937271-45-9

Usage

Uses

Used in Organic Synthesis:
4-(3-(but-3-en-1-yloxy)phenyl)-2-chloropyrimidine is used as a building block in organic synthesis for the creation of various complex organic molecules. Its unique structure allows for versatile chemical reactions and modifications, facilitating the synthesis of a wide range of compounds.
Used in Pharmaceutical Research:
In the pharmaceutical industry, 4-(3-(but-3-en-1-yloxy)phenyl)-2-chloropyrimidine is utilized as a key intermediate in the development of new drugs. Its unique chemical properties and potential biological activities make it a promising candidate for the discovery of novel therapeutic agents.
Used in Agrochemical Development:
4-(3-(but-3-en-1-yloxy)phenyl)-2-chloropyrimidine may also have potential applications in the development of new agrochemicals. Its unique structure and properties could contribute to the creation of innovative products for agriculture, such as pesticides or herbicides. However, further research is required to fully understand its potential uses and effects in this field.

Upstream product

• 5162-44-7 1-bromo-4-butene 
• 937271-43-7 3-(2-chloropyrimidine-4-yl)phenol 
• 87199-18-6 3-hydroxyphenylboronic acid 
• 3934-20-1 2,6-Dichloropyrimidine 

Downstream Products

• 1312603-49-8 (3-but-3-enyloxy-phenyl)-[4-(3-but-3-enyloxyphenyl)pyrimidin-2-yl]amine 
• 1312603-50-1 (3-allyloxymethyl-4-methoxyphenyl)-[4-(3-but-3-enyloxyphenyl)pyrimidin-2-yl]amine 
• 937273-28-4 (3-allyloxyphenyl)-[4-(3-but-3-enyloxyphenyl)pyrimidin-2-yl]amine 
• 1204918-72-8 TG02 
• 1354567-66-0 2-{2-[(allylmethylamino)methyl]-4-[4-(3-but-3-enyloxyphenyl)pyrimidin-2-ylamino]phenoxy}-1-pyrrolidin-1-ylethanone 
• 1354567-64-8 {3-[(allylmethylamino)methyl]-4-ethanesulfonylphenyl}-[4-(3-but-3-enyloxyphenyl)pyrimidin-2-yl]amine 
• 1354567-71-7 {allyl-[5-[4-(3-but-3-enyloxyphenyl)pyrimidin-2-ylamino]-2-(2-pyrrolidin-1-ylethoxy)benzyl]amino}acetonitrile 
• 1354567-70-6 [3-{[allyl-(2,2,2-trifluoroethyl)amino]methyl}-4-(2-pyrrolidin-1-ylethoxy)phenyl]-[4-(3-but-3-enyloxyphenyl)pyrimidin-2-yl]amine 
• 1354567-67-1 {3-[(allylmethylamino)methyl]-4-morpholin-4-ylphenyl}-[4-(3-but-3-enyloxyphenyl)pyrimidin-2-yl]amine 
• 1354567-76-2 N-{3-[(allylmethylamino)methyl]-5-[4-(3-but-3-enyloxyphenyl)pyrimidin-2-ylamino]phenyl}-2,2,2-trifluoroacetamide 
• 1354567-75-1 [3-[(allylmethylamino)methyl]-5-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]-[4-(3-but-3-enyloxyphenyl)pyrimidin-2-yl]amine 
• 1354567-74-0 [3-[(allylmethylamino)methyl]-4-(2-piperidin-1-ylethoxy)phenyl]-[4-(3-but-3-enyloxyphenyl)pyrimidin-2-yl]amine 
• 1354567-73-9 {3-[(allylmethylamino)methyl]-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-[4-(3-but-3-enyloxyphenyl)pyrimidin-2-yl]amine 
• 1354567-72-8 [3-[(allylmethylamino)methyl]-4-(2-morpholin-4-ylethoxy)phenyl]-[4-(3-but-3-enyloxyphenyl)pyrimidin-2-yl]amine 

Relevant academic research and scientific papers

Homogeneous and Functional Group Tolerant Ring-Closing Metathesis for DNA-Encoded Chemical Libraries

Reaction heterogeneity, poor pH control, and catalyst decomposition in the ring-closing metathesis (RCM) of DNA-chemical conjugates lead to poor yields of the cyclized products. Herein we address these issues with a RCM reaction system that includes a novel aqueous solvent combination to enable reaction homogeneity, an acidic buffer system which masks traditionally problematic functional groups, and a decomposition-resistant catalyst which maximizes conversion to the cyclized product. Additionally, we provide a systematic study of the substrate scope of the on-DNA RCM reaction, a demonstration of its applicability to a single-substrate DNA-encoded chemical library that includes sequencing analysis, and the first successful stapling of an unprotected on-DNA [i, i+4] peptide.

COVALENT INHIBITORS OF CDK-7

This disclosure includes compounds of Formula (I), wherein A, B, C, R1, R2, R3, R5, R6, m, n, W1, W2, Z1, Z2, Z3, Z4, L1, L2, and warhead are defined herein. Also disclosed is a method for treating a neoplastic disease with these compounds.

Solid state forms of macrocyclic kinase inhibitors

Provided herein are salt forms of macrocyclic protein kinase inhibitors, pharmaceutical compositions containing the same, methods of making and using these compounds and compositions to treat proliferative disease mediated by kinase activity.

Acid mediated ring closing metathesis: A powerful synthetic tool enabling the synthesis of clinical stage kinase inhibitors

The powerful olefin metathesis reaction was employed for the construction of late-phase clinical agents SB1317 and SB1518. In both cases RCM seems to proceed only in the presence of an acid and to predominantly furnish trans isomers. In case of SB1518 it proceeded in the presence of acid HCl, while for SB1317, it mainly proceeds in the presence of TFA (trifluroacetic acid).

Macrocyclic compounds as anti-cancer agents: Design and synthesis of multi-acting inhibitors against HDAC, FLT3 and JAK2

A novel series of macrocyclic compounds were designed and synthesized as multi-target inhibitors targeting HDAC, FLT3 and JAK2. Some of these compounds exhibited potent HDAC inhibition as well as FLT3 and JAK2 inhibition under both cell-free and cellular conditions. In vitro antiproliferative assay indicated that these compounds were interestingly more cytotoxic to MV4-11 cells bearing FLT3-ITD mutation and HEL cells bearing JAK2V617F mutation.

Discovery of kinase spectrum selective macrocycle (16E)-14-methyl-20-oxa-5, 7,14,26-tetraazatetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8(27) ,9,11,16,21,23-decaene (SB1317/TG02), a potent inhibitor of cyclin dependent kinases (CDKs), Janus kinase 2 (JAK2), and Fms-like tyrosine kinase-3 (FLT3) for the treatment of cancer

Herein, we describe the design, synthesis, and SAR of a series of unique small molecule macrocycles that show spectrum selective kinase inhibition of CDKs, JAK2, and FLT3. The most promising leads were assessed in vitro for their inhibition of cancer cell proliferation, solubility, CYP450 inhibition, and microsomal stability. This screening cascade revealed 26h as a preferred compound with target IC50 of 13, 73, and 56 nM for CDK2, JAK2 and FLT3, respectively. Pharmacokinetic (PK) studies of 26h in preclinical species showed good oral exposures. Oral efficacy was observed in colon (HCT-116) and lymphoma (Ramos) xenograft studies, in line with the observed PK/PD correlation. 26h (SB1317/TG02) was progressed into development in 2010 and is currently undergoing phase 1 clinical trials in advanced leukemias and multiple myeloma.

Discovery of the macrocycle 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7, 26-triaza-tetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27) ,16,21,23-decaene (SB1518), a potent Janus Kinase 2/Fms-like tyrosine kinase-3 (JAK2/FLT3) inhibitor for the treatment of myelofibrosis and lymphoma

Discovery of the activating mutation V617F in Janus Kinase 2 (JAK2 V617F), a tyrosine kinase critically involved in receptor signaling, recently ignited interest in JAK2 inhibitor therapy as a treatment for myelofibrosis (MF). Herein, we describe the design and synthesis of a series of small molecule 4-aryl-2-aminopyrimidine macrocycles and their biological evaluation against the JAK family of kinase enzymes and FLT3. The most promising leads were assessed for their in vitro ADME properties culminating in the discovery of 21c, a potent JAK2 (IC50 = 23 and 19 nM for JAK2 WT and JAK2V617F, respectively) and FLT3 (IC50 = 22 nM) inhibitor with selectivity against JAK1 and JAK3 (IC50 = 1280 and 520 nM, respectively). Further profiling of 21c in preclinical species and mouse xenograft and allograft models is described. Compound 21c (SB1518) was selected as a development candidate and progressed into clinical trials where it is currently in phase 2 for MF and lymphoma.

PYRIMIDINE DERIVATIVES

The present invention relates to pyrimidine compounds that are useful as agents for the treatment of kinase related disorders such as proliferative disorders. More particularly, the present invention relates to substituted pyrimidine compounds, methods for their preparation, pharmaceutical compositions containing these compounds and uses of these compounds in the treatment of proliferative disorders. These compounds may be useful as medicaments for the treatment of a number of kinase related disorders such as proliferative disorders including tumours and cancers as well as other disorders or conditions related to or associated with kinases.

OXYGEN LINKED PYRIMIDINE DERIVATIVES

The present invention relates to pyrimidine compounds that are useful as anti-proliferative agents. More particularly, the present invention relates to oxygen linked and substituted pyrimidine compounds, methods for their preparation, pharmaceutical compositions containing these compounds and uses of these compounds in the treatment of proliferative disorders. These compounds may be useful as medicaments for the treatment of a number of proliferative disorders including tumours and cancers as well as other disorders or conditions related to or associated with kinases.