ethylamine salt, provided by the embodiment of the invention, avoids the occurrence of the problems that when an oxidization method is used for synthesizing a target product, unstable factors are many, and the operation of the obtained product is also unsafe. The preparation method has the advantages that the operation steps are simple and convenient; the molecule utilization degree is high; the reaction conditions can be easily controlled; the operation cost is low; the post treatment operation is simple and convenient; the purity of the obtained product is high.

Lapatinib process for the preparation of intermediates

The invention discloses a preparation method of a Tykerb intermediate. The preparation method of the Tykerb intermediate 1 comprises the following steps: (1) performing a nucleophilic substitute reaction on a compound as shown in a formula 3 and a compound as shown in a formula 4 under the effect of a catalyst in an organic solvent, wherein X is chlorine or bromine, M is sodium, potassium or zinc, and n is equal to 1 or 2; and (2) enabling a compound 2 obtained in the step (1) to react in a hydrogen chloride solution. According to the preparation method of the Tykerb intermediate 2, the nucleophilic substitute reaction is carried out on the compound as shown in the formula 3 and the compound as shown in the formula 4 under the effect of the catalyst in the organic solvent. The preparation method disclosed by the invention is simple to operate, the raw materials are cheap and easy to obtain, no environment pollution factor is caused, and the method is suitable for large-scale production in industry.

THE NEW PREPARATION OF ALIPHATIC AMINES WITH SULPHONYL GROUP AND THEIR SALTS

The present invention relates to a novel preparation method of sulfonyl alkylamine and salts thereof. The method of present invention comprises steps of: adopting sulfonates containing a sulfone moiety as starring material and ammonia oz amine as substituting agent which reacts with the starting material to prepare for the products. Furthermore, the present invention provides a new intermediate 2-(N,N- dibenzylamino) ethyl methyl sulfone and salts thereof obtained from the above novel preparation method and their use. In addition, the present invention also provides a novel salt of 2-(anuno) ethyl methyl sulfone prepared using 2-(amine) ethyl methyl sulfone hydrochloride and the use of novel salt. The present invention is not only advantageous for reducing environmental pollution, but also could be used for mass fabrication of 2-(amino) ethyl methyl sulfone and the salts thereof, in addition, the present invention is advantageous for preparing for the highly purified 2-(amine) ethyl methyl sulfone hydrochloride.