955979-02-9

Basic information

• Product Name: 2-chloro-7-Methyl-4-Morpholinothieno[3,2-d]pyriMidine-6-carbaldehyde
• Synonyms: 2-chloro-7-Methyl-4-Morpholinothieno[3,2-d]pyriMidine-6-carbaldehyde;Thieno[3,2-d]pyriMidine-6-carboxaldehyde, 2-chloro-7-Methyl-4-(4-Morpholinyl)-;2-chloro-7-Methyl-4-Morpholinothieno[3,2-d]pyriMidine-6-carbaldehyde-5
• CAS NO: 955979-02-9
• Molecular Formula: C12H12ClN3O2S
• Molecular Weight: 297.76058
• Mol File: 955979-02-9.mol
• Article Data: 7

Chemical Properties

• Appearance: /
• CAS DataBase Reference: 2-chloro-7-Methyl-4-Morpholinothieno[3,2-d]pyriMidine-6-carbaldehyde(CAS DataBase Reference)
• NIST Chemistry Reference: 2-chloro-7-Methyl-4-Morpholinothieno[3,2-d]pyriMidine-6-carbaldehyde(955979-02-9)
• EPA Substance Registry System: 2-chloro-7-Methyl-4-Morpholinothieno[3,2-d]pyriMidine-6-carbaldehyde(955979-02-9)

Safety Data

• Hazardous Substances Data: 955979-02-9(Hazardous Substances Data)

Usage

General Description

2-chloro-7-Methyl-4-Morpholinothieno[3,2-d]pyriMidine-6-carbaldehyde is a chemical compound with a complex structure composed of various functional groups. It contains a chloro group, a methyl group, a morpholine ring, and a thieno[3,2-d]pyridine ring, as well as an aldehyde group. 2-chloro-7-Methyl-4-Morpholinothieno[3,2-d]pyriMidine-6-carbaldehyde has potential applications in the field of pharmaceuticals, as it may exhibit biological activity and could be used as a building block for the synthesis of other organic molecules. Its specific properties and potential uses would need to be further studied and characterized in order to fully understand its potential applications.

Upstream product

• 35265-83-9 2,4-dichloro-7-methyl-thieno[3,2-d]pyrimidine 
• 35265-81-7 7-methylthieno<3,2-d>pyrimidine-2,4-dione 
• 85006-31-1 3-amino-4-methyl-2-thiophenecarboxylic acid methyl ester 
• 35265-88-4 4-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)morpholine 
• 68-12-2 N,N-dimethyl-formamide 

Downstream Products

• 1032757-09-7 (R)-1-(4-((2-(2-aminopyrimidin-5-yl)-7-methyl-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)-2-hydroxypropan-1-one 

Relevant articles and documents

PARP-1/PI3K double-target inhibitor or pharmaceutically acceptable salt thereof, preparation method and application thereof

The invention discloses a PARP-1/PI3K double-target inhibitor or a pharmaceutically acceptable salt thereof, a preparation method and application thereof. According to the invention, the single active component can play a dual inhibition role on PARP-1 and PI3K, so that the dosage is reduced, the treatment effect is improved, and the toxic and side effects are reduced; and the dual inhibition effect on PARP-1 and PI3K is significant, the IC50 value of each target does not exceed 1.0 [mu]M, and the drug using the PARP-1/PI3K double-target inhibitor as the active component can be used for treating a variety of cancers or tumors related to PARP-1 and/or PI3K.

A practical, protecting-group-free synthesis of a PI3K/mTOR inhibitor

We report a practical and protecting-group-free synthesis amenable to produce multikilogram amounts of PI3K/mTOR inhibitor GDC-0980. The route employed metalation/formylation and reductive amination followed by a metal catalyzed Suzuki-Miyaura cross-coupling. The metalation was performed via triarylmagnesiate intermediates allowing formylation under noncryogenic conditions. 2-Picoline·BH3 was employed to replace Na(OAc)3BH in the reductive amination and to eliminate the use of molecular sieves. A concise one-step synthesis was developed for the selective monoamidation of piperazine with (S)-lactate to produce the piperazine lactamide starting material. The boronic acid was produced from 2-amino-5-bromopyrimidine in a one-step and protecting-group-free approach. The final crystallization in 1-propanol and water afforded the API in 59% overall yield in four steps and >99% purity by HPLC.

Discovery of a potent, selective, and orally available class i phosphatidylinositol 3-kinase (PI3K)/Mammalian target of rapamycin (mTOR) kinase inhibitor (GDC-0980) for the treatment of cancer

The discovery of 2 (GDC-0980), a class I PI3K and mTOR kinase inhibitor for oncology indications, is described. mTOR inhibition was added to the class I PI3K inhibitor 1 (GDC-0941) scaffold primarily through the substitution of the indazole in 1 for a 2-aminopyrimidine. This substitution also increased the microsomal stability and the free fraction of compounds as evidenced through a pairwise comparison of molecules that were otherwise identical. Highlighted in detail are analogues of an advanced compound 4 that were designed to improve solubility, resulting in 2. This compound, is potent across PI3K class I isoforms with IC50s of 5, 27, 7, and 14 nM for PI3Kα, β, δ, and γ, respectively, inhibits mTOR with a Ki of 17 nM yet is highly selective versus a large panel of kinases including others in the PIKK family. On the basis of the cell potency, low clearance in mouse, and high free fraction, 2 demonstrated significant efficacy in mouse xenografts when dosed as low as 1 mg/kg orally and is currently in phase I clinical trials for cancer.