917392-54-2

Usage

Uses

Used in Pharmaceutical Synthesis:
4-Methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]benzoic acid methyl ester is used as an intermediate in the synthesis of 4-Methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]benzamide (M326838). 4-Methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]benzoic acid methyl ester is an impurity of Nilotinib (N465300), which is a potential agent for the treatment of chronic myelogenous leukemia.
In the pharmaceutical industry, the synthesis of complex organic compounds often requires the use of intermediates to facilitate the production process. 4-Methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]benzoic acid methyl ester plays a crucial role in the synthesis of Nilotinib, a drug that has shown promise in treating chronic myelogenous leukemia. By using this intermediate, chemists can more efficiently produce the desired active pharmaceutical ingredient, potentially leading to more effective treatments for patients suffering from this disease.

InChI:InChI=1/C18H16N4O2/c1-12-5-6-13(17(23)24-2)10-16(12)22-18-20-9-7-15(21-18)14-4-3-8-19-11-14/h3-11H,1-2H3,(H,20,21,22)

Upstream product

• 1025716-98-6 3-guanidino-4-methylbenzoic acid methyl ester 
• 55314-16-4 3-(N,N-dimethylamino)-1-(pyridin-3-yl)prop-2-en-1-one 
• 350-03-8 methyl-3-pyridylketone 
• 104901-43-1 methyl 3-bromo-4-methylbenzoate 
• 66521-66-2 4-pyridin-3-ylpyrimidin-2-ylamine 
• 1692-25-7 3-pyridylboronic acid 
• 18595-18-1 3-amino-4-methyl benzoic acid methyl ester 
• 483324-01-2 2-chloro-4-(pyridin-3-yl)pyrimidine 
• 67-56-1 methanol 
• 641569-94-0 4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]amino}benzoic acid 
• 90347-66-3 methyl 3-iodo-4-methylbenzoate 
• 1025716-99-7 3-[(aminoiminomethyl)amino]-4-methylbenzoic acid methylester mononitrate 
• 55314-16-4 (E)-3-(dimethylamino)-1-(pyridin-3-yl)prop-2-en-1-one 

Downstream Products

• 641571-10-0 nilotinib 
• 641569-94-0 4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]amino}benzoic acid 
• 1205540-16-4 N-(3-bromo-5-(trifluoromethyl)phenyl)-4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)benzamide 
• 1186619-20-4 4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]benzoic acid N'-4-[[(4-methyl-1-piperazinyl)methyl]benzoyl]hydrazide 
• 1186619-25-9 4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]benzoic acid N'-[3,5-bis(trifluoromethyl)benzoyl]hydrazide 
• 1186620-26-7 4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]benzoic acid N'-(3-trifluoromethyl-4-methylbenzoyl)hydrazide 
• 1186619-38-4 4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]benzoic acid N'-(pyridin-3-carbonyl)hydrazide 
• 1079904-27-0 [2-methyl-5-(6-trifluoromethyl-1H-benzoimidazol-2-yl)-phenyl]-(4-pyridin-3-yl-pyrimidin-2-yl)-amine 
• 1079911-30-0 {5-[5-(3-difluoromethoxy-phenyl)-2H-[1,2,4]triazol-3-yl]-2-methyl-phenyl}-(4-pyridin-3-yl-pyrimidin-2-yl)-amine 

Relevant academic research and scientific papers

SYNTHESIS OF 6-METHYL-N1-(4-(PYRIDIN-3-YL)PYRIMIDIN-2-YL)BENZENE-1,3-DIAMINE

Processes and useful intermediates for the synthesis of the tyrosine kinase inhibitors Formula (II) nilotinib and Formula (IV) imatinib. Key intermediates, method for their synthesis and their use in a divergent synthesis, making use of a Curtius rearrangement, to nilotinib and imatinib are described.

MANUFACTURING METHOD OF BENZOIC ACID COMPOUND

PROBLEM TO BE SOLVED: To provide a simple and high yield manufacturing method of 3-[(aminoiminomethyl)amino]-4-methylbenzoic acid (C1 to C4 alkyl)ester sulfate and ester thereof. SOLUTION: There is provided a method for manufacturing 3-[(aminoiminomethyl)amino]-4-methylbenzoic acid (C1 to C4 alkyl)ester sulfate (sulfate of the formula 2) from 3-amino-4-methylbenzoic acid (C1 to C4 alkyl)ester and cyanamide. In the formula R1 represents a C1 to C4 alkyl group. Further there is provided a simple and high yield 4-methyl-3-{[4-(pyridine-3-yl)pyrimidine-2-yl]amino}-benzoic acid which is a manufacturing intermediate of nilotinib using the compound. SELECTED DRAWING: None COPYRIGHT: (C)2020,JPOandINPIT

DEUTERATED AMINOPYRIDINE COMPOUNDS

The present disclosure is directed to Compound I and Compound II as well as pharmaceutical compositions including Compound I or Compound II, or mixtures thereof. The disclosure is additionally directed to methods of making the aforementioned compounds and

Syntheses and biological evaluation of 1,2,3-triazole and 1,3,4-oxadiazole derivatives of imatinib

Three novel series of 1,2,3-triazole and 1,3,4-oxadiazole derivatives of imatinib were prepared and evaluated in vitro for their cytostatic effects against a human chronic myeloid leukemia (K562), acute myeloid leukemia (HL60), and human leukemia stem-like cell line (KG1a). The structure-activity relationship was analyzed by determining the inhibitory rate of each imatinib analog. Benzene and piperazine rings were necessary groups in these compounds for maintaining inhibitory activities against the K562 and HL60 cell lines. Introducing a trifluoromethyl group significantly enhanced the potency of the compounds against these two cell lines. Surprisingly, some compounds showed significant inhibitory activities against KG1a cells without inhibiting common leukemia cell lines (K562 and HL60). These findings suggest that these compounds are able to inhibit leukemia stem-like cells.

Completely N1-selective palladium-catalyzed arylation of unsymmetric imidazoles: Application to the synthesis of nilotinib

The completely N1-selective Pd-catalyzed arylation of unsymmetric imidazoles with aryl halides and triflates is described. This study showed that imidazoles have a strong inhibitory effect on the in situ formation of the catalytically active Pd(0)-ligand complex. The efficacy of the N-arylation reaction was improved drastically by the use of a preactivated solution of Pd2(dba)3 and L1. From these findings, it is clear that while imidazoles can prevent binding of L1 to Pd, once the ligand is bound to the metal, these heterocycles do not displace it. The utility of the present catalytic system was demonstrated by the regioselective synthesis of the clinically important tyrosine kinase inhibitor nilotinib.

Rapid synthesis of Abelson tyrosine kinase inhibitors using click chemistry

Protein kinases catalyze the phosphorylation of serine, threonine, tyrosine and histidine residues in proteins. Aberrant regulation of kinase activity has been implicated in many diseases including cancer. Thus development of new strategies for kinase inhibitor design remains an active area of research with direct relevance to drug development. Abelson (Abl) tyrosine kinase is one of the Src-family of tyrosine kinases and is directly implicated in Chronic Myelogenous Leukemia (CML). In this article, we have, for the first time, developed an efficient method for the construction of small molecule-based bisubstrate inhibitors of Abl kinase using click chemistry. Subsequent biochemical screenings revealed a set of moderately potent inhibitors, a few of which have comparable potency to Imatinib (an FDA-approved drug for treatment of chronic myeloid leukemia) against Abl.

HETEROCYCLIC COMPOUNDS AND USES THEREOF

The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.

COMPOUNDS AND COMPOSITIONS AS C-KIT AND PDGFR KINASE INHIBITORS

The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated kinase activity, particularly diseases or disorders that involve abnormal activation of c-kit, PDGFR alpha and PDGFR beta kinases

PYRIMIDINE DERIVATIVES AND COMPOSITIONS AS C-KIT AND PDGFR KINASE INHIBITORS

The invention provides a novel class of pyrimidine derivatives, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated kinase activity, particularly diseases or disorders that involve abnormal activation of c-kit, PDGFRα and PDGFRβ kinases.

COMPOUNDS AND COMPOSITIONS AS PROTEIN KINASE INHIBITORS

The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to beat or prevent diseases or disorders associated with abnormal or deregulated kinase activity, particularly diseases or disorders that involve abnormal activation of c-kit, PDGFRα and PDGFRβ kinases. Formula (I).