863127-76-8

Usage

Uses

Used in Pharmaceutical Industry:
(E)-N-(2-Chloro-6-methylphenyl)-3-ethoxyacrylamide is used as a reagent for the preparation of potent and selective anti-tumor drugs, such as Dasatinib. It plays a crucial role in the synthesis of these drugs, contributing to their effectiveness in treating various types of cancer.
Dasatinib, a tyrosine kinase inhibitor, is known for its ability to target multiple oncogenic pathways, making it a valuable treatment option for patients with chronic myeloid leukemia and other malignancies. The use of (E)-N-(2-Chloro-6-methylphenyl)-3-ethoxyacrylamide in the production of Dasatinib highlights its importance in the development of life-saving medications.

InChI:InChI=1/C12H14ClNO2/c1-3-16-8-7-11(15)14-12-9(2)5-4-6-10(12)13/h4-8H,3H2,1-2H3,(H,14,15)/b8-7+

Synthetic route

(2E)-3-ethoxyprop-2-enoyl chloride (6191-99-7, 99471-66-6) + 2-chloro-6-methylaniline (87-63-8) → (E)-N-(2-chloro-6-methylphenyl)-3-ethoxyacrylamide (863127-76-8)

Conditions	Yield
With pyridine In tetrahydrofuran at 0 - 20℃; for 3h;	78.3%
With pyridine In tetrahydrofuran at 0 - 20℃; for 2h;	73.6%
With pyridine In tetrahydrofuran at 0 - 20℃;	73.6%
With pyridine In tetrahydrofuran at 10 - 30℃; for 4h;	300 g

3-ethoxyacryloyl chloride (6191-99-7) + 2-chloro-6-methylaniline (87-63-8) → (E)-N-(2-chloro-6-methylphenyl)-3-ethoxyacrylamide (863127-76-8)

Conditions	Yield
With pyridine In tetrahydrofuran at 20℃;
With pyridine In tetrahydrofuran at 20℃;

ethyl 3-ethoxyacrylate (1001-26-9) → (E)-N-(2-chloro-6-methylphenyl)-3-ethoxyacrylamide (863127-76-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium hydroxide; water / 2 h / Reflux 2: thionyl chloride / 2 h / Reflux 3: pyridine / tetrahydrofuran / 20 °C View Scheme

(E)-N-(2-chloro-6-methylphenyl)-3-ethoxyacrylamide (863127-76-8) + thiourea (17356-08-0) → 2-amino-N-(2-chloro-6-methylphenyl)-1,3-thiazole-5-carboxamide (302964-24-5)

Conditions	Yield
Stage #1: (E)-N-(2-chloro-6-methylphenyl)-3-ethoxyacrylamide With iodine(I) bromide; 1-n-butyl-3-methylimidazolim bromide In tetrahydrofuran at 40℃; Stage #2: thiourea In tetrahydrofuran for 1.5h; Temperature; Concentration; Solvent; Reagent/catalyst;	98.8%
Stage #1: (E)-N-(2-chloro-6-methylphenyl)-3-ethoxyacrylamide With N-Bromosuccinimide In 1,4-dioxane; water at -10 - 22℃; for 3h; Stage #2: thiourea In 1,4-dioxane; water at 100℃; for 2h; Stage #3: With ammonia In 1,4-dioxane; water at 20 - 22℃;	90%
Stage #1: (E)-N-(2-chloro-6-methylphenyl)-3-ethoxyacrylamide With N-Bromosuccinimide In 1,4-dioxane at -10 - 22℃; for 3h; Stage #2: thiourea In 1,4-dioxane at 100℃; for 2h; Stage #3: With ammonium hydroxide In 1,4-dioxane; water at 20 - 22℃;	90%
Stage #1: (E)-N-(2-chloro-6-methylphenyl)-3-ethoxyacrylamide With N-Bromosuccinimide In 1,4-dioxane; water at 25 - 30℃; for 3h; Stage #2: thiourea In 1,4-dioxane; water at 25 - 70℃; for 2h;	213 g

Upstream product

• 6191-99-7 (2E)-3-ethoxyprop-2-enoyl chloride 
• 87-63-8 2-chloro-6-methylaniline 
• 6191-99-7 3-ethoxyacryloyl chloride 
• 1001-26-9 ethyl 3-ethoxyacrylate 

Downstream Products

• 302964-24-5 2-amino-N-(2-chloro-6-methylphenyl)-1.3-thiazole-5-carboxamide 
• 1035343-44-2 C₁₅H₁₂Cl₂N₆OS 
• 1035343-45-3 C₂₁H₂₅ClN₈O₂S 
• 1035343-47-5 C₂₀H₂₃ClN₈OS 
• 1035343-70-4 C₂₂H₂₇ClN₈O₂S 
• 1258411-33-4 C₂₂H₂₉ClN₈OS 
• 1258411-04-9 C₂₅H₃₂ClN₉O₂S 
• 1258411-05-0 C₂₅H₂₆ClN₉OS 
• 1035343-57-7 C₂₁H₂₄ClN₇O₂S 
• 1258411-07-2 C₁₉H₂₁ClN₈OS 
• 1258411-08-3 C₂₂H₂₄ClN₉OS 
• 1258411-09-4 C₂₄H₂₄ClN₉OS 
• 1258411-10-7 C₂₃H₂₃ClN₁₀OS 
• 1258411-11-8 C₂₅H₂₅ClN₈OS 

Relevant academic research and scientific papers

CRYSTALLINE FORMS OF N-(2-CHLORO-6-METHY]PHENVN-2-[F6-[4-(2-HVDROXVETHVL)-L- PIPERAZINVIL-2-METHVL-4-PVRIMIDINVLLAMINOL-5-THIAZOLECARBOXAMIDE AND THEIR PROCESS THEREOF

The present invention relates to crystalline 1,2-Propanediol solvate of N-(2-chloro-6- methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-l-piperazinyl]-2-methyl-4-pyrimidinyl]ainino]-5- thiazolecarboxamide compound of formula- lb, its process for the preparation and its use in the preparation of anhydrous crystalline form (N-6) and monohydrate of N-(2-chloro-6- methy lphenyl)-2- [ [6- [4-(2 -hydroxy ethyl)- 1 -piperazinyl] -2-methyl-4-pyrimidinyl]amino] -5 - thiazolecarboxamide. [formula] 1,2-Propanediol solvate Formula- lb

Synthesis and biological activities of 2-amino-thiazole-5-carboxylic acid phenylamide derivatives

In an attempt to develop potent and selective anti-tumor drugs, a series of novel 2-amino-thiazole-5-carboxylic acid phenylamide derivatives were designed based on the structure of dasatinib. All compounds were synthesized by a systematic combinatorial chemical approach. Biological evaluation revealed that N-(2-chloro-6-methylphenyl)-2-(2-(4-methylpiperazin-1-yl)acetamido) thiazole-5-carboxamide (6d) exhibited high antiproliferative potency on human K563 leukemia cells comparable to dasatinib. Against mammary and colon carcinoma cells 6d was either inactive (MDA-MB 231) or distinctly less active (MCF-7 and HT-29: IC50=20.2 and 21.6μM, respectively). Dasatinib showed at each cell line IC501μM. The results of this structure activity relationship study clearly documented that the pyrimidin-4-ylamino core of dasatinib is responsible for the anti-tumor activity against non-leukemia cell lines.

TRIAZINE DERIVATIVES AND THEIR THERAPEUTICAL APPLICATIONS

The present invention comprises inter alia compounds as shown in formula (I) or a pharmaceutically acceptable salt thereof.

A new and efficient preparation of 2-aminothiazole-5-carbamides: Applications to the synthesis of the anti-cancer drug dasatinib

A new and efficient method has been developed for the synthesis of 2-amino-N-(-(2-chloro-6-methylphenyl)-thiazole-5-carboxamide. The new method involves a chemoselective α-bromination of β-ethoxyacrylamide followed by a one-pot treatment with thiourea to give the desired 2-aminothiazole-5-carboxylamide in excellent yield. Application of this new method to the efficient synthesis of the anti-cancer drug dasatinib was demonstrated.

TRIAZINE DERIVATIVES AND THEIR THERAPEUTICAL APPLICATIONS

The invention provides for Triazine derivatives and their use to modulate protein kinase activity in a variety of conditions and diseases.

PROCESS FOR PREPARING 2-AMINOTHIAZOLE-5-AROMATIC CARBOXAMIDES AS KINASE INHIBITORS

The invention relates to processes for preparing compounds having the formula (I) and crystalline forms thereof, wherein Ar is aryl or heteroaryl, L is an optional alkylene linker, and R2, R3, R4, and R5, are as defined in the specification herein, which compounds are useful as kinase inhibitors, in particular, inhibitors of protein tyrosine kinase and p38 kinase.