898543-06-1Relevant articles and documents
Preparation of intermediates (by machine translation)
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Paragraph 0004; 0035-0037, (2020/10/19)
In the method of manufacturing a method of manufacturing problems [to] [ribarokisaban[ribarokisaban][ribarokisaban[ribarokisaban] which, in particular, intermediate compounds on an industrial scale manufacturing method is excellent in operability. [Solution] water-miscible organic solvent other than alcohols in, 2 - ({(5S) -2 - [4 - (3 - oxo--4 - morpholinyl) - phenyl] - 1, 3 - oxazolidine -3 - oxo -5 - yl} methyl) - 1, 3 (2H) dione is reacted with methylamine - 1H - isoindole, 2 layers separated from the solution 4 - {4 - [(aminomethyl) - 1, 3 - oxazolidine -3 - oxo (5S) -5 - -2 - yl] - phenyl} morpholine hydrochloride is precipitated on the production of -3 -, and method of manufacturing the compound [ribarokisaban[ribarokisaban]. Figure 4 [drawing] (by machine translation)
Preparation and application of key intermediate of rivaroxaban
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Paragraph 0034; 0037-0042, (2019/09/14)
The invention provides preparation and application of a key intermediate of rivaroxaban. Experiment conditions of a Gabriel method are optimized, and results show that a specific solvent is a key parameter which affects the purity and the yield of a rivaroxaban intermediate. The rivaroxaban prepared by the invention is high in yield and good in purity, and is capable of meeting quality standards of raw material medicines without recrystallization.
Preparation method of rivaroxaban intermediate
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, (2019/12/25)
The invention discloses a preparation method of a Rivaroxaban intermediate. The preparation method includes the following steps that (1) in existence of an organic lithium salt or the organic lithiumsalt and an inorganic lithium salt, a compound in a following formula I is reacted with a compound in a following formula II to obtain a compound in a following formula III; and (2) the compound in the formula III is subjected to an acidification reaction in existence of inorganic acid HX, the Rivaroxaban intermediate shown in a following formula IV is obtained, wherein R in the compound in the formula I is selected from methyl, isopropyl, normal-butyl and phenyl or benzyl, and the inorganic acid HX is selected from hydrochloric acid or sulfuric acid. The preparation method is easy to operateand high in yield, and industrial production and patent medicine quality control are convenient.
Preparation method and use of rivaroxaban intermediate
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Paragraph 0028; 0030, (2019/04/26)
The present invention relates to a preparation method of a rivaroxaban intermediate I. The method provided by the invention has the advantages of greatly shortening the reaction time, easy preparationby scale, simple operation, good stability, high purity, low environmental pollution and suitable for industrial production.
(S)- {1 - (chloromethane ester) - 2 - [2 - (1, 3 - two oxygen different indole) yl] ethyl} halide salt and its preparation method
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Paragraph 0102-0104, (2017/08/25)
The present invention discloses a compound (S)-{1-(chloroformate)-2-[2-(1,3-dioxo-isoindol)yl]ethyl}halogenation salt represented by a formula VI, and a preparation method thereof, wherein X represents a halogen. According to the present invention, the compound is used for preparing the rivaroxaban key intermediate (S)-2-{[2-oxo-3-(4-(3-oxomorpholino)phenyl)oxazolidine-5-yl]methyl}isoindole-1,3-dione and/or rivaroxaban intermediate, and the obtained product is firstly obtained through the method in the present invention; and the preparation method is mature and reliable, and can be suitable for industrial large-scale production. The formula VI is defined in the specification.
4 - (4 - a ammonia alkenyl phenyl) - 3 - morpholone and its preparation method
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Paragraph 0093; 0094; 0095; 0096; 0097; 0098; 0099, (2017/08/25)
The present invention discloses a compound 4-(4-methylamino alkenyl phenyl)-3-morpholinone represented by a formula III, and a preparation method thereof. According to the present invention, the compound is used for preparing the rivaroxaban key intermediate (S)-2-{[2-oxo-3-(4-(3-oxomorpholino)phenyl)oxazolidine-5-yl]methyl}isoindole-1,3-dione and/or rivaroxaban intermediate, and the obtained product is firstly obtained through the method in the present invention; and the operation of the preparation method is simple, the yield is up to about 90%, and the product purity is good. The formula III is defined in the specification.
NOVEL MORPHOLINE DIPHOSPHATE SALT, AND METHOD FOR MANUFACTURING HIGH PURITY RIVAROXABAN USING SAME
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Paragraph 0058-0063, (2017/12/15)
The present invention relates to a method of producing 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl}-methyl)-2-thiophene carboxamide (hereinafter, andPrime;rivaroxabanandPrime;, chemical formula 1) with high purity in an economical and mass-producible manner by using novel 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}morpholine-3-one disphosphate salts (hereinafter, andPrime;morpholine disphosphate saltsandPrime;, chemical formula 2).COPYRIGHT KIPO 2017
A method for synthesizing [...] (by machine translation)
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Paragraph 0116-0118; 0120; 0121, (2018/04/01)
The invention discloses a method for synthesizing [...], from 4 - (4 - a ammonia alkenyl phenyl) - 3 - morpholone with (S)- {1 - (chloromethane ester) - 2 - [2 - (1, 3 - two oxygen different indole) yl] ethyl} halide salt to ring-closure reaction, to make the key intermediate (S)- 2 - {[2 - oxo - 3 - (4 - (3 - oxo-morpholine) phenyl) oxazolidine - 5 - yl] methyl} isoindole - 1, 3 - dione, then the key intermediate to remove the amino protecting base 4 - {4 - [(5 S) - 5 - (aminomethyl) - 2 - oxo - 1, 3 - oxazolidine - 3 - yl] phenyl} morpholine - 3 - one hydrochloride, with 2 - chloro formyl - 5 - [...][...] further reaction. This invention prepares mild condition, the process is simple, low cost, high yield, is suitable for industrial production. (by machine translation)
A method for the preparation of key intermediate the advantage cuts down Sha Ban
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Paragraph 0020; 0047; 0048; 0049; 0050, (2017/08/25)
The invention relates to a preparation method of a rivaroxaban key intermediate, particularly a preparation method of 4-[4-[(5S)-5-(aminomethyl)-2-oxo-3-oxazolidinyl]phenyl]-3-morpholone hydrochloride (compound 4), which comprises the following steps: reacting dibenzyl ammonia with R-epoxy chloropropane to obtain N,N-dibenzyl epoxypropane (compound 1), reacting the compound 1 with 4-(4-aminophenyl)morpholinyl-3-one to obtain a compound 2, reacting the compound 2 with N,N-carbonyl-diimidazole to obtain a compound 3, and catalyzing the compound 3 with palladium on carbon to obtain the 4-[4-[(5S)-5-(aminomethyl)-2-oxo-3-oxazolidinyl]phenyl]-3-morpholone hydrochloride.
A process for preparing 4 - (4 - aminophenyl) - 3 - morpholinon method (by machine translation)
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, (2017/08/24)
The invention discloses a process for preparing 4 - (4 - aminophenyl) - 3 - morpholone (type IV) method, which belongs to the field of chemical synthesis. The specific method comprises: intermediate N - (4 - aminophenyl) - 2 - (2 - halo ethoxy) acetamide (type III) by the one-step cyclization reaction systems benefit cuts down Sha Ban key intermediate 4 - (4 - aminophenyl) - 3 - morpholone (type IV), wherein X represents halogen. The prepared 4 - (4 - aminophenyl) - 3 - morpholinon purity is good, the reaction yield is high, can be as high as 87% of the left and right, and the preparation process avoids the use of expensive metal palladium on nitro reduction, the operation is simple, and is suitable for industrial production. (by machine translation)