74761-42-5

Basic information

• Product Name: (S)-2-((Methoxycarbonyl)aMino)-3-Methylbutanoic acid
• Synonyms: (S)-2-((Methoxycarbonyl)aMino)-3-Methylbutanoic acid;MOC-L-Valine;N-(Methoxycarbonyl)-L-valine;L-Valine, N-(Methoxycarbonyl)-;Moc-Val-OH;(2S)-2-[(Methoxycarbonyl)aMino]-3-Methylbutanoic acid;N-(methoxycarbonyl)-Valine;MOC-L-Val
• CAS NO: 74761-42-5
• Molecular Formula: C₇H₁₃NO₄
• Molecular Weight: 175.18242
• Product Categories: Pharmaceuticalintermediates
• Mol File: 74761-42-5.mol

Chemical Properties

• Melting Point: 109.0 to 113.0 °C
• Boiling Point: 315.9±25.0 °C(Predicted)
• Appearance: /
• Density: 1.154±0.06 g/cm3(Predicted)
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 4.44±0.10(Predicted)
• CAS DataBase Reference: (S)-2-((Methoxycarbonyl)aMino)-3-Methylbutanoic acid(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-2-((Methoxycarbonyl)aMino)-3-Methylbutanoic acid(74761-42-5)
• EPA Substance Registry System: (S)-2-((Methoxycarbonyl)aMino)-3-Methylbutanoic acid(74761-42-5)

Safety Data

• Hazardous Substances Data: 74761-42-5(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(S)-2-((Methoxycarbonyl)aMino)-3-Methylbutanoic acid is used as a Ledipasvir Intermediate for the development of antiviral medications, specifically targeting hepatitis C virus (HCV) infections. Its role in the synthesis of Ledipasvir contributes to the drug's efficacy in treating HCV by inhibiting the viral NS5A protein, thereby suppressing viral replication and assembly.
Used in Laboratory Research and Development:
(S)-2-((Methoxycarbonyl)aMino)-3-Methylbutanoic acid is utilized in laboratory settings for the synthesis and study of various organic compounds, including pharmaceuticals, agrochemicals, and other specialty chemicals. Its unique properties and reactivity make it a valuable tool for researchers in the development of new chemical entities and processes.
Used in Chemical Production Process:
(S)-2-((Methoxycarbonyl)aMino)-3-Methylbutanoic acid is employed in the chemical production process to synthesize a range of products, including pharmaceuticals, agrochemicals, and other specialty chemicals. Its versatility and reactivity in various chemical reactions make it an essential component in the manufacturing of these products.

Synthesis

Na2CO3 (1.83 g, 17.2 mmol) was added to an aq solution of NaOH (33 mL of 1 M/H2O, 33 mmol) and L-valine (3.900 g, 33.29 mmol) and the resulting solution was cooled with ice-water bath. Methyl chloroformate (2.8 mL, 36.1 mmol) was added dropwise, the cooling bath was removed and the reaction mixture was stirred at ambient temperature for 3.25 h. The reaction mixture was washed with ether (3x17 mL), and the aqueous phase was cooled with ice-water bath and acidified with conc HCl to a pH of 1-2, and extracted with CH2Cl2 (3x17 mL). The organic phase was dried (anhyd MgSO4), filtered, and concentrated in vacuo. Cap-1 as a white solid (5.00 g, 86%).

Upstream product

• 63-91-2 L-phenylalanine 
• 98807-38-6 Z-L-Val-O-COOMe 
• 112175-14-1 Moc-L-Val-O-COOMe 
• 72-18-4 L-valine 
• 79-22-1 methyl chloroformate 
• 13518-40-6 L-valine tert-butylester hydrochloride 
• 1208007-67-3 1,1-dimethylethyl (2S)-2-(5-bromo-1H-benzimidazol-2-yl)-1-pyrrolidinecarboxylate 
• 17498-50-9 L-valine hydrochloride 

Downstream Products

• 180462-96-8 N'-Cyclohexylmethyl-N'-[(2S,3S)-2-hydroxy-3-((S)-2-methoxycarbonylamino-3-methyl-butyrylamino)-4-phenyl-butyl]-hydrazinecarboxylic acid tert-butyl ester 
• 161968-14-5 1-[2(S)-hydroxy-3(S)-(N-(methoxycarbonyl)-(L)-valyl)amino-4-phenyl-butyl]-1-[cyclohexylmethyl]-2-[N-methoxycarbonyl-(L)-valyl]-hydrazine 
• 191594-68-0 N'-Biphenyl-4-ylmethyl-N'-[(2S,3S)-2-hydroxy-3-((S)-2-methoxycarbonylamino-3-methyl-butyrylamino)-4-phenyl-butyl]-hydrazinecarboxylic acid tert-butyl ester 
• 198905-15-6 N'-[(2S,3S)-2-Hydroxy-3-((S)-2-methoxycarbonylamino-3-methyl-butyrylamino)-4-phenyl-butyl]-N'-(4-pyridin-2-yl-benzyl)-hydrazinecarboxylic acid tert-butyl ester 
• 198904-60-8 N'-[(2S,3S)-2-Hydroxy-3-((S)-2-methoxycarbonylamino-3-methyl-butyrylamino)-4-phenyl-butyl]-N'-(4-thiazol-2-yl-benzyl)-hydrazinecarboxylic acid tert-butyl ester 
• 198904-49-3 N'-[(2S,3S)-2-Hydroxy-3-((S)-2-methoxycarbonylamino-3-methyl-butyrylamino)-4-phenyl-butyl]-N'-(4-thiazol-5-yl-benzyl)-hydrazinecarboxylic acid tert-butyl ester 
• 198903-87-6 ((S)-1-{(1S,2S)-1-Benzyl-2-hydroxy-3-[N'-((S)-2-methoxycarbonylamino-3-methyl-butyryl)-N-(4-thiazol-5-yl-benzyl)-hydrazino]-propylcarbamoyl}-2,2-dimethyl-propyl)-carbamic acid methyl ester 
• 198903-86-5 1-[4-(Thiazol-5-yl)-phenyl]-4(S)-hydroxy-5(S)-2,5-bis[N-(N-methoxycarbonyl-(L)-valyl)amino]-6-phenyl-2-azahexane 
• 198904-22-2 1-[4-(Pyridin-2-yl)-phenyl]-4(S)-hydroxy-5(S)-2,5-bis[N-(N-methoxycarbonyl-(L)-valyl)amino]-6-phenyl-2-azahexane 
• 872703-55-4 [(1S)-1-(N'-benzyl-hydrazinocarbonyl)-2-methyl-propyl]carbamic acid methyl ester 
• 1007885-17-7 4,4'-bis(2-((2S)-1-(N-(methoxycarbonyl)-L-valyl)-2-pyrrolidinyl)-1H-imidazol-5-yl)-2-biphenylcarboxylic acid 
• 144406-52-0 (S)-3-Methyl-2-{[1-phenyl-meth-(E)-ylidene]-amino}-butyric acid 2-((S)-3-methyl-2-{[1-phenyl-meth-(E)-ylidene]-amino}-butyryloxy)-ethyl ester 
• 144406-53-1 (S)-3-Methyl-2-{[1-phenyl-meth-(E)-ylidene]-amino}-butyric acid 3-((S)-3-methyl-2-{[1-phenyl-meth-(E)-ylidene]-amino}-butyryloxy)-propyl ester 
• 144406-54-2 (S)-3-Methyl-2-{[1-phenyl-meth-(E)-ylidene]-amino}-butyric acid 4-((S)-3-methyl-2-{[1-phenyl-meth-(E)-ylidene]-amino}-butyryloxy)-butyl ester 

Relevant articles and documents

Redesigning of the cap conformation and symmetry of the diphenylethyne core to yield highly potent pan-genotypic NS5A inhibitors with high potency and high resistance barrier

Herein, we report the discovery of several NS5A inhibitors with potency against HCV genotype 1b in the picomolar range. Compounds (15, 33) were of extremely high potency against HCV genotype 1b (EC50 ≈ 1 pM), improved activity against genotype 3a (GT 3a) and good metabolic stability. We studied the impact of changing the cap conformation relative to the diphenylethyne core and/or compound symmetry on both potency and metabolic stability. The analogs obtained exhibited improved potency against HCV genotypes 1a, 1b, 3a and 4a compared to the clinically approved candidate daclatasvir with EC50 values in the low picomolar range and SI50s > 7 orders of magnitude. Compound 15, a symmetrically m-, m’-substituted diphenyl ethyne analog, was 150-fold more potent than daclatasvir against GT 3a, while compound 33, an asymmetrically m-, p-substituted diphenyl ethyne analog, was 35-fold more potent than daclatasvir against GT 3a. In addition, compound 15 exhibited a higher resistance barrier than daclatasvir against genotype 1b.

Preparation process of amino acid N-carboxylic acid anhydride

The invention provides a preparation process of amino acid N-carboxylic acid anhydride, which comprises the following operations: amino acid and methyl chloroformate are used as starting raw materials to react under an alkaline condition to generate N-methoxycarbonyl-amino acid, and the N-methoxycarbonyl-amino acid is separated and purified under an acidic condition; dissolving the purified and dried N-methoxycarbonyl-amino acid in a solvent, mixing with a ring closing reagent thionyl chloride, and reacting at a certain reaction temperature to generate an amino acid N-carboxylic acid anhydride crude product; and adding a good solvent into the obtained amino acid N-carboxylic acid anhydride crude product, filtering to remove impurities, adding a poor solvent into the filtrate, recrystallizing under freezing, and drying to obtain the amino acid N-carboxylic acid anhydride (NCA). The preparation process is simple and convenient in method, easy to purify, stable in process, controllable in quality, low in anhydrous requirement on a reaction system, greatly improved in product yield, greatly reduced in reaction risk and suitable for industrial mass production.

Design and synthesis of novel symmetric fluorene-2,7-diamine derivatives as potent hepatitis C virus inhibitors

Hepatitis C virus (HCV) is an international challenge. Since the discovery of NS5A direct-acting antivirals, researchers turned their attention to pursue novel NS5A inhibitors with optimized design and structure. Herein we explore highly potent hepatitis C virus (HCV) NS5A inhibitors; the novel analogs share a common symmetrical prolinamide 2,7-diaminofluorene scaffold. Modification of the 2,7-diaminofluorene backbone included the use of (S)-prolinamide or its isostere (S,R)-piperidine-3-caboxamide, both bearing different amino acid residues with terminal carbamate groups. Compound 26 exhibited potent inhibitory activity against HCV genotype (GT) 1b (effective concentration (EC50) = 36 pM and a selectivity index of >2.78 × 106). Compound 26 showed high selectivity on GT 1b versus GT 4a. Interestingly, it showed a significant antiviral effect against GT 3a (EC50 = 1.2 nM). The structure-activity relationship (SAR) analysis revealed that picomolar inhibitory activity was attained with the use of S-prolinamide capped with R- isoleucine or R-phenylglycine residues bearing a terminal alkyl carbamate group.

NOVEL BENZIMIDAZOLE DERIVATIVES

The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit RNA-containing virus, particularly the hepatitis C virus (HCV). Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Compounds for inhibiting HCV (hepatitis C virus), pharmaceutical composition and application of compounds or pharmaceutical composition

The invention discloses compounds for inhibiting HCV (hepatitis C virus), pharmaceutical composition and an application of the compounds or the pharmaceutical composition. The compounds are compoundsshown in formula (I) or a stereoisomer, geometric isomer, a tautomer, an enantiomer, sulfur oxide, nitrogen oxide, hydrate, solvate, metabolite, pharmaceutically acceptable salt or prodrug of the compounds shown in formula (I); the compounds are effective antiviral drugs, especially can be used for inhibiting the function of NS5A protein encoded by the HCV, thereby effectively inhibiting the HCV.The method for preventing and/or treating drugs or diseases associated with the HCV by the compounds or the composition containing the new compounds has good market development prospects.

Monoglycosyl-containing heterocyclic compound for inhibiting hepatitis C viruses and preparation method

The invention discloses a monoglycosyl-containing heterocyclic compound for inhibiting hepatitis C viruses and a preparation method. The monoglycosyl-containing heterocyclic compound has a chemical structure represented by a formula I shown in the description. The monoglycosyl-containing heterocyclic compound disclosed by the invention can be used for effectively inhibiting protease of the hepatitis C viruses and treating infection of the hepatitis C viruses (HCV).

A novel, potent, and orally bioavailable thiazole HCV NS5A inhibitor for the treatment of hepatitis C virus

A medicinal chemistry program based on the small-molecule HCV NS5A inhibitor daclatasvir has led to the discovery of dimeric phenylthiazole compound 8, a novel and potent HCV NS5A inhibitor. The subsequent SAR studies and optimization revealed that the cycloalkyl amide derivatives 27a-29a exhibited superior potency against GT1b with GT1b EC50 values at picomolar concentration. Interestingly, high diastereospecificity for HCV inhibition was observed in this class with the (1R,2S,1′R,2′S) diastereomer displaying the highest GT1b inhibitory activity. The best inhibitor 27a was found to be 3-fold more potent (GT1b EC50 = 0.003 nM) than daclatasvir (GT1b EC50 = 0.009 nM) against GT1b, and no detectable in vitro cytotoxicity was observed (CC50 > 50 μM). Pharmacokinetic studies demonstrated that compound 27a had an excellent pharmacokinetic profiles with a superior oral exposure and desired bioavailability after oral administration in both rats and dogs, and therefore it was selected as a developmental candidate for the treatment of HCV infection.

5,5-FUSED ARYLENE OR HETEROARYLENE HEPATITIS C VIRUS INHIBITORS

Provided herein are 5,5-fused heteroarylene hepatitis C virus inhibitor compounds, for example, of Formula I, IA, or IB, pharmaceutical compositions comprising the compounds, and processes of preparation thereof. Also provided are methods of their use for the treatment of an HCV infection in a host in need thereof.

Highlights of the Structure-Activity Relationships of Benzimidazole Linked Pyrrolidines Leading to the Discovery of the Hepatitis C Virus NS5A Inhibitor Pibrentasvir (ABT-530)

Curative interferon and ribavirin sparing treatments for hepatitis C virus (HCV)-infected patients require a combination of mechanistically orthogonal direct acting antivirals. A shared component of these treatments is usually an HCV NS5A inhibitor. First generation FDA approved treatments, including the component NS5A inhibitors, do not exhibit equivalent efficacy against HCV virus genotypes 1-6. In particular, these first generation NS5A inhibitors tend to select for viral drug resistance. Ombitasvir is a first generation HCV NS5A inhibitor included as a key component of Viekira Pak for the treatment of patients with HCV genotype 1 infection. Since the launch of next generation HCV treatments, functional cure for genotype 1-6 HCV infections has been achieved, as well as shortened treatment duration across a wider spectrum of genotypes. In this paper, we show how we have modified the anchor, linker, and end-cap architecture of our NS5A inhibitor design template to discover a next generation NS5A inhibitor pibrentasvir (ABT-530), which exhibits potent inhibition of the replication of wild-type genotype 1-6 HCV replicons, as well as improved activity against replicon variants demonstrating resistance against first generation NS5A inhibitors.

Sulfur(vi) fluoride exchange as a key reaction for synthesizing biaryl sulfate core derivatives as potent hepatitis C virus NS5A inhibitors and their structure-activity relationship studies

Extremely potent, new hepatitis C virus (HCV) nonstructural 5A (NS5A) featuring substituted biaryl sulfate core structures was designed and synthesized. Based on the previously reported novel HCV NS5A inhibitors featuring biaryl sulfate core structures which exhibit two-digit picomolar half-maximal effective concentration (EC50) values against HCV genotype 1b and 2a, the new inhibitors equipped with the sulfate core structures containing diversely substituted aryl groups were explored. In this study, highly efficient, chemoselective coupling reactions between an arylsulfonyl fluoride and an aryl silyl ether, known as the sulfur(vi) fluoride exchange (SuFEx) reaction, were utilized. Among the inhibitors prepared based on the SuFEx chemistry, compounds 14, 15 and 29 exhibited two-digit picomolar EC50 values against GT-1b and single digit or sub nanomolar activities against the HCV GT-2a strain. Nonsymmetrical inhibitors containing an imidazole and amide moieties on each side of the sulfate core structures were also synthesized. In addition, a biotinylated probe targeting NS5A protein was prepared for labeling using the same synthetic methodology.