1166397-39-2

Upstream product

• 959709-83-2 (4S,5S)-N-cyclopropyl-2-methyl-4-propyl-4,5-dihydro-1,3-oxazole-5-carboxamide 
• 928-95-0 (E)-2-Hexen-1-ol 
• 111003-36-2 ((2R,3S)-3-propyloxiran-2-yl)methanol 
• 92418-71-8 (2R,3R)-2,3-epoxy-1-hexanol 
• 608520-05-4 (3R,2S)-3-propyloxirane-2-carboxylic acid 
• 959709-86-5 methyl (2S,3S) 3-amino-2-hydroxyhexanoate hydrochloride salt 
• 765-30-0 Cyclopropylamine 
• 67271-32-3 ethyl 2-chloro-3-oxohexanoate 
• 3249-68-1 ethyl butyroyl acetate 
• 166196-06-1 3-tert-butoxycarbonylamino-2-hydroxyhexanoic acid 
• 367258-42-2 2-hydroxy-3-nitrohexanoic acid 
• 166196-05-0 3-amino-2-hydroxyhexanoic acid 
• 959709-91-2 (4S,5S)-N-cyclopropyl-2-isopropyl-4-propyl-4,5-dihydro-1,3-oxazole-5-carboxamide 
• 944716-71-6 (2S,3S)-N-cyclopropyl-3-(tert-butoxycarbonyl)amino-2-hydroxyhexanoic acid amide 

Downstream Products

• 402959-36-8 C₃₆H₅₅N₇O₆ 
• 402957-28-2 (1S,3aR,6aS)-2-((S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetamido)-3,3-dimethylbutanoyl)-N-((S)-1-(cyclopropylamino)-1,2-dioxohexan-3-yl)octahydrocyclopenta[c]pyrrole-1-carboxamide 

Relevant academic research and scientific papers

Azetidines and spiro azetidines as novel P2 units in hepatitis C virus NS3 protease inhibitors

Herein, we report the synthesis and structure-activity relationship studies of new analogs of boceprevir 1 and telaprevir 2. Introduction of azetidine and spiroazetidines as a P2 substituent that replaced the pyrrolidine moiety of 1 and 2 led to the disco

Asymmetric synthesis of 3,4-disubstituted proline derivatives: Application in synthesis of hepatitis C virus protease inhibitor telaprevir

A practical asymmetric synthesis of 3,4-disubstituted proline derivatives has been realized with high stereoselectivity and moderate yield. The key steps involved are desymmetric ring-opening reaction of commercially available anhydrides, intramolecular Strecker reaction and thermodynamically controlled cyanide hydrolysis. Based on this methodology, the synthesis of HCV protease inhibitor Telaprevir was achieved.

A pulls Swiss Wei intermediates for the synthesis of the new method

The invention discloses a method for preparing (3S)-3-amino-2-hydroxyl-N-cyclopropylhexanamide. The compound can be used as an important intermediate for preparing telaprevir. According to the invention, ethyl butyrylacetate is used as a starting raw material, and through steps of helogenation, substitution, amination, reduction, hydrolysis, deprotection, resolution and the like, (3S)-3-amino-2-hydroxyl-N-cyclopropylhexanamide is prepared. The method provided by the invention has advantages as follows: raw materials are cheap and easily available; reaction yield is high; and costs are high.

PROCESS FOR PREPARING ALPHA-HYDROXY-BETA-AMINO ACID DERIVATIVES

The present invention relates to a method for producing (2S,3R) or (2R,3S) alpha-hydroxy-beta-sulfinamid derivative where a pure oxygen protection group is induced in an enantiomorphism type, and a method for producing (2S,3R)-3-amino-N-cyclopropyl-2-hydroxyhexanamide and an acceptable salt of the same or (2R,3S)-3- amino-N-cyclopropyl-2-hydroxyhexanamide and an acceptable salt of the same by using the same. The compound can be produced at high optical purity and high yield.COPYRIGHT KIPO 2015

SYNTHESIS OF AN INTERMEDIATE OF AN ANTIVIRAL COMPOUND

Process for the preparation of a cyclopropylamide compound which is useful as a structural unit in a process for the preparation of a viral protease inhibitor.

Synthesis of an intermediate of an antiviral compound

Process for the preparation of a cyclopropylamide compound (II) which is useful as a structural unit in a process for the preparation of a viral protease inhibitor.

Discovery of narlaprevir (SCH 900518): A potent, second generation HCV NS3 serine protease inhibitor

Boceprevir (SCH 503034), 1, a novel HCV NS3 serine protease inhibitor discovered in our laboratories, is currently undergoing phase III clinical trials. Detailed investigations toward a second generation protease inhibitor culminated in the discovery of narlaprevir (SCH 900518), 37, with improved potency (～10-fold over 1), pharmacokinetic profile and physicochemical characteristics, currently in phase II human trials. Exploration of synthetic sequence for preparation of 37 resulted in a route that required no silica gel purification for the entire synthesis.

Discovery of potent sulfonamide P4-capped ketoamide second generation inhibitors of hepatitis C virus NS3 serine protease with favorable pharmacokinetic profiles in preclinical species

Hepatitis is a disease characterized by inflammation of the liver, usually producing swelling and, in many cases, permanent damage to liver tissues. Viral hepatitis C (HCV), a small (+)-RNA virus, infects chronically 3% of the world's population. Boceprevir, SCH 503034, (1) our first generation HCV inhibitor, has already established proof-of- concept and is currently in late stage (phase III) clinical trials. In view of the positive data from our first generation compound, further work aimed at optimizing its overall profile was undertaken. Herein, we report that extension of our earlier inhibitor to the P4 pocket by introducing a new sulfonamide moiety and optimization of the P1/P1′ capping led to the discovery of a novel series of inhibitors of the HCV NS3 serine protease. Optimization of the P1 residue significantly improved potency and selectivity. The combination of optimal moieties led to the discovery of compound 47 which, in addition to being a potent inhibitor of HCV subgenomic RNA replication, was also found to have good PK profile in rat, dog and monkey.

PROCESS FOR PRODUCTION OF OPTICALLY ACTIVE 3-AMINO-2 -HYDROXYPROPIONIC CYCLOPROPYLAMIDE DERIVATIVES AND SALTS THEREOF

An objective of the present application is to provide an industrially practicable method for producing an optically-active 3-amino-2-hydroxypropionic cyclopropylamide derivative or salt thereof from an inexpensive easily-available starting material. The derivative or salt thereof is useful as an intermediate for a medicine. It is also intended by the present application to provide a useful intermediate of the derivative. The objective is attained by the following method. First, an easily-available 2-halo-3-oxopropionic acid derivative is asymmetrically reduced, and then epoxidated to produce an optically-active epoxycarboxylic acid derivative. Next, the derivative is converted into an optically-active epoxyamide derivative by reaction with cyclopropylamine, and then reacted with a nitrile to obtain an optically-active oxazolinamide derivative. Subsequently, selective acid solvolysis of the oxazoline skeleton gives the optically-active 3-amino-2-hydroxypropionic cyclopropylamide derivative or salt thereof.

Inhibitors of hepatitis C virus NS3/4A: α-Ketoamide based macrocyclic inhibitors

A novel series of hepatitis C virus (HCV) NS3/4A protease inhibitors bearing a P2-P4 macrocycle and a P1-P1′ α-ketoamide serine trap is reported. The NS3 protease, which is essential for viral replication, is considered one of the most attractive targets