308348-93-8

Usage

Uses

Used in Pharmaceutical Industry:
METHYL 2-AMINOPYRIMIDINE-5-CARBOXYLATE is used as an intermediate in organic synthesis for the production of pharmaceuticals, contributing to the development of new drugs and improving existing ones.
Used in Agrochemical Industry:
In the agrochemical sector, METHYL 2-AMINOPYRIMIDINE-5-CARBOXYLATE is utilized as an intermediate in the synthesis of various agrochemicals, enhancing crop protection and yield.
Used in Fine Chemicals Industry:
METHYL 2-AMINOPYRIMIDINE-5-CARBOXYLATE is used as an intermediate for the production of other fine chemicals, broadening its applications in various chemical processes and products.
Used in Heterocyclic Compounds Preparation:
METHYL 2-AMINOPYRIMIDINE-5-CARBOXYLATE is used as a building block in the preparation of various heterocyclic compounds, which are important in the synthesis of complex organic molecules and have diverse applications in chemistry and biology.

Upstream product

• 50-01-1 guanidine hydrochloride 
• 80-62-6 methacrylic acid methyl ester 
• 506-93-4 guanidine nitrate 
• 7424-91-1 methyl 3,3-dimethoxypropionate 
• 107-31-3 Methyl formate 
• 67-56-1 methanol 
• 7752-82-1 5-bromo-2-aminopyrimidine 
• 201230-82-2 carbon monoxide 

Downstream Products

• 3167-50-8 2-amino-pyrimidine-5-carboxylic acid 
• 1001341-86-1 2-((4-(2-pyrrolidin-1-ylethoxy)phenyl)amino)pyrimidine-5-carboxylic acid 
• 1001341-90-7 2-((4-(2-pyrrolidin-1-ylethoxy)phenyl)amino)pyrimidine-5-carbonyl chloride 
• 1001341-93-0 2-((3-(2-pyrrolidin-1-ylethoxy)phenyl)amino)pyrimidine-5-carboxylic acid 
• 1581701-25-8 2-amino-N-(2-methyl-5-((4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)carbamoyl)phenyl)pyrimidine-5-carboxamide 
• 287714-35-6 2-chloro-pyrimidine-5-carboxylic acid methyl ester 
• 1083196-24-0 methyl imidazo[1,2-a]pyrimidin-6-carboxylate 
• 944896-64-4 imidazo [1,2-a]pyrimidine-6-carboxylic acid 
• 120747-84-4 2-aminopyrimidine-5-carboxyaldehyde 
• 1001341-91-8 methyl 2-((3-(2-pyrrolidin-1-ylethoxy)phenyl)amino)pyrimidine-5-carboxylate 
• 1001341-83-8 methyl 2-((4-(2-pyrrolidin-1-ylethoxy)phenyl)amino)pyrimidine-5-carboxylate 
• 1032568-63-0 copanlisib 
• 1339928-25-4 CUDC-907 

Relevant academic research and scientific papers

Synthesis method of copanlisib intermediate methyl 2-aminopyrimidine-5-carboxylate

The invention provides a synthetic method of a copanlisib intermediate methyl 2-aminopyrimidine-5-carboxylate, which comprises the following specific reaction steps: reacting sodium methoxide, ethyl formate and methyl 3,3-dimethoxypropionate in a methanol solvent at room temperature for 5 hours, then adding guanidine hydrochloride, conducting reacting at 50-55 DEG C for 2 hours, conducting cooling to room temperature after the reaction is completed, and conducting filtering and drying to obtain methyl 2-aminopyrimidine-5-carboxylate. The invention solves the problems of tedious reaction, high-risk raw material need, much waste liquid and waste water generated in the production process and the like in the existing reaction of the copanlisib intermediate methyl 2-aminopyrimidine-5-carboxylate, and provides a novel synthetic method of the copanlisib intermeidate methyl 2-aminopyrimidine-5-carboxylate, and the preparation method is simple, safe and controllable in reaction process, cheap and easily available in raw materials, high in yield, less in generated three wastes and the like.

Simple preparation method of 2-aminopyrimidine-5-formate

The invention provides a simple preparation method of 2-aminopyrimidine-5-formate. The preparation method comprises: carrying out a substitution reaction on 2-methacrylate as a raw material and a halogenating reagent 1, carrying out an addition reaction with a halogenating reagent 2 to obtain 2,3,3-trihalogenated-2-halogenated methyl propionate, and condensing the obtained 2,3,3-trihalogenated-2-halogenated methyl propionate and a guanidine salt to prepare 2-aminopyrimidine-5-formate. According to the invention, the raw materials used in the method are cheap, easy to obtain and low in cost; and the preparation method has characteristics of simpleness, easily achieved conditions, good operation safety, little wastewater generation, environmental protection, high target product yield and high target product purity, and is suitable for industrial production.

COMBINATION THERAPY WITH A PHOSPHOINOSITIDE 3-KINASE INHIBITOR WITH A ZINC BINDING MOIETY

The invention provides a method of treating cancer in a subject in need thereof, comprising administering to the subject: (a) a compound of Formula I: or a pharmaceutically acceptable salt thereof, wherein R is hydrogen or an acyl group; and (b) a PD-1 signaling inhibitor; wherein the compound of Formula I or pharmaceutically acceptable salt thereof and the PD-1 signaling inhibitor are administered in amounts which in combination are therapeutically effective. The invention further provides a pharmaceutical composition comprising a compound of Formula I or a pharmaceutically acceptable salt thereof, a PD-1 signaling inhibitor and a pharmaceutically acceptable carrier or excipient.

COMBINATION THERAPY WITH A PHOSPHOINOSITIDE 3-KINASE INHIBITOR WITH A ZINC BINDING MOIETY

The invention provides a method of treating cancer in a subject in need thereof, comprising administering to the subject: (a) a compound of Formula I: or a pharmaceutically acceptable salt thereof, wherein R is hydrogen or an acyl group; and (b) a BCL-2 inhibitor; wherein the compound of Formula I or pharmaceutically acceptable salt thereof and a BCL-2 inhibitor are administered in amounts which in combination are therapeutically effective. The invention further provides a pharmaceutical composition comprising a compound of Formula I or a pharmaceutically acceptable salt thereof, a BCL-2 inhibitor and a pharmaceutically acceptable carrier or excipient.

New tetrahydropyrido pyrimidinecarboxylic compound or salt thereof

To provide a compound having an inhibitory activity for an androgen receptor. A tetrahydropyridopyrimidine compound represented by the following general formula (I) or a pharmaceutically acceptable thereof (in the formula, X and R are as defined in the specification).

Phosphoinositide 3-kinase inhibitor with a zinc binding moiety

The invention provides a compound of Formula I, Pharmaceutical compositions comprising such compounds and the use of such compounds in the treatment of phosphoinositide 3-kinase related diseases and disorders such as cancer. The instant application further relates to the treatment of histone deacetylase related disorders and diseases related to both histone deacetylase and phosphoinositide 3-kinase.

Discovery and SAR of Novel 2,3-Dihydroimidazo[1,2-c]quinazoline PI3K Inhibitors: Identification of Copanlisib (BAY 80-6946)

The phosphoinositide 3-kinase (PI3K) pathway is aberrantly activated in many disease states, including tumor cells, either by growth factor receptor tyrosine kinases or by the genetic mutation and amplification of key pathway components. A variety of PI3K isoforms play differential roles in cancers. As such, the development of PI3K inhibitors from novel compound classes should lead to differential pharmacological and pharmacokinetic profiles and allow exploration in various indications, combinations, and dosing regimens. A screening effort aimed at the identification of PI3Kγ inhibitors for the treatment of inflammatory diseases led to the discovery of the novel 2,3-dihydroimidazo[1,2-c]quinazoline class of PI3K inhibitors. A subsequent lead optimization program targeting cancer therapy focused on inhibition of PI3Kα and PI3Kβ. Herein, initial structure–activity relationship findings for this class and the optimization that led to the identification of copanlisib (BAY 80-6946) as a clinical candidate for the treatment of solid and hematological tumors are described.

Identification and optimization of new dual inhibitors of B-Raf and epidermal growth factor receptor kinases for overcoming resistance against vemurafenib

Epidermal growth factor receptor (EGFR) amplification has been demonstrated to be critical for the inherent and/or acquired resistance against current B-RafV600E inhibitor therapy for melanoma and colorectal cancer patients. We describe the discovery and structure-activity relationship study of a series of 1H-pyrazolo[3,4-b]pyridine-5-carboxamide analogues as novel dual inhibitors of EGFR and B-RafV600E mutant. One of the most promising compounds, 6a, potently inhibited both of the kinases with IC50 values of 8.0 and 51 nM, respectively. The compound also strongly suppressed the proliferation of a panel of intrinsic and acquired resistant melanoma and/or colorectal cancer cells harboring overexpressed EGFR with submicromolar IC 50 values. Further mechanism investigation revealed that 6a could sustainably inhibit the activation of the MAPK path way in the resistant SK-MEL-28 PR30 melanoma cancer cells and WiDr colorectal cancer cells with EGFR amplification. Our results support the hypothesis that the EGFR/B-Raf V600E dual inhibition might be a tractable strategy to overcome the intrinsic and acquired resistance of melanoma and/or colorectal cancers against the current B-RafV600E inhibitor therapy.

HEDGEHOG ANTAGONISTS HAVING ZINC BINDING MOIETIES

The present invention provides compounds which antagonize hedgehog signaling and inhibit HDAC activity. The com-pounds can be used in methods of treating proliferative dis-eases and disorders such as cancer

AMIDO-BENZYL SULFONE AND SULFOXIDE DERIVATIVES

The present invention relates to certain amido-benzyl sulfoxide and sulfone compounds, pharmaceutical compositions comprising such compounds, and methods of treatment using such compounds.