Tag: 100-200

The author of 《Process Development and Scale Up of a Selective JAK3 Covalent Inhibitor PF-06651600》 were Tao, Yong; McWilliams, J. Christopher; Wiglesworth, Kristin E.; Girard, Kevin P.; Makowski, Teresa M.; Sach, Neal W.; Mustakis, Jason G.; Mehta, Ruchi; Trujillo, John I.; Chen, Xiaofeng; Li, Tangqing; Shi, Feng; Xie, Chengfu; Zhang, Qing. And the article was published in Organic Process Research & Development in 2019. Safety of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine The author mentioned the following in the article:

A scalable process for PF-06651600 was developed through successful enabling of the first generation synthesis. The synthesis highlights include the following: (1) replacement of costly PtO2 with a less expensive 5% Rh/C catalyst for a pyridine hydrogenation, (2) identification of a diasteromeric salt crystallization to isolate the enantiomerically pure cis-isomer directly from a racemic mixture of cis/trans isomers, (3) a high yielding amidation via Schotten-Baumann conditions, and (4) critical development of a reproducible crystallization procedure for a stable crystalline salt 1-((2S,5R)-5-((7H-Pyrrolo[2,3-d]pyrimidin-4-yl)amino)-2-methylpiperidin-1-yl)prop-2-en-1-one p-Toluenesulfonate, which is suitable for long-term storage and tablet formulation. All chromatog. purifications, including two chiral SFC chromatog. separations, were eliminated. Combined with other improvements in each step of the synthesis, the overall yield was increased from 5% to 14%. Several multikilogram batches of the API were delivered to support clin. studies. In the experiment, the researchers used 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Safety of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine)

2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4) belongs to pyrimidine. The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives, including the nucleotides cytosine, thymine and uracil, thiamine (vitamin B1) and alloxan. Safety of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

The author of 《Early Process Development of an Irreversible Epidermal Growth Factor Receptor (EGFR) T790 M Inhibitor》 were Tao, Yong; Keene, Nandell F.; Wiglesworth, Kristin E.; Sitter, Barbara; McWilliams, J. Christopher. And the article was published in Organic Process Research & Development in 2019. Electric Literature of C6H3Cl2N3 The author mentioned the following in the article:

The original synthesis of the irreversible epidermal growth factor receptor (EGFR) T790 M inhibitor 1 (I) was enabled by successful application of ammonium hydroxide to cleanly cleave the N-hydroxymethyl group and by development of high yielding conditions for the subsequent amidation reaction. Furthermore, a protection-free and regioselective new synthetic route was developed that shortened the synthesis from the original 8 steps to 6 steps and improved the overall yield from 5% to 34% on scale. Crystallizations of 1 and intermediates were correspondingly developed to control the quality en route. After reading the article, we found that the author used 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Electric Literature of C6H3Cl2N3)

2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4) belongs to pyrimidine. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own. Electric Literature of C6H3Cl2N3They have been used in a wide variety of pharmaceuticals including general anesthetics, anti-epilepsy medication, anti-malaria medication, drugs for treating high blood pressure, and HIV medication.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2017,Thorarensen, Atli; Dowty, Martin E.; Banker, Mary Ellen; Juba, Brian; Jussif, Jason; Lin, Tsung; Vincent, Fabien; Czerwinski, Robert M.; Casimiro-Garcia, Agustin; Unwalla, Ray; Trujillo, John I.; Liang, Sidney; Balbo, Paul; Che, Ye; Gilbert, Adam M.; Brown, Matthew F.; Hayward, Matthew; Montgomery, Justin; Leung, Louis; Yang, Xin; Soucy, Sarah; Hegen, Martin; Coe, Jotham; Langille, Jonathan; Vajdos, Felix; Chrencik, Jill; Telliez, Jean-Baptiste published 《Design of a Janus Kinase 3 (JAK3) Specific Inhibitor 1-((2S,5R)-5-((7H-Pyrrolo[2,3-d]pyrimidin-4-yl)amino)-2-methylpiperidin-1-yl)prop-2-en-1-one (PF-06651600) Allowing for the Interrogation of JAK3 Signaling in Humans》.Journal of Medicinal Chemistry published the findings.Synthetic Route of C6H3Cl2N3 The information in the text is summarized as follows:

Significant work has been dedicated to the discovery of JAK kinase inhibitors resulting in several compounds entering clin. development and two FDA approved NMEs. However, despite significant effort during the past two decades, identification of highly selective JAK3 inhibitors has eluded the scientific community. A significant effort within the research organization has resulted in the identification of the first orally active JAK3 specific inhibitor, which achieves JAK isoform specificity through covalent interaction with a unique JAK3 residue Cys-909. The relatively rapid resynthesis rate of the JAK3 enzyme presented a unique challenge in the design of covalent inhibitors with appropriate pharmacodynamics properties coupled with limited unwanted off-target reactivity. This effort resulted in the identification of PF-06651600 I, a potent and low clearance compound with demonstrated in vivo efficacy. The favorable efficacy and safety profile of this specific JAK3 inhibitor I led to its evaluation in several human clin. studies. In the experiment, the researchers used 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Synthetic Route of C6H3Cl2N3)

2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4) belongs to pyrimidine. Pyrimidine nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics. Synthetic Route of C6H3Cl2N3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2017,Xie, Hui; Zeng, Shaogao; He, Yuwen; Zhang, Guicheng; Yu, Pengjiu; Zhong, Guifa; Xu, Hongjiang; Yang, Ling; Wang, Shanchun; Zhao, Xin; Hu, Wenhui published 《Rapid generation of a novel DPP-4 inhibitor with long-acting properties: SAR study and PK/PD evaluation》.European Journal of Medicinal Chemistry published the findings.Related Products of 90213-66-4 The information in the text is summarized as follows:

Drug compliance is critical for patients with chronic diseases such as diabetes. In our continuous effort to find better glucose-lowering agents, an exploration for long-acting DPP-4 inhibitors had been launched. Based on our previously reported compounds bearing a pyrrolopyrimidine scaffold, the lead compound 4a (IC50 = 2.3 nM, t1/2(rat) = 5.46 h) with pharmacokinetic superiority was rapidly determined Further SAR study indicated that the pyrrole ring was generally tolerable for variation, in which a β-substitution gave a better DPP-4 affinity. In depth evaluation of the pyrrole ring β position identified a highly potent compound 12a (IC50 = 0.76 nM, t1/2(rat) = 7.89 h). In vivo pharmacodynamics tests demonstrated similar or even slightly better sustained DPP-4 inhibition for compounds 4a and 12a compared with the first marketed once-weekly drug trelagliptin in this category, indicating that improvements to DPP-4 inhibitory activity or pharmacokinetic profile might be feasible ways to rapidly generate long-acting DPP-4 inhibitors. The experimental process involved the reaction of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Related Products of 90213-66-4)

2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4) belongs to pyrimidine. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own. Related Products of 90213-66-4They have been used in a wide variety of pharmaceuticals including general anesthetics, anti-epilepsy medication, anti-malaria medication, drugs for treating high blood pressure, and HIV medication.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2017,Li, Wenlu; Sun, Qinsheng; Song, Lu; Gao, Chunmei; Liu, Feng; Chen, Yuzong; Jiang, Yuyang published 《Discovery of 1-(3-aryl-4-chlorophenyl)-3-(p-aryl)urea derivatives against breast cancer by inhibiting PI3K/Akt/mTOR and Hedgehog signalings》.European Journal of Medicinal Chemistry published the findings.Name: 2,4,6-Trichloropyrimidine The information in the text is summarized as follows:

PI3K/Akt/mTOR and hedgehog (Hh) signalings are two important pathways in breast cancer, which are usually connected with the drug resistance and cancer migration. Many studies indicated that PI3K/Akt/mTOR inhibitors and Hh inhibitors displayed synergistic effects, and the combination of the two signaling drugs could delay drug resistance and inhibit cancer migration in breast cancer. Therefore, the development of mols. simultaneously inhibiting these two pathways is urgent needed. Based on the structures of PI3K inhibitor buparlisib and Hh inhibitor vismodegib, a series of hybrid structures were designed and synthesized utilizing rational drug design and computer-based drug design. Several compounds displayed excellent antiproliferative activities against several breast cancer cell lines, including triple-neg. breast cancer (TNBC) MDA-MB-231 cell. Further mechanistic studies demonstrated that the representative compound 9i could inhibit both PI3K/Akt/mTOR and hedgehog (Hh) signalings by inhibiting the phosphorylation of S6K and Akt as well as decreasing the SAG elevated expression of Gli1. Compound 9i could also induce apoptosis remarkably in T47D and MDA-MB-231 cells. In the transwell assay, 9i showed significant inhibition on the migration of MDA-MB-231. After reading the article, we found that the author used 2,4,6-Trichloropyrimidine(cas: 3764-01-0Name: 2,4,6-Trichloropyrimidine)

2,4,6-Trichloropyrimidine(cas: 3764-01-0) is a member of organic chlorides. Almost all organochlorine compounds are synthesized. It is widely used as intermediates, solvents and pesticides of chemical synthetic products.Name: 2,4,6-Trichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 1988,Saxena, Naveen K.; Hagenow, Brenda M.; Genzlinger, Gail; Turk, Steven R.; Drach, John C.; Townsend, Leroy B. published 《Synthesis and antiviral activity of certain 4-substituted and 2,4-disubstituted 7-[(2-hydroxyethoxy)methyl]pyrrolo[2,3-d]pyrimidines》.Journal of Medicinal Chemistry published the findings.Product Details of 90213-66-4 The information in the text is summarized as follows:

Alkylation of the Na salt of pyrimidine I (R = MeS, R1 = H) with AcOCH2CH2OCH2Br gave I (R = MeS, R1 = AcOCH2CH2OCH2) which was converted into the title pyrimidines II (R = MeS, R2 = Cl, NH2; R = H, OH, MeSO2, MeO, R2 = NH2). Similarly, I (R = Cl, NHAc, R1 = H) were alkylated and further transformed into II (R = Cl, R2 = Cl, NH2; R = NHAc, R2 = Cl; R = R2 = NH2). In tests of II involving human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1), only slight activity and cytotoxicity were observed The most active compounds I(R = Cl, R1 = AcOCH2CH2OCH2) and II (R = R2 = Cl), were slightly more active against HCMV than acyclovir, but both compounds were inactive against HSV-1. The activity against HCMV, however, was not well separated from cytotoxicity leading to the conclusion that these compounds did not merit further study. In the experimental materials used by the author, we found 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Product Details of 90213-66-4)

2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4) belongs to pyrimidine. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own. Product Details of 90213-66-4They have been used in a wide variety of pharmaceuticals including general anesthetics, anti-epilepsy medication, anti-malaria medication, drugs for treating high blood pressure, and HIV medication.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Brakta, Mohamed; Daves, G. Doyle Jr. published their research in Journal of the Chemical Society on August 7 ,1992. The article was titled 《Efficient synthesis of 3H,5H-pyrrolo[3,2-d]pyrimidin-4-one》.Computed Properties of C5H4ClN3O3 The article contains the following contents:

Palladium-catalyzed cross-coupling of 4-iodo-6-methoxy-5-nitropyrmidine and trimethyl(tributylstannylethynyl)silane to form the corresponding 4-(trimethylsilylethynyl)pyrimidine I and subsequent construction of an annellated pyrrolo ring II provides an efficient route to the title pyrrolo[3,2-d]pyrimidine system III. In the experiment, the researchers used many compounds, for example, 4-Chloro-6-methoxy-5-nitropyrimidine(cas: 52854-14-5Computed Properties of C5H4ClN3O3)

4-Chloro-6-methoxy-5-nitropyrimidine(cas: 52854-14-5) is a member of organic chlorides. Organic chlorides are compounds containing a carbon-chlorine bond, which are widely used in the oil field as a wax dissolver. They are generally not present in crude oils and are typically the result of additives, cleaning solutions or chemicals used for oil recovery.Computed Properties of C5H4ClN3O3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Marcelis, A. T. M.; Van der Plas, H. C.; Harkema, S. published an article on January 25 ,1985. The article was titled 《Ring transformations of heterocycles with nucleophiles. 32. Cycloadditions of 5-nitropyrimidines with ynamines. Synthesis and crystal structure of a 2,2a-dihydroazeto[2,3-d]-3,5-diazocine, a novel heterocycle》, and you may find the article in Journal of Organic Chemistry.Synthetic Route of C5H5N3O3 The information in the text is summarized as follows:

5-Nitropyrimidine and its 2-Me, 2-Ph and 2-methoxy derivatives react with 1-(diethylamino)propyne to yield 2,2a-dihydroazeto[2,3-d]-3,5-diazocine 1-oxides I (R = H, Me, Ph, OMe). The crystal structure of N,N-diethyl-2,2a-dihydro-2,4,7-trimethyl-6-(diethylamino)azeto[2,3-d]-3,5-diazocine-2-carboxamide 1-oxide was determined The mechanism for the formation of this novel type of heterocycle is discussed. The experimental part of the paper was very detailed, including the reaction process of 2-Methoxy-5-nitropyrimidine(cas: 14001-69-5Synthetic Route of C5H5N3O3)

2-Methoxy-5-nitropyrimidine(cas: 14001-69-5) is a member of ether. Friedel Crafts reaction, for example, adds an alkyl or acyl group to aromatic ethers when they react with an alkyl or acyl halide in the presence of a Lewis acid as a catalyst.Synthetic Route of C5H5N3O3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Marcelis, A. T. M.; Van der Plas, H. C. published an article on January 10 ,1986. The article was titled 《Ring transformations of heterocycles with nucleophiles. 33. Cycloadditions of 5-nitropyrimidines with ynamines. Formation of 3-nitropyridines, N-5-pyrimidyl-α-carbamoylnitrones, and 2,2a-dihydroazeto[2,3-d]-3,5-diazocines》, and you may find the article in Journal of Organic Chemistry.Formula: C6H7N3O4 The information in the text is summarized as follows:

The reaction of pyrimidines containing an electron-withdrawing substituent at C-5 with ynamines RCCR1 (I; R,R1 = Me, Et2N; Ph, Me2N; Ph, pyrrolidino) was studied. 5-(Ethoxycarbonyl)- and 5-(methylsulfonyl)pyridine undergo [4 + 2] cycloaddition to yield the substituted pyridines II and III resp. 5-Nitropyrimidines containing 2- and/or 4(6)-alkoxy or Me groups give a variety of products upon reaction with I. 4,6-Dimethoxy-5-nitropyrimidine undergoes [4 + 2] cycloaddition to give pyridine derivative IV (R2 = MeO) upon reaction with I (R = Me, R1 = Et2N) (V). Nitrone VI (R2 = MeO) is formed as main product upon reaction of V with 2,4-dimethoxy-5-nitropyrimidine. 5-Nitropyrimidines unsubstituted at C-4 and C-6 give dihydroazeto[2,3-d]diazocines upon reaction with 2 equiv of V. 4-Methoxy-5-nitropyrimidine yields pyridine IV and nitrone VI (R3 = H, R4 = MeO) upon reaction with V, and from 4-methyl-5-nitropyriidine, the pyridines IV (R2 = H, Me) dihydroazetodiazocine VII, and a nitrone are formed. Ynamine I (R = Ph; R1 = Me2N) is less reactive than V and does not react to form dihydroazetodiazocines with the 5-nitropyrimidines. Instead, nitrone VIII (R5 = H) and pyridine IX are formed upon reaction of I (R = Ph, R1 = Me2N) with 5-nitropyrimidine, and nitrone VIII (R5 = Ph) is formed with 2-phenyl-5-nitropyrimidine. In the experiment, the researchers used 2,4-Dimethoxy-5-nitropyrimidine(cas: 30561-07-0Formula: C6H7N3O4)

2,4-Dimethoxy-5-nitropyrimidine(cas: 30561-07-0) is a member of ether. When aromatic ethers are exposed to halogen in the presence or absence of a catalyst, they undergo halogenation, such as bromination.Formula: C6H7N3O4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2022,Fairhurst, Robin A.; Furet, Pascal; Imbach-Weese, Patricia; Stauffer, Frederic; Rueeger, Heinrich; McCarthy, Clive; Ripoche, Sebastien; Oswald, Susanne; Arnaud, Bertrand; Jary, Aline; Maira, Michel; Schnell, Christian; Guthy, Daniel A.; Wartmann, Markus; Kiffe, Michael; Desrayaud, Sandrine; Blasco, Francesca; Widmer, Toni; Seiler, Frank; Gutmann, Sascha; Knapp, Mark; Caravatti, Giorgio published an article in Journal of Medicinal Chemistry. The title of the article was 《Identification of NVP-CLR457 as an Orally Bioavailable Non-CNS-Penetrant pan-Class IA Phosphoinositol-3-Kinase Inhibitor》.Quality Control of 2,4,6-Trichloropyrimidine The author mentioned the following in the article:

Balanced pan-class I phosphoinositide 3-kinase inhibition as an approach to cancer treatment offers the prospect of treating a broad range of tumor types and/or a way to achieve greater efficacy with a single inhibitor. Taking buparlisib as the starting point, the balanced pan-class I PI3K inhibitor 40 (NVP-CLR457) was identified with what was considered to be a best-in-class profile. Key to the optimization to achieve this profile was eliminating a microtubule stabilizing off-target activity, balancing the pan-class I PI3K inhibition profile, minimizing CNS penetration, and developing an amorphous solid dispersion formulation. A rationale for the poor tolerability profile of 40 in a clin. study is discussed. The experimental process involved the reaction of 2,4,6-Trichloropyrimidine(cas: 3764-01-0Quality Control of 2,4,6-Trichloropyrimidine)

2,4,6-Trichloropyrimidine(cas: 3764-01-0) is a member of organic chlorides. Organic chloride content in crude oil can be detected through specialized laboratory analysis. Care and attention are essential while sampling and testing.Quality Control of 2,4,6-Trichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia