145783-15-9 Usage
Description
4,6-dichloro-2-propylthiopyrimidine-5-amine is an organic compound with the molecular formula C8H10Cl2N4S. It is a light pink to dark brown liquid or semi-solid, which serves as an intermediate in the synthesis of Ticagrelor (T437700) and other reversible P2Y12 receptor antagonists. These receptor antagonists are significant in the pharmaceutical industry due to their potential therapeutic applications.
Uses
Used in Pharmaceutical Industry:
4,6-dichloro-2-propylthiopyrimidine-5-amine is used as a key intermediate in the synthesis of Ticagrelor, a drug that inhibits platelet aggregation by reversibly blocking the P2Y12 receptor. 4,6-dichloro-2-propylthiopyrimidine-5-amine plays a crucial role in the development of antiplatelet agents for the treatment of cardiovascular diseases, such as acute coronary syndrome and stroke.
Additionally, 4,6-dichloro-2-propylthiopyrimidine-5-amine is utilized in the preparation of other reversible P2Y12 receptor antagonists, which have potential applications in the treatment of various thrombotic disorders and conditions related to blood clotting.
Synthesis
The synthesis of 4,6-dichloro-2-propylthiopyrimidine-5-amine is as follows：tert-Butyl methyl ether (370 g) was placed under nitrogen in a 1 L stainless steel autoclave equipped with a temperature-controlled jacket, an Ekato InterMIG stirrer, an internal temperature sensor and a dip pipe, and 4,6-dichloro-5-nitro-2-propylsulfanyl-pyrimidine (94.5 g, 0.35 mol) was added and dissolved at a stirring rate of 200 min-1. The catalyst suspension was prepared and transferred into the autoclave as described in the preceding example. The autoclave was sealed and the stirring rate was increased to 600 min-1 while the autoclave was purged four times with nitrogen. Subsequently, hydrogen gas feed via the dip pipe at a constant flow rate (pmax=10 bar) as well as a heating-up ramp (45 K/h) from 20° C. to 65° C. were started in parallel, while stirring at 600 min-1. The progress of the exothermic reaction was followed by recording the hydrogen uptake as well as the internal and jacket temperature curve. Upon completion of the hydrogen uptake (ca. 1.1 mol or 3 molar equivalents) after about 4 h, stirring of the reaction mixture was continued for an additional 3 hours at 65° C. After unloading the autoclave (the reactor was cooled down to 20° C., the hydrogen pressure was released and the reactor purged four times with nitrogen), the catalyst was filtered off. The autoclave as well as the filter cake (catalyst) were washed with tent-butyl methyl ether (185 g). The organic phases were combined and the water layer separated. An IPC-sample was taken to analyze the product mixture. The conversion was found to be quantitative with no nitroso or hydroxylamine intermediate being detectable.
Check Digit Verification of cas no
The CAS Registry Mumber 145783-15-9 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,4,5,7,8 and 3 respectively; the second part has 2 digits, 1 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 145783-15:
(8*1)+(7*4)+(6*5)+(5*7)+(4*8)+(3*3)+(2*1)+(1*5)=149
149 % 10 = 9
So 145783-15-9 is a valid CAS Registry Number.
InChI:InChI=1/C7H9Cl2N3S/c1-2-3-13-7-11-5(8)4(10)6(9)12-7/h2-3,10H2,1H3
145783-15-9Relevant articles and documents
Preparation method of ticagrelor intermediate
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Paragraph 0004; 0006-0009, (2021/07/09)
The invention provides a preparation method as shown in a formula I shown in the specification, especially, a preparation method of 4, 6-dichloro-2-(propylthio)-5-aminopyrimidine. The invention provides a novel method for preparing the ticagrelor intermediate.
Purification method of 4,6-dichloro-2-(thiopropyl)-5-aminopyrimidine
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Paragraph 0060-0069, (2020/10/21)
The invention discloses a purification method of 4,6-dichloro-2-(thiopropyl)-5-aminopyrimidine. The method comprises steps including oil removal, salification, dissociation and recrystallization purification of a crude 4,6-dichloro-2-(thiopropyl)-5-aminopyrimidine product to finally obtain high-purity 4,6-dichloro-2-(thiopropyl)-5-aminopyrimidine. The purification method disclosed by the inventionis simple and convenient to operate, high in yield and suitable for large-scale production.
Synthesis method of ticagrelor intermediate
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Paragraph 0056-0058, (2020/06/16)
The invention provides a synthesis method of a ticagrelor intermediate 1. By selecting a more stable amino protecting group, the formation of by-products in the cyclization step is favorably controlled, the reaction conditions in each step are mild, the conversion rate is higher, the cost is effectively reduced, and the method is suitable for industrial production.
