- Alluzole intermediate and method for preparing
-
The invention relates to an intermediate and a preparation method thereof, and adopts a compound as shown in a formula (4). For the preparation of, 4 is R in the formula (- COOR). 1 Or CONH2 , R1 Alkyl or aryl. The compound represented by the formula (4) is represented by the formula (3). Reaction of acyl chloride with acylating agent The acid chloride is then reacted with the thiocyanide to form. To the application, a new material formula (4) is used as an intermediate to synthesize the, and a brand new process route for synthesizing the is developed, and the process route is good in stability and good in repeatability, and is very suitable for industrial production.
- -
-
-
- Method for preparing
-
The invention relates to a method for preparing an intermediate and an epalutamide, wherein the compound is represented by the formula (5). The preparation method of the compound represented by the formula (5) comprises the following steps: preparing compound represented by formula (3) by using the compound as an intermediate. Compound of formula (4) and Thithio reagent is reacted to form the compound represented by formula (5). The thio reagent is a phenyl thioformate. A combination of one or more N-thiocarbonyldiimidazole, 1,1 -thiocarbonyl DI-2 (1H) - pyridine. The inventors have found that 4 - (1 - carboxamide - cyclobutylamino) -2 - fluoro - N - methyl - benzamide, 5 - amino -2 - cyano -3 - trifluoromethyl pyridine and sodium thiochloroformate can be obtained in a higher yield than the prior art by one-step reaction under appropriate conditions. Based on this finding, the present invention was obtained and presented by further study.
- -
-
-
- Method for synthesizing apalutamide and intermediate thereof and intermediate
-
The invention discloses a preparation method of Boc-apalutamide, wherein the method comprises the steps: under the catalytic action of a catalyst, reacting 6-thio-5,7-diazaspiro[3.4]octyl-8-one with N-(4-bromo-2-fluorobenzoyl)tert-butyl carbamate, and reacting with 2-cyano-3-trifluoromethyl-5-bromopyridine to obtain Boc-apalutamide. According to the invention, 6-thio-5,7-diazaspiro[3.4]octyl-8-oneis used as a substrate, and Boc-apalutamide: N-(4-(7-(6-cyan-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thio-5,7-diazaspiro[3.4]-5-octyl)-2-fluorobenzoyl)-N-methyl tert-butyl carbamate can be directly obtained by a one-pot method. And the final product apalutamide can be obtained through a simple Boc removal reaction. The process is simple in steps and suitable for industrial mass production.
- -
-
-
- PROCESS FOR THE PREPARATION OF APALUTAMIDE
-
Aspect of the present application relates to process for the preparation of crystalline form of Apalutamide and process for the preparation of Apalutamide in the presence of neutralizing agent selected from triethylsilylchloride, trimethylsilyl chloride, zinc chloride, aluminium chloride, iron chloride, sodium chloride, acetic acid, ammonium chloride or mixture thereof followed by treating with acid to obtain Apalutamide.
- -
-
Paragraph 11-12
(2021/02/26)
-
- Process for the preparation of 4-[7-(6-Cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7- diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide and its polymorphs
-
The present application relates a process for the preparation of 4- [7 - (6-Cyano- 5- trifluoro methyl pyridin-3- yl) -8- oxo -6- thioxo- 5,7- diazaspiro [3.4] oct-5- yl]- 2-fluoro-N-methyl benzamide of formula-1. The present application further discloses a processes for the preparation of amorphous and crystalline form of compound of formula-1. Formula-1.
- -
-
Page/Page column 10-13; 16
(2021/06/22)
-
- Benzamide compound and preparation method thereof, and application of benzamide compound in pharmacy
-
The invention discloses a benzamide compound and a preparation method, and application of the benzamide compound in pharmacy. The benzamide compound is a compound shown as a formula A which is described in the specification. In the formula M, when X is O,
- -
-
Paragraph 0173-0176
(2020/11/01)
-
- Pyrithiourea derivative as well as preparation method and application thereof
-
The invention belongs to the field of medical chemistry. The invention particularly relates to a pyrithiourea derivative as well as a preparation method and application thereof. The preparation methodcomprises the following steps: taking 2-cyano-3-trifluo
- -
-
-
- PROCESS FOR PREPARATION OF APALUTAMIDE
-
The present invention relates to a process for the preparation of apalutamide. In particular, the present invention relates to a process for the preparation of apalutamide and its intermediates. The present invention also relates to pharmaceutical compositions comprising apalutamide.
- -
-
Paragraph 0101; 0103; 0104; 0108; 0110
(2020/02/10)
-
- Apalutamide synthetic method and intermediate
-
The invention provides a novel preparation method of Apalutamide. According to the novel preparation method, 2-fluoro-4-bromo-N-methyl benzene methanamine amide, 1-amino cyclobutyl carboxylate hydrochloride, and the like are taken as initial raw materials, and substitution reaction is carried out so as to obtain 1-((3-fluoro-4-(methyl carbamyl)phenyl)amino) cyclobutane-1-carboxylic acid, wherein synthesis yield is higher than 70%, and purity is higher than 97.2%; then esterification is carried out so as to obtain 1-((3-fluoro-4-(methyl carbamyl)phenyl)amino) cyclobutane-1-carboxylic ester, wherein synthesis yield is higher than 83%, and purity is higher than 97.8%; and at last, ring closing reaction with 2-cyan-3-trifluoromethyl-5-isothiocyano pyridine is carried out so as to obtain Apalutamide, wherein yield is higher than 68%, and purity is higher than 98.1%. The preparation method possesses following advantages: the raw materials are easily available; technology is simple; operationis convenient; yield is high; and cost is low.
- -
-
Paragraph 0100; 0101
(2019/08/12)
-
- Processes for the Preparation of Apalutamide and Intermediates Thereof
-
The present invention provides processes for the preparation of Apalutamide (1), as well as intermediates useful in the preparation thereof. In particular, the process of the invention utilizes the intermediate compound of Formula (2), wherein G is OH or a leaving group, which provides improvements over the known processes for the preparation of Apalutamide (1).
- -
-
-
- Method for synthesizing apalutamide and intermediate thereof
-
The invention discloses a method for synthesizing apalutamide. The method includes carrying out condensation on N-methyl-2-fluorine-4-halogenated-benzamide compounds 1 and amino-1-cyclobutanecarboxylic acid hydrochloride 2 by means of Ullmann reaction to obtain to obtain intermediate compounds 3 and esterifying the intermediate compounds 3 to obtain intermediate compounds 4; carrying out cyclization by means of reaction on the intermediate compounds 4 and thiocyanide to obtain compounds 5; carrying out condensation by means of coupling the compounds 5 to obtain the apalutamide. The N-methyl-2-fluorine-4-halogenated-benzamide compounds 1 and the amino-1-cyclobutanecarboxylic acid hydrochloride 2 are used as starting materials. A path is shown, an R in the path represents alkyl, includes butis not limited to methyl or ethyl. The method has the advantages that route steps can be shortened to a great extent, the route efficiency can be improved, precious metal catalysts are omitted, and accordingly the process cost can be lowered; byproduct generation can be reduced, and accordingly the method is favorable for improving the purity of ultimate products.
- -
-
Paragraph 0050-0052
(2018/09/08)
-
- Preparation method of diaryl phenylthiohydantoin compound and intermediate of diaryl phenylthiohydantoin compound
-
The invention discloses a preparation method of a diaryl phenylthiohydantoin compound and an intermediate of the diaryl phenylthiohydantoin compound. The invention provides the preparation method of the diaryl phenylthiohydantoin compound which is as shown in a formula 1. The preparation method comprises the following steps: carrying out cyclization reaction on a compound 2 and a compound 3 in a solvent, thus obtaining a compound 1. The preparation method disclosed by the invention is safe in operation, low in cost and high in yield. (The formula 1 is shown in the description).
- -
-
Paragraph 0166-0170
(2018/07/03)
-
- Preparation method for apalutamide and intermediate of apalutamide
-
The invention provides a preparation method for apalutamide and an intermediate of apalutamide. The preparation method provided by the invention comprises the following steps: subjecting a compound asshown in a formula IV which is described in the specification or an acid addition salt thereof and a compound as shown in a formula III which is described in the specification to a condensation reaction so as to prepare the intermediate, i.e., a compound as shown in a formula II which is described in the specification; and reacting the compound as shown in the formula II with a compound TFP-6 soas to prepare apalutamide. The preparation method provided by the invention can avoid usage of dangerous compounds like cyanide and is very suitable for industrial production.
- -
-
-
- PROCESS FOR PREPARING APALUTAMIDE
-
The present invention provides efficient, economical, and environmentally friendly processes for synthesizing apalutamide and intermediates thereof. Also provided herein are novel compounds and intermediates thereof.
- -
-
-
- SOLID STATE FORMS OF APALUTAMIDE
-
Disclosed are solid state forms of Apalutamide and salts thereof, processes for preparation thereof and pharmaceutical compositions thereof.
- -
-
-
- Novel synthesis method for Apalutamide
-
The invention relates to a novel synthesis method for Apalutamide. The novel synthesis method comprises the following steps: enabling 1-aminocyclobutanecarboxylic acid and 4-bromo-2-fluoro-N-methylbenzamide to react, so as to obtain 4-(1-carboxyl-cyclobutylamino)-2-fluoro-N-methyl-benzamide; enabling the 4-(1-carboxyl-cyclobutylamino)-2-fluoro-N-methyl-benzamide, 5-amino-3-trifluoromethyl-2-cyanopyridine and thio-phosgene to react, so as to obtain the product. In the overall production process, raw materials like sodium cyanide or potassium cyanide are not required to be used, so that safety accidents caused by toxic raw materials are avoided; meanwhile, the 1-aminocyclobutanecarboxylic acid is stable in properties, refining is easier to perform compared with a cyclobutanone process, and a synthesized final product has few other impurities; with the method, the cost can be reduced by over 35 percent, so that the method is beneficial to market popularization and the majority of patients.
- -
-
Paragraph 0016; 0030
(2018/01/11)
-
- Design, synthesis, and biological evaluation of deuterated apalutamide with improved pharmacokinetic profiles
-
A series of deuterated apalutamide were designed and prepared. Compared to its prototype compound 18, deuterated analogues 19 and 21 showed obviously higher plasma concentrations and better PK parameters after oral administration in mice. In rats, N-trideuteromethyl compound 19 displayed 1.8-fold peak concentration (Cmax), and nearly doubled its drug exposure in plasma (AUC0–∞) compared to compound 18. Unsurprisingly, compounds 18 and 19 had similar affinity for AR in vitro. In summary, the deuteration strategy could obviously improve PK parameters of apalutamide.
- Pang, Xuehai,Wang, Yingwei,Chen, Yuanwei
-
p. 2803 - 2806
(2017/05/29)
-
- Substituted diazaspiroalkanes as androgen receptor modulators
-
This invention provides for compounds of the Formula II: wherein A, B, Het, R1, R2 and R3 are as described herein. These compounds are androgen receptor modulators useful for the treatment of androgen receptor-associated conditions.
- -
-
-
- ANDROGEN RECEPTOR MODULATOR FOR TREATMENT OF PROSTATE CANCER AND ANDROGEN RECEPTOR-ASSOCIATED DISEASES
-
PROBLEM TO BE SOLVED: To provide a series of compounds that modulate the function of the nuclear hormone receptors, especially the androgen receptor. SOLUTION: The present invention relates to hydantoin compounds, methods of using such compounds in the treatment of androgen receptor-associated conditions, such as age-related diseases, for example, prostate cancer, and to pharmaceutical compositions containing such compounds. In an embodiment, a pharmaceutical composition includes a therapeutically effective amount of a compound according to the formula II, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, or adjuvant. The present invention provides a series of compounds that modulate the function of the nuclear hormone receptors, especially the androgen receptor. These compounds can cause disappearance of prostate cancer cells and tumors. COPYRIGHT: (C)2016,JPOandINPIT
- -
-
-
- IMIDAZOLE DIKETONE COMPOUND AND USE THEREOF
-
Provided are imidazolidinedione compounds of formula (I), processes for preparation, uses and pharmaceutically compositions thereof. Said imidazolidinedione compounds possess androgen receptor antagonist activity and can be used for preventing and treating diseases and disorders related to androgen receptor, such as prostate cancer, alopecia, hair regeneration, acne and adolescent acne.
- -
-
-
- PROCESSES FOR THE PREPARATION OF A DIARYLTHIOHYDANTOIN COMPOUND
-
Disclosed are processes and intermediates for the preparation of compound (X), which is currently being investigated for the treatment of prostate cancer.
- -
-
-
- ANDROGEN RECEPTOR ANTAGONISTS
-
Disclosed herein are compositions and methods for modulating the androgen receptor.
- -
-
Paragraph 0327
(2016/04/26)
-
- SYNTHESIS OF THIOHYDANTOINS
-
A novel synthesis of the anti-androgen, A52, which has been found to be useful in the treatment of prostate cancer, is provided. A52 as well as structurally related analogs may be prepared via the inventive route. This new synthetic scheme may be used to prepare kilogram scale quantities of pure A52.
- -
-
-
