138231-07-9

Upstream product

• 100-52-7 benzaldehyde 
• 17342-08-4 (S)-Pyroglutaminol 
• 98-79-3 L-Pyroglutamic acid 
• 7149-65-7 ethyl (S)-pyroglutamate 
• 74-88-4 methyl iodide 
• 103201-79-2 (3R,7aS)-3-phenyl-tetrahydro-pyrrolo[1,2-c]oxazol-5-one 

Downstream Products

• 189618-78-8 N-methyl-3,5-dimethylpyrrolidin-2-one 
• 138231-08-0 <3R-(3α,6α,7aα)>-6-methyl-3-phenyl-3H,5H-tetrahydropyrrolo<1,2-c>oxazol-5-one 
• 180780-71-6 (2S,3S,4S)-2,3-Bis-benzyloxy-4-dimethylamino-5-methoxy-pentanoic acid [(1R,3S)-3-(4-chloromethyl-oxazol-2-yl)-1-methyl-butyl]-amide 
• 138078-58-7 (3S,5S)-5-(hydroxymethyl)-3-methyl-2-pyrrolidinone 

Relevant academic research and scientific papers

Stereoselective methylations of bicyclic lactams derived from pyroglutamic acid

Reaction of the lithium enolate of (-)7 with iodomethane provides a stereoselective synthesis of (2R,4S)-4-amino-2-methylpentanamide derivatives.

NITROGEN-CONTAINING HETEROCYCLIC AMIDE COMPOUND AND PHARMACEUTICAL USE THEREOF

PROBLEM TO BE SOLVED: To provide a nitrogen-containing heterocyclic amide compound having pyruvate dehydrogenase kinase inhibitory activity, or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition containing the same. SOLUTION: The present invention provides a compound of formula [I-a] or formula [II], or a pharmaceutically acceptable salt thereof (a bond of a dotted line: a single bond or a double bond. X1: C, N, O. X2: C, N. R1a: C1-4 alkyl, C1-4 alkyl carbonyl. R2: halogen, cyano, C1-4 alkyl. A1-A7: C, N, O. A8: C, N. R3, R4: H, C1-4 alkyl. Cy1: C4-6 cycloalkyl or the like. Cy2: C3-6 cycloalkyl or the like. m, t, w: 0, 1. n, r, v: 0, 1, 2.) SELECTED DRAWING: None COPYRIGHT: (C)2019,JPOandINPIT

Compounding method for LCZ696 midbody

The invention discloses a compounding method for a LCZ696 midbody. The compounding route is as follows: wherein R1 is Me, Et or i-Pr; X is Cl, Br or I; R2 is Ms, Ts or Tf. According to the compounding method for the LCZ696 midbody disclosed by the invention, the methylating difficulty is reduced, the midbody is configured and overturned through the consequent reaction, the proportion of the required configuration is greatly increased, the product yield, purity and use ratio are increased and the industrial large-scale production is benefited.

Anti-Beckwith stereoselectivity in amidyl radical cyclisations: Bu 3SnH-mediated 5-exo-trig acyl mode cyclisation of 2-substituted pent-4-enamide radicals

2-Substituted amidyl radicals derived from 8a-d and 9a-d undergo acyl mode 5-exo-trig cyclisation to give 3,5-trans pyrrolidinones 11a-d and 14a-d as the major products in low diastereoselectivity (de = 9-36%). The steric nature of the nitrogen substituent attached to the amidyl radical does not have a significant effect on selectivity. The stereochemical outcome is opposite to that expected based upon applying the Beckwith rule.

Substituted Piperidines that Increase P53 Activity and the Uses Thereof

In its many embodiments, the present invention discloses novel compounds, as inhibitors of HDM2 protein, methods for preparing such compounds, pharmaceutical compositions including one or more such compounds, methods of treatment, prevention, inhibition, of one or more diseases associated with the HDM2 protein or P53 using such compounds or pharmaceutical compositions.

VLA-4 INHIBITORS

The present invention relates to a compound represented by the following formula (I): (wherein, W represents WA-A1 -WB - (in which, WA is substituted or unsubstituted aryl, etc., A1 is -NR1-, single bond, -C(O)-, etc., and WB is substituted or unsubstituted arylene, etc.), R is single bond, -NH-, -OCH2-, alkenylene, etc., X is -C(O) -CH2-, etc., and M is, for example, the following formula: (in which, R11, R12 and R13 each independently represents hydrogen, hydroxyl, amino, halogen, etc., R14 is hydrogen or lower alkyl, Y represents -CH2-O-, etc., Z is substituted or unsubstituted arylene, etc., A2 is single bond, etc, and R10 is hydroxyl or lower alkoxy)), or salt thereof; and a medicament containing the same. This compound or salt thereof selectively inhibits binding of cell adhesion molecules to VAL-4 and exhibits high bioavailability so that it is useful as a preventive and/or remedy for inflammatory diseases, autoimmune diseases, metastasis, bronchial asthma, rhinostenosis, diabetes, and the like.

Pyroglutamic acid in drug synthesis, part 1: A method for the synthesis of enantiomerically pure 4-alkyl-4-arylpyroglutamic acids

Synthesis of the title compounds is described, starting from alkylation of the pyroglutaminol-acetal 4a[1] at the α-lactam position C-6 with methyl iodide. Subsequent addition of 2-cyclohexen-1-one led to diastereoselective formation of the 1,2-aldol addition product 7b/7c, which after dehydratization was aromatized with DDQ to yield the 6-methyl-6-phenyl derivative 7h, Acetal cleavage and Jones oxidation yielded 4,4-disubstituted, enantiomerically pure pyroglutamic acid 3b. X-ray analysis confirmed the assignment of the configuration of the newly created chiral centre.

Functionalised pyrrolidinones derived from (S)-pyroglutamic acid

The generation of the lactam enolate derived from bicyclic lactams 2a-c, prepared from (S)-pyroglutamic acid 1a, and subsequent reaction with a range of electrophiles, is reported. Exo-diastereoselectivity is generally favoured. The deprotection of some of these adducts to give functionalised hydroxymethylpyrrolidinones is readily achieved by simple hemiaminal ether cleavage under acidic conditions.

Asymmetric synthesis of calyculin C. 2. Synthesis of the C26-C37 fragment and model Wittig couplings

We report our synthesis of the C26-C37 fragment of serine/threonine protein phosphatase PP1 and PP2A inhibitor calyculin C (1). Outlined in this paper are synthetic approaches to the two components based on disconnection at the C33-N3 amide bond. We report the successful synthesis of the C33-C37 aza-sugar derived from D-lyxose which was coupled onto a C26-C32 aminooxazole originating from L-pyroglutamic acid. Elaboration of the resulting amide to a fully deprotected C26-C37 fragment of calyculin C completed our synthesis. This provided an appropriate phosphonium salt for use in a Wittig olefination for joining both halves of the natural product.