52127-83-0

Basic information

• Product Name: 4-(2,6-DICHLOROPYRIMIDIN-4-YL)MORPHOLINE
• Synonyms: 4-(2,6-DICHLOROPYRIMIDIN-4-YL)MORPHOLINE;4-(2,6-Dichloro-4-pyriMidyl)Morpholine;4-(2,6-Dichloropyrimidin-4-yl)
• CAS NO: 52127-83-0
• Molecular Formula: C₈H₉Cl₂N₃O
• Molecular Weight: 234.0826
• Mol File: 52127-83-0.mol

Chemical Properties

• Boiling Point: 396.137 °C at 760 mmHg
• Flash Point: 193.377 °C
• Appearance: /
• Density: 1.435 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.577
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility: Dichloromethane, Ethyl Acetate
• PKA: 0.03±0.39(Predicted)
• CAS DataBase Reference: 4-(2,6-DICHLOROPYRIMIDIN-4-YL)MORPHOLINE(CAS DataBase Reference)
• NIST Chemistry Reference: 4-(2,6-DICHLOROPYRIMIDIN-4-YL)MORPHOLINE(52127-83-0)
• EPA Substance Registry System: 4-(2,6-DICHLOROPYRIMIDIN-4-YL)MORPHOLINE(52127-83-0)

Safety Data

• Hazard Codes: T
• Statements: 25
• Safety Statements: 45
• Hazardous Substances Data: 52127-83-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
4-(2,6-Dichloropyrimidin-4-yl)morpholine is used as a reactant for the preparation of α-azinylalkylamino-substituted pyrimidines, which are known as JAK2 inhibitors. These inhibitors play a crucial role in the development of targeted therapies for various diseases, including autoimmune disorders and certain types of cancer. 4-(2,6-Dichloropyrimidin-4-yl)morpholine's ability to form JAK2 inhibitors makes it a valuable asset in the pharmaceutical industry, contributing to the advancement of novel treatments and improving patient outcomes.
Chemical Properties:
As a white solid, 4-(2,6-Dichloropyrimidin-4-yl)morpholine exhibits distinct chemical properties that make it suitable for use in the synthesis of JAK2 inhibitors. Its structural features, including the dichloro-pyrimidinyl group and the morpholine ring, contribute to its reactivity and compatibility with other chemical compounds in the synthesis process. These properties are essential for the development of effective and targeted therapeutic agents.

InChI:InChI=1/C8H9Cl2N3O/c9-6-5-7(12-8(10)11-6)13-1-3-14-4-2-13/h5H,1-4H2

Upstream product

• 110-91-8 morpholine 
• 3764-01-0 2,4,6-trichloropyrimidine 

Downstream Products

• 873566-62-2 4-chloro-2-(3-hydroxymethylphenyl)-6-morpholinopyrimidine 
• 873566-68-8 4-chloro-2-(3-hydroxyphenyl)-6-morpholinopyrimidine 
• 544693-01-8 4-(6-chloro-2-(2-(pyridin-2-yl)ethoxy)pyrimidin-4-yl)morpholine 
• 887402-10-0 6-[2-(pyridin-2-yl)-ethoxy]-2-chloro-4-(morpholin-4-yl)-pyrimidine 
• 887402-09-7 4-[2-(pyridin-2-yl)-ethoxy]-6-chloro-2-(morpholin-4-yl)-pyrimidine 
• 541550-50-9 2-chloro-4-[3-(3,4-dimethoxyphenyl)propyl]-6-morpholinopyrimidine 
• 541550-49-6 4-chloro-2-[3-(3,4-dimethoxyphenyl)propyl]-6-morpholinopyrimidine 
• 719285-83-3 4-(6-hydrazinyl-2-(2-(pyridin-2-yl)ethoxy)pyrimidin-4-yl)morpholine 
• 1013403-79-6 4-(4-aminophenyl)-2-(2-difluoromethylbenzimidazol-1-yl)-6-morpholinopyrimidine 
• 1013403-35-4 2-(2-difluoromethylbenzimidazol-1-yl)-4-(3-hydroxymethylphenyl)-6-morpholinopyrimidine 
• 1013403-80-9 4-(4-amino-3-fluorophenyl)-2-(2-difluoromethylbenzimidazol-1-yl)-6-morpholinopyrimidine 
• 1013403-37-6 4-(4-carboxyphenyl)-2-(2-difluoromethylbenzimidazol-1-yl)-6-morpholinopyrimidine 
• 1013403-75-2 2-(2-difluoromethylbenzimidazol-1-yl)-6-morpholino-4-[4-(4-methylpiperazin-1-yl)phenyl]pyrimidine 
• 1013403-40-1 2-(2-difluoromethylbenzimidazol-1-yl)-6-morpholino-4-(4-sarcosylaminophenyl)pyrimidine 

Relevant articles and documents

An efficient synthesis of designed 4-thiazolidinone fused pyrimidine derivatives as potent antimicrobial agents

A novel series of hybrid 2-substituted ((pyrimidin-2-yl)hydrazinyl)thiazolidin-4-one derivatives were synthesized by means of aromatic nucleophilic displacement of chlorine atoms of 2,4,6-trichloro pyrimidine. Synthesis of some novel 2-(2-(6-morpholino-4-substituted(phenyl amino)pyrimidin-2-yl)hydrazinyl)thiazol-4(5H)-one derivatives have been carried out by the displacement of chlorine atoms on the basis of functionality concept on varying conditions. The synthesized hydrazinyl thiazolidin-4-one pyrimidine derivatives were evaluated for their expected antimicrobialactivity; where, the majority of these compounds showed potent antibacterial and antifungal activities against the tested strains of bacteria and fungi. Afforded title analogs were subsequently characterized by elemental analysis, IR, 1H NMR, 13C NMR, Mass spectroscopy. SAR and HOMO-LUMO studies were also carried out for confirming the structure biological activity. Thus, these studies suggested that hydrazinyl pyrimidine derivatives bearing thiazolidinone moiety are interesting scaffolds for the development of novel antimicrobial agents.

Discovery of novel Jak2-Stat pathway inhibitors with extended residence time on target

The discovery of the activating mutation V617F in the JH2 domain of Jak2 and the modulation of oncogenic Stat3 by Jak2 inhibitors have spurred a great interest in the inhibition of the Jak2/Stat pathway in oncology. In this Letter, we communicate the discovery of novel inhibitors of the Jak2/Stat5 axis, the N-(1H-pyrazol-3-yl)pyrimidin-2-amino derivatives. The rationale, synthesis and biological evaluation of these derivatives are reported. Two lead analogs from this series, 6 and 9, displayed prolonged residence time on Jak2, at enzymatic level. Although 6 and 9 exhibited moderate selectivity in a selected kinase panel, we chose to test these inhibitors in vivo as a consequence to their long residence time. However, extended inhibition of Jak2 due to the long residence time, in the form of inhibiting phosphorylation of downstream Stat5, was not recapitulated in an in vivo setting.

PIKFYVE KINASE INHIBITORS

The present invention relates to compounds useful as inhibitors of phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) as well as their use for treating diseases and disorders associated with PIKfyve.

Pyrimidine terminal anchor polymerase 2 inhibitor as well as preparation method and application thereof

The invention belongs to the technical field of pharmaceutical chemistry, and particularly relates to a pyrimidine terminal anchor polymerase 2 inhibitor and a preparation method and application thereof. Compared with the prior art, the preparation method

INHIBITORS OF RAF KINASES

Provided herein are inhibitors of receptor tyrosine kinase effector, RAF, pharmaceutical compositions comprising said compounds, and methods for using said compounds for the treatment of diseases.

PIKFYVE INHIBITORS

The present application provides, inter alia, a compound of Formula (I) or a pharmaceutically acceptable salt thereof, wherein Y, Ar, X1, X2, X3, R1, R2, R3, R4, R5, a

PI3Kalpha/mTOR bikinase inhibitor as well as pharmaceutical composition and application thereof

The invention discloses a PI3Kalpha/mTOR bikinase inhibitor as well as a pharmaceutical composition and application thereof. The PI3Kalpha/mTOR bikinase inhibitor is prepared from a compound shown ina general formula (I), or a stereoisomer, a geometric isomeride, a hydrate, a solvate, or pharmaceutically acceptable salt or a prodrug: (the formula (1) is shown in the description.) The invention provides the PI3Kalpha/mTOR bikinase inhibitor and the pharmaceutical composition thereof for inhibiting PI3Kalpha/mTOR bikinase and proliferation diseases having a PI3Kalpha/mTOR bikinase effect; moreover, a more effective and higher selectivity inhibitor can be provided for treating the proliferation diseases having the PI3Kalpha/mTOR bikinase effect.

Synthesis and PI3 kinase inhibition activity of some novel trisubstituted morpholinopyrimidines

A number of new substituted morpholinopyrimidines were prepared utilizing sequential nucleophilic aromatic substitution and cross-coupling reactions. One of the disubstituted pyrimidines was converted into two trisubstituted compounds which were screened as PI3K inhibitors relative to the well-characterized PI3K inhibitor ZSTK474, and were found to be 1.5–3-times more potent. A leucine linker was attached to the most active inhibitor since it would remain on any peptide-containing prodrug after cleavage by prostate-specific antigen, and it did not prevent inhibition of AKT phosphorylation and hence the inhibition of PI3K by the modified inhibitor.

POTASSIUM CHANNEL MODULATORS

Provided are novel compounds of Formula (I): and pharmaceutically acceptable salts thereof, which are useful for treating a variety of diseases, disorders or conditions, associated with potassium channels. Also provided are pharmaceutical compositions comprising the novel compounds of Formula (I), pharmaceutically acceptable salts thereof, and methods for their use in treating one or more diseases, disorders or conditions, associated with potassium channels.

TREATMENT OF SKIN LESIONS

The present invention is relates to a compound of formula (I), wherein X1, X2 and X3 are, independently of each other, N or CH; with the proviso that at least two of X1 X2 and X3 are N; Y is N or CH; W is H or F; with the proviso that when W is F, then X1, X2 and X3 are N; R1 and R2 are independently of each other (i) a morpholinyl of formula (II) wherein the arrow denotes the bond in formula (I); and wherein R3 and R4 are independently of each other H, C1-C3alkyl optionally substituted with one or two OH, C1-C2fluoroalkyl, C1-C2alkoxy, C1alkoxyC1-C3alkyl, CN, or C(O)O-C1-C2alkyl; or R3 and R4 form together a bivalent residue -R5R6- selected from C1-C3alkylene optionally substituted with 1 to 4 F, -CH2-O-CH2-, -CH2-NH-CH2-, or any of the structures wherein the arrows denote the bonds in formula (II); or (ii) a saturated 6-membered heterocyclic ring Z selected from thiomorpholinyl and piperazinyl, optionally substituted by 1 to 3 R7; wherein R7 is independently at each occurrence C1-C3alkyl optionally substituted with one or two OH, C1-C2fluoroalkyl, C1-C2alkoxyC1-C3alkyl, C3-C6cycloalkyl; or two R7 substituents form together a bivalent residue-R8R9- selected from Ci-C3alkylene optionally substituted with 1 to 4 F, -CH2-O-CH2- or -O-CH2CH2-O-; with the proviso that at least one of R1 and R2is a morpholinyl of formula II; and prodrugs, metabolites, tautomers, solvates and pharmaceutically acceptable salts thereof, for use in the prevention or treatment of a skin lesion in a subject.