435-97-2

Usage

Uses

Used in Pharmaceutical Industry:
Phenprocoumon is used as an oral anti-coagulant for the prevention and treatment of blood clots. It works by inhibiting the synthesis of vitamin K-dependent clotting factors, thereby reducing the risk of thromboembolic events such as deep vein thrombosis, pulmonary embolism, and stroke. Additionally, it is used in the management of atrial fibrillation and in patients with prosthetic heart valves.
Used in Cardiovascular Applications:
Phenprocoumon is used as a therapeutic agent in the treatment of cardiovascular conditions where there is an increased risk of blood clot formation. It helps in maintaining a balance between the clotting and bleeding processes, ensuring that the blood remains fluid and preventing the formation of harmful blood clots.
Used in Atrial Fibrillation Management:
Phenprocoumon is used as an anti-coagulant in the management of atrial fibrillation, a common heart rhythm disorder. By reducing the risk of blood clot formation, it helps in preventing stroke and other thromboembolic complications associated with this condition.
Used in Prosthetic Heart Valve Patients:
Phenprocoumon is used as an anti-coagulant in patients with prosthetic heart valves to prevent the formation of blood clots around the artificial valve, which can lead to valve dysfunction or embolic events.

Originator

Liquamar ,Organon ,US,1958

Manufacturing Process

8.3 parts by weight of powdered sodium in 300 parts by volume of benzene, 100 parts by weight of diethyl (1'-phenylpropyl)-malonate and 72 parts by weight of acetylsalicylic acid chloride are reacted together to form diethyl 1(o-acetoxybenzoy1)-1-(1'-phenylpropyl)malonate, which boils at 195°198°C/0.03 mm Hg.10.3 parts of weight of diethyl 1-(o-acetoxybenzoyl)-1-(1'-phenylpropyl)malonate are dissolved in 60 parts by volume of absolute ether and to this solution are added portion. wise at 10°C, while stirring, 2.6 parts by weight of sodium methylate. The reaction mixture is stirred for 4 hours, whereupon it is poured into ice water. The ether solution is washed neutral with ice water. After having distilled off the ether, a thick oil consisting of 3-carbethoxy-3-(1'phenylpropyl)-4-oxo-dihydrocoumarinis obtained. Phenprocoumon crystallized in butyl oxide and has a MP of 108°-109°C.The 3-carbethoxy-3-(1'-phenylpropyl)-4-oxo-dihydrocoumarinmay be hydrolyzed and decarboxylated as follows. The crude product is heated to 85°C for 1/2 hour with 100 parts by volume of 5% aqueous sodium hydroxide, while agitating or stirring. To remove traces of undissolved oil, the cooled solution is treated with 1 part by weight of charcoal, whereupon it is filtrated and acidified to Congo reaction with dilute sulfuric acid. The 3-(1'phenylpropyl)-4-hydroxycoumarin formed is separated off and recrystallized in 80% ethanol, whereupon it melts at 178°-179°C according to US Patent 2,701,804.

Therapeutic Function

Anticoagulant

Synthesis

Phenprocoumon, 3-(α-ethylbenzyl)-4-hydroxycoumarin (24.1.14), is synthesized by acylating sodium salts of diethyl ester (1-phenylpropyl)butyric acid with acetylsalicylic acid chloride, which forms the compound 24.1.12, which upon reaction with sodium ethoxide cyclizes to 3-(α-ethylbenzyl)-2-carboethoxy-4-hydroxycoumarin (24.1.13). Alkaline hydrolysis of this product and further decarboxylation gives phenprocoumon(24.1.14).

InChI:InChI=1/C18H16O3/c1-2-13(12-8-4-3-5-9-12)16-17(19)14-10-6-7-11-15(14)21-18(16)20/h3-11,13,19H,2H2,1H3

Upstream product

• 1076-38-6 4-hydroxy[1]benzopyran-2-one 
• 93-54-9 1-Phenyl-1-propanol 
• 2941-20-0 1-phenylpropylamine 
• 637-50-3 1-phenylpropene 
• 25574-04-3 1-p-tolyl-1-propanol 
• 93-55-0 1-phenyl-propan-1-one 
• 2157-50-8 propiophenone oxime 

Downstream Products

• 3770-63-6 [13C]-(-)-Phenprocoumon 

Relevant academic research and scientific papers

An expedient solvent-free C-benzylation of 4-hydroxycoumarin with styrenes

An efficient straightforward solvent-free C(3)-benzylation of 4-hydroxycoumarin with styrenes is performed by heating the reactants in the presence of p-toluenesulfonic acid. By this procedure, benzylated 4-hydroxycoumarin derivatives which exhibit variou

HFIP Promoted C3 Alkylation of Lawsone and 4-Hydroxycoumarin with Alcohols by Dehydrative Cross-Coupling

An environmentally benign system for the direct alkylation of lawsones and 4-hydroxycoumarins with alcohols in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) is reported. The reaction proceeded smoothly via a dehydrative cross-coupling process by utilizing the unique properties of HFIP. A variety of alkylated products and subsequent one-pot cyclized products (pyranonaphthoquinones and pyranocoumarins) could be obtained in 40-93% yields.

Metal-Free C-O Bond Functionalization: Catalytic Intramolecular and Intermolecular Benzylation of Arenes

A catalytic, metal-free intramolecular rearrangement of benzyl phenyl ethers using nitrosonium salt as a catalyst is described. The optimized reaction conditions enabled a catalytic and metal-free Friedel-Crafts alkylation reaction with benzylic alcohols, producing water as the stoichiometric byproduct. A comprehensive scope (>50 examples) for both approaches and application in drug synthesis were demonstrated. Mechanistic studies suggest a Lewis acid-based mechanism for the metal-free Friedel-Crafts reaction.

Regioselective Access to Structurally Diverse Coumarin Analogues through Iron-Catalysed Annulation Reactions

A highly efficient iron-catalysed propargylation/alkyne oxacyclization/isomerization strategy is described. Biologically active furo[3,2-c]coumarins and pyrano[3,2-c]coumarins are expeditiously assembled in moderate to good yields and with a broad substrate scope. The regioselective access to different coumarins is mainly dependent on the terminal group of the secondary propargylic alcohol.

Synthesis method of propafenone drug intermediate 3-(alpha-ethylbenzyl)-4-hydroxyl coumarin

A synthesis method of a propafenone drug intermediate 3-(alpha-ethylbenzyl)-4-hydroxyl coumarin includes the following steps that 0.21 mol of 4-hydroxyl coumarin and 0.26-0.29 mol of alpha-ethyl benzyl amine are added into a reaction vessel, the solution temperature is raised to 110-115 DEG C, the reaction time is 3-5 hours, the solution temperature is reduced to 10-15 DEG C, 300 ml of a potassium sulfite solution is added, acetonitrile is used for extracting the excessive alpha-ethyl benzyl amine, the solution is poured into 1.3 L of an oxalic acid solution, solid precipitation, filtration and washing with a saline solution are performed, a filter cake is added into 2.3 L of a potassium bromide solution, the solution temperature is raised to 90-95 DEG C and is kept for 2-3 hours, the solution temperature is reduced to 5-9 DEG C, solid precipitation, washing with cyclohexane and dehydration with a dehydrating agent are performed, and recrystallization is performed in nitromethane to obtain the crystal 3-(alpha-ethylbenzyl)-4-hydroxyl coumarin.

Nitrimines as reagents for metal-free formal C(sp2)-C(sp2) cross-coupling reactions

Nitrimines are employed as powerful reagents for metal-free formal C(sp2)-C(sp2) cross-coupling reactions. The new chemical process is tolerant of a wide array of nitrimine and heterocyclic coupling partners giving rise to the corresponding di- or trisubstituted alkenes, typically in high yield and with high stereoselectivity. This method is ideal for the metal-free construction of heterocycle-containing drug targets, such as phenprocoumon.

Direct catalytic benzylation of hydroxycoumarin - Efficient synthesis of warfarin derivatives and analogues

Effective metal-catalyzed benzylations of 4-hydroxycoumarin have been developed. Employing a low amount of a cheap, nontoxic, and air-stable catalyst the 3-alkylated hydroxycoumarins were isolated in high yields after short reaction times. Applying this new methodology two widely used anticoagulants phenprocoumon and coumatetralyl were synthesized applying mild reaction conditions. Georg Thieme Verlag Stuttgart New York.

A general and efficient iron-catalyzed benzylation of 1,3-dicarbonyl compounds

Various CH-acidic 1,3-dicarbonyl compounds and methyl 3-acetamidobut-2- enoate react with benzylic alcohols to give the corresponding 2-benzylated products in good to excellent yield. Typically, reactions proceed under mild conditions (50-80°C; air) in the presence of catalytic amounts of inexpensive iron chloride hexahydrate. The benzylation of 4-hydroxycoumarin gives the pharmaceutically interesting 4-hydroxy-3-(1-phenylethyl)-2H-chromen-2- ones. As an example the anticoagulant Phenprocoumon is prepared in one step from commercially available substrates in 94 % yield.

4-HYDROXY-BENZOPYRAN-2-ONES AND 4-HYDROXY-CYCLOALKYL[B]PYRAN-2-ONES USEFUL TO TREAT RETROVIRAL INFECTIONS

The present invention relates to compounds of formula I which are 4-hydroxy-benzopyran-2-ones and 4-hydroxy-cycloalkyl[b]pyran-2-ones useful for inhibiting a retrovirus in a mammalian cell infected with said retrovirus. STR1 Wherein R 10 and R 20 taken together are: STR2