830346-49-1

Basic information

• Product Name: Carbamic acid, N-[(1R)-2-[5-bromo-3-[[2-fluoro-6-(trifluoromethyl)phenyl]methyl]-3,6-dihydro-4-methyl-2,6-dioxo-1(2H)-pyrimidinyl]-1-phenylethyl]-, 1,1-dimethylethyl ester
• Synonyms: Carbamic acid, N-[(1R)-2-[5-bromo-3-[[2-fluoro-6-(trifluoromethyl)phenyl]methyl]-3,6-dihydro-4-methyl-2,6-dioxo-1(2H)-pyrimidinyl]-1-phenylethyl]-, 1,1-dimethylethyl ester;N-[(1R)-2-[5-Bromo-3-[[2-fluoro-6-(trifluoromethyl)phenyl]methyl]-3,6-dihydro-4-methyl-2,6-dioxo-1(2H)-pyrimidinyl]-1-phenylethyl]carbamic acid 1,1-dimethylethyl ester
• CAS NO: 830346-49-1
• Molecular Formula: C₂₆H₂₆BrF₄N₃O₄
• Molecular Weight: 602.4158328
• Mol File: 830346-49-1.mol

Chemical Properties

• Appearance: /
• Density: 1.446g/cm³
• Refractive Index: 1.56
• Storage Temp.: -20°C Freezer, Under inert atmosphere
• Solubility: Methanol; Ethyl Acetate; Dichloromethane
• PKA: 11.50±0.46(Predicted)
• CAS DataBase Reference: Carbamic acid, N-[(1R)-2-[5-bromo-3-[[2-fluoro-6-(trifluoromethyl)phenyl]methyl]-3,6-dihydro-4-methyl-2,6-dioxo-1(2H)-pyrimidinyl]-1-phenylethyl]-, 1,1-dimethylethyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: Carbamic acid, N-[(1R)-2-[5-bromo-3-[[2-fluoro-6-(trifluoromethyl)phenyl]methyl]-3,6-dihydro-4-methyl-2,6-dioxo-1(2H)-pyrimidinyl]-1-phenylethyl]-, 1,1-dimethylethyl ester(830346-49-1)
• EPA Substance Registry System: Carbamic acid, N-[(1R)-2-[5-bromo-3-[[2-fluoro-6-(trifluoromethyl)phenyl]methyl]-3,6-dihydro-4-methyl-2,6-dioxo-1(2H)-pyrimidinyl]-1-phenylethyl]-, 1,1-dimethylethyl ester(830346-49-1)

Safety Data

• Hazardous Substances Data: 830346-49-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Carbamic acid, N-[(1R)-2-[5-bromo-3-[[2-fluoro-6-(trifluoromethyl)phenyl]methyl]-3,6-dihydro-4-methyl-2,6-dioxo-1(2H)-pyrimidinyl]-1-phenylethyl]-, 1,1-dimethylethyl ester is used as an intermediate in the synthesis of Elagolix Methoxy-d3 Sodium Salt (E501024). Carbamic acid, N-[(1R)-2-[5-bromo-3-[[2-fluoro-6-(trifluoromethyl)phenyl]methyl]-3,6-dihydro-4-methyl-2,6-dioxo-1(2H)-pyrimidinyl]-1-phenylethyl]-, 1,1-dimethylethyl ester is a potent hGnRH-R antagonist, which has potential applications in the development of treatments for various hormonal disorders and conditions related to the gonadotropin-releasing hormone receptor.

InChI:InChI=1/C26H26BrF4N3O4/c1-15-21(27)22(35)34(14-20(16-9-6-5-7-10-16)32-23(36)38-25(2,3)4)24(37)33(15)13-17-18(26(29,30)31)11-8-12-19(17)28/h5-12,20H,13-14H2,1-4H3,(H,32,36)/t20-/m0/s1

Upstream product

• 830346-48-0 5-bromo-1-[2-fluoro-6-(trifluoromethyl)benzyl]-6-methylpyrimidine-2,4-(1H,3H)-dione 
• 67341-01-9 (R)-N-(tert-butoxycarbonyl)phenylglycinol 
• 352303-66-3 5-bromo-1-(2,6-difluoro-benzyl)-6-methyl-1H-pyrimidine-2,4-dione 
• 830346-47-9 1-[2-fluoro-6-(trifluoromethyl)benzyl]-6-methyl-2,4(1H,3H)-pyrimidinedione 
• 102089-75-8 (-)-(1R)-1-[(1',1'-dimethylethoxycarbonyl)amino]-2-(methylsulfonyl)oxy-1-phenylethane 
• 35809-67-7 (Z)-3-Phenoxycarbonylamino-but-2-enoic acid ethyl ester 
• 830346-46-8 N-{[2-fluoro-6-(trifluoromethyl)phenyl]methyl}urea 
• 239087-06-0 (2-fluoro-6-(trifluoromethyl) phenyl)methanamine 

Downstream Products

• 830346-51-5 (R)-(2-(5-(2-fluoro-3-methoxyphenyl)-3-(2-fluoro-6-(trifluoromethyl)benzyl)-4-methyl-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)-1-phenylethyl)carbamic acid tert-butyl ester 
• 1308380-86-0 {(R)-2-[5-(4-benzyl-3-hydroxymethyl-piperazin-1-yl)-3-(2-fluoro-6-trifluoromethyl-benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenyl-ethyl}-carbamic acid tert-butyl ester 
• 1308379-84-1 3-((R)-2-amino-2-phenyl-ethyl)-1-(2-fluoro-6-trifluoromethyl-benzyl)-5-[3-hydroxymethyl-4-(5-trifluoromethyl-furan-2-ylmethyl)-piperazin-1-yl]-6-methyl-1H-pyrimidine-2,4-dione 
• 1308380-87-1 {(R)-2-[3-(2-fluoro-6-trifluoromethyl-benzyl)-5-(3-hydroxymethyl-piperazin-1-yl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenyl-ethyl}-carbamic acid tert-butyl ester 
• 1308380-88-2 ((R)-2-{3-(2-fluoro-6-trifluoromethyl-benzyl)-5-[3-hydroxymethyl-4-(5-trifluoromethyl-furan-2-ylmethyl)-piperazin-1-yl]-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl}-1-phenyl-ethyl)-carbamic acid tert-butyl ester 
• 1308375-89-4 {(R)-2-[5-(4-benzyl-piperazin-1-yl)-3-(2-fluoro-6-trifluoromethyl-benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenyl-ethyl}-carbamic acid tert-butyl ester 
• 1308376-55-7 (R)-3-(2-amino-2-phenylethyl)-1-(2-fluoro-6-(trifluoromethyl)benzyl)-6-methyl-5-(4-(pyridin-3-ylmethyl)piperazin-1-yl)pyrimidine-2,4(1H,3H)-dione 
• 1308377-66-3 (R)-3-(2-amino-2-phenylethyl)-1-(2-fluoro-6-(trifluoromethyl)benzyl)-6-methyl-5-(4-((2-methylpyridin-3-yl)methyl)piperazin-1-yl)pyrimidine-2,4(1H,3H)-dione 
• 1308377-54-9 (R)-3-(2-amino-2-phenylethyl)-1-(2-fluoro-6-(trifluoromethyl)benzyl)-6-methyl-5-(4-((6-methylpyridin-3-yl)methyl)piperazin-1-yl)pyrimidine-2,4(1H,3H)-dione 
• 1308377-68-5 (R)-3-(2-amino-2-phenylethyl)-1-(2-fluoro-6-(trifluoromethyl)benzyl)-6-methyl-5-(4-((5-methylpyridin-3-yl)methyl)piperazin-1-yl)pyrimidine-2,4(1H,3H)-dione 
• 1308377-51-6 (R)-3-(2-amino-2-phenylethyl)-1-(2-fluoro-6-(trifluoromethyl)benzyl)-5-(4-((2-fluoropyridin-3-yl)methyl)piperazin-1-yl)-6-methylpyrimidine-2,4(1H,3H)-dione 
• 1308376-59-1 (R)-3-(2-amino-2-phenylethyl)-1-(2-fluoro-6-(trifluoromethyl)benzyl)-5-(4-((5-fluoropyridin-3-yl)methyl)piperazin-1-yl)-6-methylpyrimidine-2,4(1H,3H)-dione 
• 1308377-62-9 (R)-3-(2-amino-2-phenylethyl)-5-(4-((2-chloropyridin-3-yl)methyl)piperazin-1-yl)-1-(2-fluoro-6-(trifluoromethyl)benzyl)-6-methylpyrimidine-2,4(1H,3H)-dione 
• 1308377-65-2 (R)-3-(2-amino-2-phenylethyl)-5-(4-((6-chloropyridin-3-yl)methyl)piperazin-1-yl)-1-(2-fluoro-6-(trifluoromethyl)benzyl)-6-methylpyrimidine-2,4(1H,3H)-dione 

Relevant articles and documents

AN IMPROVED PROCESS FOR THE PREPARATION OF 4-({(1 R)-2-[5-(2-FLUORO-3METHOXYPHENYL)-3-{[2-FLUORO-6-(TRIFLUORO METHYL) PHENYL]METHYL}-4-METHYL-2,6-DIOXO-3,6DIHYDROPYRIMIDIN-1(2 H)-YL]-1-PHENYLETHYL}AMINO)BUTANOIC ACID OR ITS PHARMACEUTICALLY ACCEPTABLE SALTS

The present invention relates to an improved process for the preparation of 4- ({(1R) -2- [5- (2-fluoro- 3- methoxy phenyl) – 3 - {[ 2-fluoro- 6-(trifluoro methyl) phenyl] methyl} -4-methyl- 2,6-dioxo- 3,6-dihydropyrimidin-1(2H)-yl]-1-phenylethyl}amino) butanoic acid of formula (I) or its pharmaceutically acceptable salts. The compound of formula (I) is represented by the following structural formula.

PROCESS FOR THE SYNTHESIS OF THE SODIUM SALT OF 4-[[(LR)-2-[5-(2-FLUORO-3-METHOXYPHENYL)-3-[[2-FLUORO-6-(TRIFLUOROMETHYL)-PHENYL]METHYL]-3,6-DIHYDRO-4-METHYL-2,6-DIOXO-L(2H)-PYRIMIDINYL]-L- PHENYLETHYL]AMINO]-BUTANOIC ACID (ELAGOLIX SODIUM SALT) AND INTER

The present invention relates to a process for the preparation of the sodium salt of 4-[[(1R)-2-[5-(2-fluoro-3-methoxyphenyl)-3-[[2-fluoro-6-(trifluoromethyl)phenyl]methyl]-3,6-dihydro-4-methyl-2,6-dioxo-l(2H)-pyrimidinyl]-l-phenylethyl]-amino]-butanoic a

Oxagolix intermediate, and preparation method and application thereof

The invention provides a preparation method of a novel oxagolix important intermediate compound 1, and also provides two novel intermediate compounds 5 and 6. By starting from the novel intermediate compound 5, the five-step synthesis in the prior art is

Substituted pyrimidine-2, 4(1H, 3H)-dione derivative and uses thereof

The invention belongs to the technical field of medicines, and relates to a substituted pyrimidine-2, 4(1H, 3H)-dione derivative and uses thereof, and a pharmaceutical composition containing the compound. The derivative and the pharmaceutical composition can be used as gonadotropin releasing hormone receptor antagonists. The invention also relates to a method for preparing the compound and the pharmaceutical composition, and uses of the compound and the pharmaceutical composition in prevention or treatment of sex hormone dependent diseases including but not limited to prostate cancer, endometriosis, hysteromyoma, precocious puberty and the like.

PROCESS FOR THE PREPARATION OF ELAGOLIX SODIUM AND INTERMEDIATES THEREOF

The present invention relates to compounds of Formula A, isomers, polymorphs and process of preparation thereof, wherein, S is a pharmaceutically acceptable salt, R is selected from hydrogen or C1-C3 alkyl group substituted with Rsu

PROCESS FOR PREPARING ELAGOLIX

The application relates to a process for the preparation of compound of formula (1) or a salt thereof (i.e. elagolix): The application also relates to solid crystalline forms of intermediates used in the process.

Discovery of sodium R-(+)-4-{2-[5-(2-Fluoro-3-methoxyphenyl)-3-(2-fluoro-6- [trifluoromethyl]-benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl] -1-phenylethylamino}butyrate (elagolix), a potent and orally available nonpeptide antagonist of the human gonadotropin-releasing hormone receptor

The discovery of novel uracil phenylethylamines bearing a butyric acid as potent human gonadotropin-releasing hormone receptor (hGnRH-R) antagonists is described. A major focus of this optimization was to improve the CYP3A4 inhibition liability of these uracils while maintaining their GnRH-R potency. R-4-{2-[5-(2-Fluoro-3-methoxyphenyl)-3-(2-fluoro-6-[trifluoromethyl]benzyl) -4-methyl-2,6-dioxo-3,6-dihy-dro-2H-pyrimidin-1-yl]-1-phenylethylamino}butyric acid sodium salt, 10b (elagolix), was identified as a potent and selective hGnRH-R antagonist. Oral administration of 10b suppressed luteinizing hormone in castrated macaques. These efforts led to the identification of 10b as a clinical compound for the treatment of endometriosis.

GONADOTROPIN-RELEASING HORMONE RECEPTOR ANTAGONISTS AND METHODS RELATING THERETO

GnRH receptor antagonists are disclosed that have utility in the treatment of a variety of sex-hormone related conditions in both men and women. The compounds of this invention have the structure: wherein n, R1a, R1b, R1c, R2a, R2b, R3, R4, R5, R6 and X are as defined herein, including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for antagonizing gonadotropin-releasing hormone in a subject in need thereof.

PYRIMIDINE-2,4-DIONE DERIVATIVES AS GONADOTROPIN-RELEASING HORMONE RECEPTOR ANTAGONISTS

GnRH receptor antagonists are disclosed that have utility in the treatment of a variety of sex-hormone related conditions in both men and women. The compounds of this invention have the structure formula (I) wherein R1a, R1b, R2a, R2b, R3, R4, R5, R6, R7 and X are as defined herein, including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for antagonizing gonadotropin-releasing hormone in a subject in need thereof.

PYRIMIDINE-2, 4-DIONE DERIVATIVES AS GONADOTROPIN-RELEASING HORMONE RECEPTOR ANTAGONISTS

GnRH receptor antagonists are disclosed that have utility in the treatment of a variety of sex-hormone related conditions in both men and women. The compounds of this invention have the structure: wherein R1a, R1b, R1c, R2a, R2b, R3, R4, R5, R6 and X are as defined herein, including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for antagonizing gonadotropin-releasing hormone in a subject in need thereof.