ChemicalBook CAS DataBase List Lapatinib ditosylate

Lapatinib ditosylate synthesis

8synthesis methods

Product Name:Lapatinib ditosylate
CAS Number:388082-78-8
Molecular formula:C41H40ClFN4O11S3
Molecular Weight:925.46

49773-20-8
58 suppliers
$41.00/250mg

104-15-4
734 suppliers
$133.00/500g

231278-84-5 Synthesis

5-[4-((3-Chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)quinazolin-6-yl]-2-furaldehyde

231278-84-5
286 suppliers
$8.00/250mg

388082-78-8
342 suppliers
$6.00/50mg

Yield:388082-78-8 93%

Reaction Conditions:

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;

Steps:

7

Example 7:Preparation of A/-(3-chloro-4-{[(3-fluorophenyl)methyl]oxy}phenyl)-6-[5-({[2- (methylsulfonyl)ethyl]amino}methyl)-2-furanyl]-4-quinazolinamine bis 4- methylbenzenesulfonate.The suspension of 5-[4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)quinazolin-6-yl]-2-furaldehyde (5 g, 10.6 mmoL) in dichloromethane (50ml_) was charged with a solution of 2-aminoethylmethylsulfone (3.2 g, 1 1.7mmoL) in methanol (25ml_) slowly under constant stirring at room temperature. The reaction mixture was stirred for 2-4 hours until reaction completion. The reaction mixture was charged with 5% Pd-C (750mg) and stirred under hydrogen atmosphere using balloon pressure for 12-16 hours until reaction completion. The obtained mixture was filtered through Celite pad and rinsed with methanol (5 mL) and dichloromethane (15 mL) mixture. The filtrate was distilled to low volume and the solution was charged with dichloromethane (25 mL) followed by addition of the solution of p-toluenesulfonic acid monohydrate (4.4 g, 23.3 mmoL) in methanol (10 mL). The yellow solid which precipitated out was filtered after 2- 8 hours and washed with 1 :1 mixture of methanol and dichloromethane (20 mL). The solid obtained was dried under vacuum at 40-45°C to provide Lapatinib (1 1.4 g, Yield = 93%, HPLC purity >99%).

References:

WO2012/83440,2012,A1 Location in patent:Page/Page column 13-14