330942-05-7

Basic information

• Product Name: Betrixaban
• Synonyms: Betrixaban;N-(5-Chloropyridin-2-yl)-2-[[4-(N,N-dimethylcarbamimidoyl)benzoyl]amino]-5-methoxybenzamide;1-C-{4-[aMino(diMethylaMino)Methyl]benzene}-2-N-(5-chloropyridin-2-yl)-4-Methoxybenzene-1,2-dicarboxaMide;N-(5-Chloro-2-pyridinyl)-2-[[4-[(diMethylaMino)iMinoMethyl]benzoyl]aMino]-5-MethoxybenzaMide;PRT 054021;N-(5-chloropyridin-2-yl)-2-(4-(N,N-diMethylcarbaMiMidoyl)benzaMido)-4-MethoxybenzaMide;Betrixaban N-(5-Chloropyridin-2-yl)-2-[[4-(N,N-dimethylcarbamimidoyl)benzoyl]amino]-5-methoxybenzamide;N-(5-Chloropyridin-2-yl)-2-[[4-(N,N-dimethylcarbamimidoyl)benzoyl]amino]-5-methoxybenzamide Betrixaban
• CAS NO: 330942-05-7
• Molecular Formula: C₂₃H₂₂ClN₅O₃
• Molecular Weight: 451.90548
• EINECS: 682-459-2
• Product Categories: Aromatics;Heterocycles;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals;API
• Mol File: 330942-05-7.mol

Chemical Properties

• Appearance: /
• Density: 1.3g/cm³
• Refractive Index: 1.628
• Storage Temp.: 2-8°C
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 11.00±0.70(Predicted)
• CAS DataBase Reference: Betrixaban(CAS DataBase Reference)
• NIST Chemistry Reference: Betrixaban(330942-05-7)
• EPA Substance Registry System: Betrixaban(330942-05-7)

Safety Data

• Hazardous Substances Data: 330942-05-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Betrixaban is used as an anticoagulant for the prevention of venous thromboembolism (VTE) in patients. It serves as a direct inhibitor of factor Xa, which is a crucial component in the coagulation process. By inhibiting factor Xa, betrixaban effectively reduces the risk of blood clot formation, making it a valuable asset in the prevention and management of VTE.

Biological Activity

betrixaban is a highly potent, selective, and orally efficacious inhibitor of factor xa with ic50 value of 1.5nm [1].betrixaban shows excellent anticoagulant potency in vitro. in the rabbit deep vein thrombosis model, the concentration of betrixaban required to double the rabbit prothrombin time is below 2μm. betrixaban is selective for fxa and has poor activity for thrombin, trypsin, t-pa and apc. the patch clamp herg assay shows that betrixaban has low affinity with herg suggesting it is safer than other candidate compounds. in addition, betrixaban displays a profile of good oral bioavailability and oral exposure, long half-life in animal models. it has bioavailability of 51.6% at dose of 0.5 mg/kg iv and 2.5 mg/kg po. furthermore, the phase ii study has proved betrixaban as an oral fxa inhibitor for prevention of venous thromboembolic events [1].

references

[1] zhang p, huang w, wang l, bao l, jia zj, bauer sm, goldman ea, probst gd, song y, su t, fan j, wu y, li w, woolfrey j, sinha u, wong pw, edwards st, arfsten ae, clizbe la, kanter j, pandey a, park g, hutchaleelaha a, lambing jl, hollenbach sj, scarborough rm, zhu by. discovery of betrixaban (prt054021), n-(5-chloropyridin-2-yl)-2-(4-(n,n-dimethylcarbamimidoyl)benzamido)-5-methoxybenzamide, a highly potent, selective, and orally efficacious factor xa inhibitor. bioorg med chem lett. 2009 apr 15;19(8):2179-85.

InChI:InChI=1/C23H22ClN5O3/c1-29(2)21(25)14-4-6-15(7-5-14)22(30)27-19-10-9-17(32-3)12-18(19)23(31)28-20-11-8-16(24)13-26-20/h4-13,25H,1-3H3,(H,27,30)(H,26,28,31)

Upstream product

• 330942-01-3 N-(5-chloro(2-pyridyl)){2-[(4-cyanophenyl)carbonylamino]-5-methoxyphenyl}carboxamide 
• 3585-33-9 lithium dimethylamide 
• 40465-45-0 p-cyanophenyl isocyanate 
• 64459-25-2 4-cyanophenyl chloroformate 
• 124-40-3 dimethyl amine 
• 88905-74-2 dimethylaminomagnesium chloride 
• 7377-26-6 4-Methoxycarbonylbenzoyl chloride 
• 1679-64-7 Monomethyl terephthalate 
• 34231-49-7 4-(N,N-Dimethylaminocarbonyl)benzoic acid 
• 21928-11-0 methyl 4-(dimethylcarbamoyl)benzoate 
• 280773-17-3 2-amino-N-(5-chloro-pyridin-2-yl)-5-methoxy-benzamide 
• 37795-77-0 6-methoxy-2H-3,1-benzoxazine-2,4(1H)-dione 

Downstream Products

• 936539-80-9 N-(5-chloropyridin-2-yl)-2-[4-(N,N-dimethylcarbamimidoyl)benzamido]-5-methoxybenzamide maleic acid salt 
• 1616693-46-9 5-(2-((6-amidohexyl)amino)-2-oxoethyoxy)-N-(5-chloropyridin-2-yl)-2-(4-(N,N-dimethylcarbamimidoyl)benzamido)benzamide 
• 1616693-61-8 C₂₂H₂₁N₅O₃ 
• 1616693-60-7 C₂₃H₂₃N₅O₃ 
• 1514962-30-1 5-(2-((6-amidohexyl)amino)-2-oxoethyoxy)-2-(4-(N,N-dimethylcarbamimidoyl)benzamido)-N-(pyridine-2-yl)benzamide 
• 1616693-59-4 C₂₂H₂₀ClN₅O₃ 

Relevant articles and documents

Preparation method of beta-caraban

The preparation method comprises the following steps: in liquid dimethylamine, a compound of the structural formula II or a salt thereof and MN (CH). 3 )2 The dimethylamine solution in the structural formula I is reacted to obtain the fritilth. M represents Li or MgX; and M is Li or Na. Wherein X is selected from one of Cl, Br and I. The preparation method disclosed by the invention is high in yield and high in product purity, can substantially avoid generation of single methyl ammonia impurities and dechlorination impurities, and greatly simplifies the subsequent refining process. In addition, the preparation method is single in solvent, the use of the mixed solvent is avoided, the later-stage solvent recovery is convenient, and the three wastes can be reduced.

Improved preparation method of beta-caraban

The invention relates to the fields of organic chemistry and pharmacy, and particularly relates to an improved method for preparing betrixaban. Compared with the prior art, the method has the advantages that the defects of use of high-corrosion hydrogen chloride gas, heavy burden for 'three wastes' treatment, difficult refining and purification of products and the like can be overcome. The method is characterized in that a metal organic compound RMR' (M is selected from Mg and Zn, R is selected from Cl, Br, I, alkyl or aryl, and R' is selected from akly or aryl) is used for reacting with dimethylamine or salt thereof in an aprotic solvent; then the obtained reacting liquid reacts with the compound or salt thereof in a formula II to prepare betrixaban. The improved novel method has the advantages of use of easily available raw materials, mild reaction condition, convenience in operation, excellent product quality and low cost and is suitable for industrial large-scale production.

Novel betrixaban intermediate and preparation method and application thereof

The invention discloses a novel betrixaban intermediate and a preparation method and application thereof. The structure of the intermediate is shown in formula I. The intermediate can achieve efficient and high-yield construction of an N,N-dimethylcarbamimidoyl structure fragment in the betrixaban structure through a bio-enzyme catalysis method, and has the advantages of being green and environmentally friendly.

Synthetic process of betrixaban

The invention provides a synthetic process of betrixaban, and particularly relates to the field of pharmaceutical manufacturing. S1, 1-(3-dimethyl amine propyl)-3-ethyl carbon imidodicarbonic diamide,N-hydroxysuccinimide (NHS) and paracyanobenzoic acid are introduced into a solution, and activation of cyanobenzoic acid is achieved; S2, the activated cyanobenzoic acid reacts with 2-amine-N-(5-chlorine group-2-pyridyl)-5-methoxybenzamide, appropriate methyl alcohol is added in a reaction container, cooling is conducted for devitrification, and a midbody I is obtained through filter; S3, moistureless condition is guaranteed, and acetylchloride is dropwise added; the midbody I is added, and evaporation is conducted until it is guaranteed that materials are dried; reaction with a tetrahydrofuran solution of dimethylamine is conducted, and a midbody II is generated under action of sodium hydroxide; and S4, the midbody II reacts with maleic acid at 60-70 DEG C to obtain the betrixaban. According to the synthetic process of the betrixaban, the reaction condition is mild, the yield is high, impurities are less, gas preparation is reduced, corrosion on equipment is reduced, and the cost oflater-stage environmental protective treatment is low.

Preparation method of betrixaban intermediate and betrixaban and product thereof

The invention relates to a preparation method of a betrixaban intermediate or salt thereof. The method includes: under the action of a catalyst, adding an amide coupling reagent dropwise into a compound shown as formula SM-III and a compound shown as formula SM-I or salts thereof for condensation reaction in an organic solvent to form a compound shown as formula III or a salt thereof, and furtherpreparing the betrixaban intermediate or the salt thereof into betrixaban or a salt thereof. The betrixaban or the hydrochloride thereof prepared by the method provided by the invention basically doesnot contain dechlorinated impurity V or demethylated impurity VI, and has high purity. The method improves the product yield, reduces the use of high corrosive raw materials, is low in cost, and is suitable for industrial production.

SALTS OF BETRIXABAN AND PROCESSES FOR PREPARATION THEREOF

The present application relates to novel acid addition salts of Betrixaban and processes for their preparation thereof. It further relates to crystalline forms including its solvates and hydrates of Betrixaban novel acid addition salts. The application further concerns pharmaceutical compositions comprising the novel acid addition salts of the Betrixaban, useful as potent fXa inhibitors.

Preparation method of betrixaban maleate

The invention provides a preparation method of betrixaban maleate. According to the preparation method, paracyanobenzoic acid and 2-amino-N-(5-chloro-2-pyridyl)-5-methoxy benzamide are subjected to acoupled reaction; in a coupling process, a new coupling catalyst is selected for use; EDC and NHS are applied to a combined way; a coupling product reacts with alcohol under the acidic condition so asto generate pinner salt; in the process, acetyl chloride is enabled to react with alcohols, so that hydrogen chloride needed by the reaction is provided. The way of directly introducing hydrogen chloride gas is eliminated, so that gas preparation and corrosion of equipment are reduced. In a whole reaction process, the method is mild in reaction conditions and higher in yield, thus being suitablefor industrial production.

Bei quxi class crystal form and its preparation and use

The invention discloses crystal forms of a factor Xa inhibitor betrixaban, a preparing method thereof, pharmaceutical compositions comprising the crystal forms of the betrixaban, and uses of the crystal forms of the betrixaban in preparation of medicines used for preventing or treating mammal diseases characterized by adverse thrombus formation.

Midbody for betrixaban, preparation method and application of midbody

The invention discloses a midbody for betrixaban, a preparation method and application of the midbody. The structure of the midbody is as shown in formula I described in specification. The midbody can be effectively compounded by using the low-cost easily acquired raw materials, and meanwhile, the subsequent reaction yield is high and the post-processing is simple when the raw materials are used for compounding the betrixaban, and the acquired product is high in purity and has wide industrial application prospect.

Preparation method of Betrixaban or analogue thereof

The invention discloses a preparation method of Betrixaban or an analogue thereof. The preparation method of the Betrixaban comprises the steps of adopting N-(5-chloropyridine-2-radical)-5-methoxyl-2-aminobenzamide (A) as a raw material, carrying out amide condensation reaction on the raw material and cyanobenzoyl chloride (B), treating through an alkali liquor, and obtaining a formula D compound. Amino magnesium chloride and the formula D compound or salt thereof are adopted to prepare a Betrixaban free alkali compound (I) or the analogue thereof.