154333-29-6

Upstream product

• 2026-48-4 (S)-valinol 
• 100-52-7 benzaldehyde 
• 609-12-1 ethyl 2-bromoisovalerate 
• 10323-40-7 2-bromoisovaleric acid 
• 84984-06-5 dl-2-bromo-3-methyl-1-butanol 
• 82417-07-0 (1S,1'S)-(+)-N-(2'-hydroxy-1'-isopropylethyl)-1,2-diphenylethylamine 

Downstream Products

• 42807-42-1 N-benzyl-L-valinol 
• 1010385-10-0 (S)-3-methyl-2-((S)-1-phenylethylamino)butan-1-ol 
• 121328-42-5 (S)-3-methyl-2-((R)-1-phenylethylamino)butan-1-ol 
• 1004517-93-4 (S)-3-methyl-2-((S)-2-methyl-1-phenylpropylamino)butan-1-ol 
• 1198185-68-0 Benzyl (R)-3-(2-benzyloxycarbonylaminoethylsulfanyl)-2-[3-((9S,12R)-9-isopropyl-11-oxo-2,7-dioxa-10-azabicyclo[12.2.2]octadeca-1⁽¹⁷⁾,14⁽¹⁸⁾,15-trien-12-yl)ureido]propionate 
• 1198185-70-4 benzyl (R)-3-(2-benzyloxycarbonylaminoethanesulfonyl)-2-[3-((9S,12R)-9-isopropyl-11-oxo-2,7-dioxa-10-azabicyclo[12.2.2]octadeca-1⁽¹⁷⁾,14⁽¹⁸⁾,15-trien-12-yl)ureido]propionate 
• 1198186-02-5 benzyl ((8S,11R)-8-isopropyl-10-oxo-6-oxa-1,9,14-triazabicyclo[11.2.1]hexadeca-3,13⁽¹⁶⁾,14-trien-11-yl)carbamate 
• 1268883-26-6 (4S)-2-oxo-3-benzyl-4-isopropyl-1,2,3-oxathiazolidine 
• 1378857-37-4 C₁₂H₂₅NO 
• 1198186-00-3 benzyl [(R)-2-(1-allyl-1H-imidazol-4-yl)-1-((S)-1-allyloxymethyl-2-methylpropylcarbamoyl)ethyl]carbamate 
• 1198185-26-0 9H-fluoren-9-ylmethyl [(R)-1-[(S)-(1-allyloxymethyl-2-methylpropylcarbamoyl)]-2-(4-allyloxyphenyl)ethyl]carbamate 
• 84984-08-7 (1S,1'S)-(+)-N-(2'-hydroxy-1'-isopropylethyl)-1,2-diphenylethylamine hydrochloride 
• 158554-90-6 (S)-3-Benzyl-4-isopropyl-thiazolidine-2-thione 
• 873197-03-6 (2R,3S,4S)-(1-benzyl-2-cyano-4-isopropyl-azetidin-3-yl)-acetic acid ethyl ester 

Relevant academic research and scientific papers

Discovery of APD371: Identification of a Highly Potent and Selective CB2 Agonist for the Treatment of Chronic Pain

The discovery of a novel, selective and fully efficacious CB2 agonist with satisfactory pharmacokinetic and pharmaceutical properties is described. Compound 6 was efficacious in a rat model of osteoarthritis pain following oral administration and, in contrast to morphine, maintained its analgesic effect throughout a 5-day subchronic treatment paradigm. These data were consistent with our hypothesis that full agonist efficacy is required for efficient internalization and recycling of the CB2 receptor to avoid tachyphylaxis. Based on its overall favorable preclinical profile, 6 (APD371) was selected for further development for the treatment of pain.

MACROCYCLIC UREA AND SULFAMIDE DERIVATIVES AS INHIBITORS OF TAFIa

The invention relates to compounds of the formula (I) which are inhibitors of activated thrombin-activable fibrinolysis inhibitor. The compounds of the formula I are suitable for producing medicaments for prophylaxis, secondary prevention and treatment of one or more disorders associated with thromboses, embolisms, hypercoagulability or fibrotic changes.

Carbon dioxide as a carbonylating agent in the synthesis of 2-oxazolidinones, 2-oxazinones, and cyclic ureas: Scope and limitations

Carbon dioxide can be used as a convenient carbonylating agent in the synthesis of 2-oxazolidinones, 2-oxazinones, and cyclic ureas. The transient carbamate anion generated by treating a primary or secondary amine group in basic media can be activated with phosphorylating agents such as Diphenylphosphoryl azide (DPPA) and Diphenyl chlorophosphate (DPPCl) but also with other types of electrophiles such as SOCl2, TsCl, or AcCl. The intramolecular trapping of the activated carbamate by a hydroxyl group leads to the formation of 2-oxazolidinones or 2-oxazinones in good to excellent yields. This methodology was successfully applied to the synthesis of cyclic ureas up to 7-membered rings from the corresponding diamines.

PROCESS FOR PRODUCTION OF OPTICALLY ACTIVE FLUOROAMINE

Disclosed is a process for producing a protected optically active fluoroamine, which comprises the step of reacting an imine-protected optically active hydroxyamine, an oxazolidine-protected optically active hydroxyamine, or a mixture of the imine-protected optically active hydroxyamine and the oxazolidine-protected optically active hydroxyamine, with sulfuryl fluoride (SO2F2) in the presence of a tertiary amine having a carbon number of 7 to 18 (produced by substituting all of three hydrogen atoms in ammonia by alkyl groups). The desired optically active fluoroamine can be produced by hydrolyzing the protected optically active fluoroamine under acidic conditions.

Alternative and complementary approaches to the asymmetric synthesis of C3 substituted NH free or N-substituted isoindolin-1-ones

Complementary synthetic approaches to enantiomerically pure C3 alkylated or arylated NH free or N-substituted isoindolinones have been developed. The key step is elaboration of diversely substituted 2-alkyl- and arylbenzylamines, which can be submitted to a bis-metallation process followed by interception with a carbonylating agent. They can be also converted into N-alkylbromobenzylcarbamates or into bromobenzyldicarbamates and the assembly of the titled compounds can be readily ensured by reliance upon the Parham cyclization process.

Stereocontrolled synthesis of 3-substituted azetidinic amino acids

A set of enantiomerically pure N-disubstituted β-amino alcohols was chlorinated by treatment with thionyl chloride. This reaction gave a mixture of regioisomeric chlorides that could be equilibrated to the more stable regioisomer by heating in DMF. The chlorides thus obtained were engaged in an intramolecular anionic ring-closure and gave access to fully protected enantio- and diastereomerically pure 2,3-cis-disubstituted azetidinic amino acids. One of the latter was deprotected and included in a short peptide sequence. Georg Thieme Verlag Stuttgart.

Asymmetric reduction of acetophenone using lithium aluminium hydride modified with some novel amino alcohol Schiff bases

Some new chiral Schiff bases have been prepared in good yields from various carbonyl groups and two 2-amino alcohols. LiAlH4 was treated with different equivalents of the Schiff bases. Enantioselective reduction of acetophenone is achieved in h

Azetidinic amino acids: Stereocontrolled synthesis and pharmacological characterization as ligands for glutamate receptors and transporters

A set of ten azetidinic amino acids, that can be envisioned as C-4 alkyl substituted analogues of trans-2-carboxyazetidine-3-acetic acid (t-CAA) and/or conformationally constrained analogues of (R)- or (S)-glutamic acid (Glu) have been synthesized in a diastereo- and enantiomerically pure form from ss-amino alcohols through a straightforward five step sequence. The key step of this synthesis is an original anionic 4-exo-tet ring closure that forms the azetidine ring upon an intramolecular Michael addition. This reaction was proven to be reversible and to lead to a thermodynamic distribution of two diastereoisomers that were easily separated and converted in two steps into azetidinic amino acids. Azetidines 35-44 were characterized in binding studies on native ionotropic Glu receptors and in functional assays at cloned metabotropic receptors mGluR1, 2 and 4, representing group I, II and III mGlu receptors, respectively. Furthermore, azetidine analogues 35, 36 and 40 were also characterized as potential ligands at the glutamate transporter subtypes EAAT1-3 in the FLIPR Membrane Potential (FMP) assay. The (2R)-azetidines 35, 37, 39, 41 and 43 were inactive in iGlu, mGlu and EAAT assays, whereas a marked change in the pharmacological profile at the iGlu receptors was observed when a methyl group was introduced in the C-4 position, compound 36 versus t-CAA. At EAAT1-3, compound 35 was inactive, whereas azetidines 36 and 40 were both identified as inhibitors and showed selectivity for the EAAT2 subtype. The Royal Society of Chemistry 2005.

Preparation of chiral heterocyclic esters of β-amino acids

Chiral β-amino alcohols were successively prone to N-benzylation, O-allylation and oxidation of the resulting benzylamino group to give nitrones 3 which on hydrolysis afforded chiral hydroxylamines HO-NH-CH(R)-CH2-O-CH2-CH=CH2 ((S)-4: R = Me, Bn, iPr, (R)-4: R = Et). Swern oxidation of methyl 2,2-dimethyl-3-hydroxypropionate (16) and treatment of the resulting aldehyde 17 with hydroxylamines (S)-4b (R = Bn) or (R)-4d (R = Et) provided nitrones 18 that underwent an intramolecular 1,3-dipolar cycloaddition on heating yielding the bicyclic β-amino-acid esters 19b and ent-19d, respectively. Reductive cleavage of the N,O-bond of compounds 19 afforded the eight-membered ring compounds 20b and ent-20d, respectively. N-Benzylalaninol (22) was treated with β-bromo-methacrylate to give the amino alcohol 23. Swern oxidation and subsequent treatment with N-tert-butylhydroxylamine provided the bicyclic ester 26a (R = t-Bu) via the corresponding nitrone 24. Oxime 25 was prepared in an analogous way as 24 with unsubstituted hydroxylamine. It underwent an intramolecular 1.3-dipolar cycloaddition yielding 26b on heating in toluene. Reduction of 26a afforded the pyrrolidine-carboxylic ester 27a.

Synthesis and pyrolytic behaviour of thiazolidin-2-one 1,1-dioxides

Four examples of the chiral thiazolidin-2-one 1,1-dioxides 5 have been prepared by reaction of the appropriate amino alcohols 11 with CS2 in aqueous sodium hydroxide to give the thiazolidine-2-thiones 12, followed by oxidation with KMnO4 under phase-transfer conditions in the presence of benzoic acid, either directly or via the thiazolidin-2-ones 13. Upon flash vacuum pyrolysis (FVP) at 650°C, 5a-c decompose mainly by loss of SO2 to give an alkene and benzyl isocyanate together with other products from fragmentation of the N-benzyl group. A significant minor pathway involves net loss of CO2 and water to give the 2-phenyl-4,5-dihydrothiazoles 21 together with their aromatisation products 22 and 23. A mechanism for this new heterocyclic transformation is proposed involving initial expansion to a cyclic carbamic-sulnnic anhydride (2,1,4-oxathiazin-3-one 1-oxide). The fully assigned 13C NMR spectra are presented for 5, 12 and 13 and the 33S NMR spectrum has been obtained for 5c.