74572-03-5

Usage

Uses

Used in Pharmaceutical Industry:
(R)-3-Phenylmorpholine is used as a key intermediate in the synthetic preparation of phosphoinositide kinase inhibitors. These inhibitors are important for the development of drugs targeting various diseases, including cancer and neurological disorders, due to their role in regulating cellular signaling pathways.
Used in Organic Synthesis:
(R)-3-Phenylmorpholine serves as a valuable chiral building block for the synthesis of enantioselective compounds. Its unique R-configuration and structural features make it suitable for the preparation of a wide range of pharmaceuticals, agrochemicals, and other specialty chemicals that require specific stereochemistry for their biological activity and efficacy.

InChI:InChI=1/C10H13NO/c1-2-4-9(5-3-1)10-8-12-7-6-11-10/h1-5,10-11H,6-8H2/t10-/m0/s1

Upstream product

• 192815-71-7 (5R)-5-phenylmorpholin-3-one 
• 56613-80-0 D-2-phenylglycinol 
• 79-04-9 chloroacetyl chloride 
• 94193-77-8 (R)-N-(2-hydroxy-1-phenylethyl)-2-chloroacetamide 
• 529-20-4 2-methylphenyl aldehyde 
• 74571-97-4 (R)-2-[Benzyl-(2-hydroxy-ethyl)-amino]-2-phenyl-ethanol 
• 14231-57-3 (R)-N-benzyl-2-phenylglycinol 
• 74572-00-2 (3R)-4-benzyl-3-phenylmorpholine 
• 1436416-04-4 N-[3-formyl-6-((R)-3-phenylmorpholin-4-yl)-pyridin-2-yl]-2,2-dimethylpropionamide 

Downstream Products

• 74572-24-0 (R)-4-(1-Oxy-pyridin-2-yl)-3-phenyl-morpholine 
• 1052208-75-9 C₁₉H₂₂N₂O₂S 
• 1349830-14-3 (R)-6-(3-phenylmorpholino)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one 
• 1349830-25-6 (R)-6-(3-phenylmorpholino)-2H-benzo[b][1,4]oxazin-3(4H)-one 
• 1374765-94-2 3-(cyclopropylmethyl)-7-[[(3R)-3-phenyl-4-morpholinyl]methyl]-8-(trifluoromethyl)-1,2,4-triazolo[4,3-a]pyridine 
• 1429228-64-7 (R)-tert-butyl 3-phenylmorpholine-4-carboxylate 
• 1429228-65-8 (R)-tert-butyl 3-(4-iodophenyl)morpholine-4-carboxylate 
• 1429228-66-9 tert-butyl (3R)-3-(4-methoxycarbonylphenyl)morpholine-4-carboxylate 
• 1429228-67-0 tert-butyl (3R)-3-[4-(hydroxymethyl)phenyl]morpholine-4-carboxylate 
• 1429228-68-1 tert-butyl (3R)-3-(4-formylphenyl)morpholine-4-carboxylate 
• 1429228-69-2 tert-butyl (3R)-3-{4-[(hydroxyimino)methyl]phenyl}morpholine-4-carboxylate 
• 1429228-71-6 tert-butyl (3R)-3-{4-[5-(3-{bis[(tert-butoxy)carbonyl]amino}-6-[4-(propane-2-sulfonyl)phenyl]pyrazin-2-yl)-1,2-oxazol-3-yl]phenyl}morpholine-4-carboxylate 
• 1429228-63-6 5-(4-isopropylsulfonylphenyl)-3-[3-[4-[(3R)-morpholin-3-yl]phenyl]isoxazol-5-yl]pyrazin-2-amine 
• 1429228-72-7 tert-butyl (3R)-3-[4-[5-[3-[bis(tert-butoxycarbonyl)amino]-6-bromo-pyrazin-2-yl]isoxazol-3-yl]phenyl]morpholine-4-carboxylate 

Relevant academic research and scientific papers

Using the competing enantioselective conversion method to assign the absolute configuration of cyclic amines with BODE’s acylation reagents

The competing enantioselective conversion (CEC) method is a quick and reliable means to determine absolute configuration. Previously, Bode’s chiral acylated hydroxamic acids were used to determine the stereochemistry of primary amines, as well as cyclic and acyclic secondary amines. The enantioselective acylation has been evaluated for 4-, 5-, and 6-membered cyclic secondary amines, including medicinally relevant compounds. The limitations of the method were studied through computational analysis and experimental results. Piperidines with substituents at the 2-position did not behave well unless the axial conformer was energetically accessible, which is consistent with the transition state geometries proposed by Bode and Kozlowski. Control experiments were performed to investigate the cause of degrading selectivity under the CEC reaction conditions. The present study expands the scope of the CEC method for secondary amines and provides a better understanding of the reaction profile.

Formal Deoxygenative Hydrogenation of Lactams Using PNHP-Pincer Ruthenium Complexes under Nonacidic Conditions

A formal deoxygenative hydrogenation of amides to amines with RuCl2(NHC)(PNHP) (NHC = 1,3-dimethylimizadol-2-ylidene, PNHP = bis(2-diphenylphosphinoethyl)amine) is described. Various secondary amides, especially NH-lactams, are reduced with H2 (3.0-5.0 MPa) to amines at a temperature range of 120-150 °C with 1.0-2.0 mol % of PNHP-Ru catalysts in the presence of Cs2CO3. This process consists of (1) deaminative hydrogenation of secondary amides to generate primary amines and alcohols, (2) dehydrogenative coupling of the transient amines with alcohols to generate imines, and (3) hydrogenation of imines to give the formally deoxygenated secondary amine products.

SUBSTITUTED MORPHOLINE DERIVATIVES AS ROR GAMMA MODULATORS

The present disclosure is directed to compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein ring A, R1, R2, R3, X1, X2, m and n are as defined herein, which are active as modulators of retinoid-related orphan receptor gamma t (RORyt). These compounds prevent, inhibit, or suppress the action of RORyt and are therefore useful in the treatment of RORyt mediated diseases, disorders, syndromes or conditions such as, e.g., pain, inflammation, COPD, asthma, rheumatoid arthritis, colitis, multiple sclerosis, psoriasis, neurodegenerative diseases and cancer. (I)

Efficient Routes to a Diverse Array of Amino Alcohol-Derived Chiral Fragments

Efficient syntheses of chiral fragments derived from chiral amino alcohols are described. Several unique scaffolds were readily accessed in 1-5 synthetic steps leading to 45 chiral fragments, including oxazolidinones, morpholinones, lactams, and sultams. These fragments have molecular weights ranging from 100 to 255 Da and are soluble in water (0.085 to >15 mM).

Catalytic Synthesis of N-Unprotected Piperazines, Morpholines, and Thiomorpholines from Aldehydes and SnAP Reagents

Commercially available SnAP (stannyl amine protocol) reagents allow the transformation of aldehydes and ketones into a variety of N-unprotected heterocycles. By identifying new ligands and reaction conditions, a robust catalytic variant that expands the substrate scope to previously inaccessible heteroaromatic substrates and new substitution patterns was realized. It also establishes the basis for a catalytic enantioselective process through the use of chiral ligands. SnAPcat! The identification of new ligands and reaction conditions provides a robust catalytic method for the synthesis of N-unprotected heterocycles using SnAP reagents. This catalytic variant expands the substrate scope to include previously inaccessible piperazines, morpholines, and thiomorpholines and establishes the basis for a catalytic enantioselective process through the use of chiral ligands.

COMPOUNDS USEFUL AS INHIBITORS OF ATR KINASE

The invention relates to the compound 5-(4-isopropylsulfonylphenyl) -3-[3-[4-[(3R)-morpholin-3-yl]phenyl]isoxazol-5-yl]pyrazine-2-amine and pharmaceutically acceptable salts thereof. The compounds are useful as inhibitors of ATR kinase.

Synthesis of a cis 2,5-disubstituted morpholine by de-epimerization: Application to the multigram scale synthesis of a mineralocorticoid antagonist

A convergent route to multigram quantities of a mineralocorticoid antagonist 3 is described. Starting from (R)-phenylglycinol, the synthesis of cis 2,5-morpholine 2 is accomplished utilizing a de-epimerization to install the second stereogenic center. The multigram synthesis of 3 was completed through a sequence of an SNAr reaction, Dakin oxidation, alkylation, and cyclization to provide a crystalline solid.

4-(1,3-Thiazol-2-yl)morpholine derivatives as inhibitors of phosphoinositide 3-kinase

4-(1,3-Thiazol-2-yl)morpholine derivatives have been identified as potent and selective inhibitors of phosphoinositide 3-kinase. The SAR data of selected examples are presented and the in vivo profiling of compound 18 is shown to demonstrate the utility of this class of compounds in xenograft models of tumor growth.

SYNTHESIS AND ABSOLUTE CONFIGURATION OF SUBSTITUTED MORPHOLINES

We studied methods of stereospecific synthesis that enabled us to obtain variously substituted morpholinic compounds and to determine their absolute configuration.From a study of the chiroptical properties of synthetic N-(2-pyridyl-N-oxide) derivatives of optically active morpholines, it was possible to correlate the sign of the Cotton effect with the absolute configuration.This correlation agrees with that previously established for derivatives of the piperidine type.By evaluating the various contributions to the Cotton effect of substituents in positions 2 and 3, we established the absolute configuration of bicyclic compounds condensed in the two positions mentioned above.