Category: 945244-29-1

Henry, James R. et al. published their research in Journal of Medicinal Chemistry in 2015 | CAS: 945244-29-1

5-Bromo-2-fluoro-4-methylaniline (cas: 945244-29-1) belongs to organobromine compounds. Many of the organo bromine compounds are relatively nonpolar. Bromine is more electronegative than carbon (2.8 vs 2.5) and hence the carbon in a carbon鑱砨romine bond is electrophilic in nature. Many of the alkyl bromine derivatives are excellent alkylating agents since bromides are good leaving groups. Tribromides, like tetrabutylammonium tribromide, are used as a solid source of bromine. N-bromosuccimide (NBS) is used for the selective bromination of allylic bonds.Recommanded Product: 5-Bromo-2-fluoro-4-methylaniline

Discovery of 1-(3,3-Dimethylbutyl)-3-(2-fluoro-4-methyl-5-(7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl)phenyl)urea (LY3009120) as a Pan-RAF Inhibitor with Minimal Paradoxical Activation and Activity against BRAF or RAS Mutant Tumor Cells was written by Henry, James R.;Kaufman, Michael D.;Peng, Sheng-Bin;Ahn, Yu Mi;Caldwell, Timothy M.;Vogeti, Lakshminarayana;Telikepalli, Hanumaiah;Lu, Wei-Ping;Hood, Molly M.;Rutkoski, Thomas J.;Smith, Bryan D.;Vogeti, Subha;Miller, David;Wise, Scott C.;Chun, Lawrence;Zhang, Xiaoyi;Zhang, Youyan;Kays, Lisa;Hipskind, Philip A.;Wrobleski, Aaron D.;Lobb, Karen L.;Clay, Julia M.;Cohen, Jeffrey D.;Walgren, Jennie L.;McCann, Denis;Patel, Phenil;Clawson, David K.;Guo, Sherry;Manglicmot, Danalyn;Groshong, Chris;Logan, Cheyenne;Starling, James J.;Flynn, Daniel L.. And the article was included in Journal of Medicinal Chemistry in 2015.Recommanded Product: 5-Bromo-2-fluoro-4-methylaniline This article mentions the following:

The RAS-RAF-MEK-MAPK cascade is an essential signaling pathway, with activation typically mediated through cell surface receptors. The kinase inhibitors vemurafenib and dabrafenib, which target oncogenic BRAF V600E, have shown significant clin. efficacy in melanoma patients harboring this mutation. Because of paradoxical pathway activation, both agents were demonstrated to promote growth and metastasis of tumor cells with RAS mutations in preclin. models and are contraindicated for treatment of cancer patients with BRAF WT background, including patients with KRAS or NRAS mutations. To eliminate the issues associated with paradoxical MAPK pathway activation and to provide therapeutic benefit to patients with RAS mutant cancers, we sought to identify a compound not only active against BRAF V600E but also wild type BRAF and CRAF. On the basis of its superior in vitro and in vivo profile, compound 13 was selected for further development and is currently being evaluated in phase I clin. studies. In the experiment, the researchers used many compounds, for example, 5-Bromo-2-fluoro-4-methylaniline (cas: 945244-29-1Recommanded Product: 5-Bromo-2-fluoro-4-methylaniline).

5-Bromo-2-fluoro-4-methylaniline (cas: 945244-29-1) belongs to organobromine compounds. Many of the organo bromine compounds are relatively nonpolar. Bromine is more electronegative than carbon (2.8 vs 2.5) and hence the carbon in a carbon鑱砨romine bond is electrophilic in nature. Many of the alkyl bromine derivatives are excellent alkylating agents since bromides are good leaving groups. Tribromides, like tetrabutylammonium tribromide, are used as a solid source of bromine. N-bromosuccimide (NBS) is used for the selective bromination of allylic bonds.Recommanded Product: 5-Bromo-2-fluoro-4-methylaniline

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Zhao, Peng et al. published their research in European Journal of Medicinal Chemistry in 2022 | CAS: 945244-29-1

5-Bromo-2-fluoro-4-methylaniline (cas: 945244-29-1) belongs to organobromine compounds. Most organobromine compounds, like most organohalide compounds, are relatively nonpolar. One prominent application of synthetic organobromine compounds is the use of polybrominated diphenyl ethers as fire-retardants, and in fact fire-retardant manufacture is currently the major industrial use of the element bromine.Formula: C7H7BrFN

Discovery of spiro amide SHR902275: A potent, selective, and efficacious RAF inhibitor targeting RAS mutant cancers was written by Zhao, Peng;Zhuang, Linghang;Wang, Xiangzhu;Huang, Song;Wu, Heping;Zhou, Yu;Yan, Yuna;Zhang, Fan;Shen, Ru;Li, Jing;Liu, Suxing;Zhang, Rumin;Dong, Ping;Mao, Yuchang;Fan, Yuanmin;He, Chunyong;Sun, Jiakang;Zhang, Lei;Hu, Qiyue;Wan, Hong;Feng, Jun;Bai, Chang;He, Feng;Tao, Weikang. And the article was included in European Journal of Medicinal Chemistry in 2022.Formula: C7H7BrFN This article mentions the following:

The RAS-RAF-MEK-ERK signaling pathway plays a key role to regulate multiple cellular functions. Acquired resistance to the first-generation RAF inhibitors that only targeted the bRAFV600E mutation prompted the need for a new generation of RAF inhibitors to target cancers bearing mutant RAS and wild type RAF activity by inhibition of paradoxical activation. Starting from the company’s previously reported RAF inhibitor 1 (I), extensive drug potency and drug-like properties optimizations led to the discovery of mol. 33 (SHR902275, II) with greatly improved in vitro potency and solubility Mol. 33 exhibited good DMPK (Drug Metabolism and Pharmacokinetics) properties, excellent permeability, and outstanding mouse/rat oral PK. It was further evaluated in an in vivo RAS mutant Calu6 xenograft mouse model and demonstrated dose dependent efficacy. To achieve high exposure in a toxicity study, pro-drug 48 (III) was also explored. In the experiment, the researchers used many compounds, for example, 5-Bromo-2-fluoro-4-methylaniline (cas: 945244-29-1Formula: C7H7BrFN).

5-Bromo-2-fluoro-4-methylaniline (cas: 945244-29-1) belongs to organobromine compounds. Most organobromine compounds, like most organohalide compounds, are relatively nonpolar. One prominent application of synthetic organobromine compounds is the use of polybrominated diphenyl ethers as fire-retardants, and in fact fire-retardant manufacture is currently the major industrial use of the element bromine.Formula: C7H7BrFN

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Henry, James R. et al. published their research in Journal of Medicinal Chemistry in 2015 | CAS: 945244-29-1

5-Bromo-2-fluoro-4-methylaniline (cas: 945244-29-1) belongs to organobromine compounds. Many of the organo bromine compounds are relatively nonpolar. Bromine is more electronegative than carbon (2.8 vs 2.5) and hence the carbon in a carbon–bromine bond is electrophilic in nature. Many of the alkyl bromine derivatives are excellent alkylating agents since bromides are good leaving groups. Tribromides, like tetrabutylammonium tribromide, are used as a solid source of bromine. N-bromosuccimide (NBS) is used for the selective bromination of allylic bonds.Recommanded Product: 5-Bromo-2-fluoro-4-methylaniline

Discovery of 1-(3,3-Dimethylbutyl)-3-(2-fluoro-4-methyl-5-(7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl)phenyl)urea (LY3009120) as a Pan-RAF Inhibitor with Minimal Paradoxical Activation and Activity against BRAF or RAS Mutant Tumor Cells was written by Henry, James R.;Kaufman, Michael D.;Peng, Sheng-Bin;Ahn, Yu Mi;Caldwell, Timothy M.;Vogeti, Lakshminarayana;Telikepalli, Hanumaiah;Lu, Wei-Ping;Hood, Molly M.;Rutkoski, Thomas J.;Smith, Bryan D.;Vogeti, Subha;Miller, David;Wise, Scott C.;Chun, Lawrence;Zhang, Xiaoyi;Zhang, Youyan;Kays, Lisa;Hipskind, Philip A.;Wrobleski, Aaron D.;Lobb, Karen L.;Clay, Julia M.;Cohen, Jeffrey D.;Walgren, Jennie L.;McCann, Denis;Patel, Phenil;Clawson, David K.;Guo, Sherry;Manglicmot, Danalyn;Groshong, Chris;Logan, Cheyenne;Starling, James J.;Flynn, Daniel L.. And the article was included in Journal of Medicinal Chemistry in 2015.Recommanded Product: 5-Bromo-2-fluoro-4-methylaniline This article mentions the following:

The RAS-RAF-MEK-MAPK cascade is an essential signaling pathway, with activation typically mediated through cell surface receptors. The kinase inhibitors vemurafenib and dabrafenib, which target oncogenic BRAF V600E, have shown significant clin. efficacy in melanoma patients harboring this mutation. Because of paradoxical pathway activation, both agents were demonstrated to promote growth and metastasis of tumor cells with RAS mutations in preclin. models and are contraindicated for treatment of cancer patients with BRAF WT background, including patients with KRAS or NRAS mutations. To eliminate the issues associated with paradoxical MAPK pathway activation and to provide therapeutic benefit to patients with RAS mutant cancers, we sought to identify a compound not only active against BRAF V600E but also wild type BRAF and CRAF. On the basis of its superior in vitro and in vivo profile, compound 13 was selected for further development and is currently being evaluated in phase I clin. studies. In the experiment, the researchers used many compounds, for example, 5-Bromo-2-fluoro-4-methylaniline (cas: 945244-29-1Recommanded Product: 5-Bromo-2-fluoro-4-methylaniline).

5-Bromo-2-fluoro-4-methylaniline (cas: 945244-29-1) belongs to organobromine compounds. Many of the organo bromine compounds are relatively nonpolar. Bromine is more electronegative than carbon (2.8 vs 2.5) and hence the carbon in a carbon–bromine bond is electrophilic in nature. Many of the alkyl bromine derivatives are excellent alkylating agents since bromides are good leaving groups. Tribromides, like tetrabutylammonium tribromide, are used as a solid source of bromine. N-bromosuccimide (NBS) is used for the selective bromination of allylic bonds.Recommanded Product: 5-Bromo-2-fluoro-4-methylaniline

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Zhao, Peng et al. published their research in European Journal of Medicinal Chemistry in 2022 | CAS: 945244-29-1

5-Bromo-2-fluoro-4-methylaniline (cas: 945244-29-1) belongs to organobromine compounds. Most organobromine compounds, like most organohalide compounds, are relatively nonpolar. One prominent application of synthetic organobromine compounds is the use of polybrominated diphenyl ethers as fire-retardants, and in fact fire-retardant manufacture is currently the major industrial use of the element bromine.Formula: C7H7BrFN

Discovery of spiro amide SHR902275: A potent, selective, and efficacious RAF inhibitor targeting RAS mutant cancers was written by Zhao, Peng;Zhuang, Linghang;Wang, Xiangzhu;Huang, Song;Wu, Heping;Zhou, Yu;Yan, Yuna;Zhang, Fan;Shen, Ru;Li, Jing;Liu, Suxing;Zhang, Rumin;Dong, Ping;Mao, Yuchang;Fan, Yuanmin;He, Chunyong;Sun, Jiakang;Zhang, Lei;Hu, Qiyue;Wan, Hong;Feng, Jun;Bai, Chang;He, Feng;Tao, Weikang. And the article was included in European Journal of Medicinal Chemistry in 2022.Formula: C7H7BrFN This article mentions the following:

The RAS-RAF-MEK-ERK signaling pathway plays a key role to regulate multiple cellular functions. Acquired resistance to the first-generation RAF inhibitors that only targeted the bRAFV600E mutation prompted the need for a new generation of RAF inhibitors to target cancers bearing mutant RAS and wild type RAF activity by inhibition of paradoxical activation. Starting from the company’s previously reported RAF inhibitor 1 (I), extensive drug potency and drug-like properties optimizations led to the discovery of mol. 33 (SHR902275, II) with greatly improved in vitro potency and solubility Mol. 33 exhibited good DMPK (Drug Metabolism and Pharmacokinetics) properties, excellent permeability, and outstanding mouse/rat oral PK. It was further evaluated in an in vivo RAS mutant Calu6 xenograft mouse model and demonstrated dose dependent efficacy. To achieve high exposure in a toxicity study, pro-drug 48 (III) was also explored. In the experiment, the researchers used many compounds, for example, 5-Bromo-2-fluoro-4-methylaniline (cas: 945244-29-1Formula: C7H7BrFN).

5-Bromo-2-fluoro-4-methylaniline (cas: 945244-29-1) belongs to organobromine compounds. Most organobromine compounds, like most organohalide compounds, are relatively nonpolar. One prominent application of synthetic organobromine compounds is the use of polybrominated diphenyl ethers as fire-retardants, and in fact fire-retardant manufacture is currently the major industrial use of the element bromine.Formula: C7H7BrFN

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Extended knowledge of 945244-29-1

The synthetic route of 945244-29-1 has been constantly updated, and we look forward to future research findings.

945244-29-1, name is 5-Bromo-2-fluoro-4-methylaniline, belongs to bromides-buliding-blocks compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. SDS of cas: 945244-29-1

Method B: To 4 necked round bottom flask, equipped with mechanical agitation, thermometer, and N2 inlet is added 5-bromo-2-fiuoro-4-methylaniline (200g, 0.98 mol), CH3COOK (192g, 1.95 mol, 2.0eq), bis(pinacolato)diboron (248g, 0.98 mol,1.0eq) and IPAC (3L). After degassing with N2 for 30 min, the mixture is warmed to 50C and Pd(dppf)Cl2 (8g, 4wt%) is added. The reaction mixture is heated under reflux for at least lOh until the content of starting material <2% (GC). The mixture is cooled to 20~30C, filtered through a pad of Celite and rinsed with IPAC (1L). The filtrate is concentrated to 400~500ml remaining. The residue is mixed with n-Heptane (700ml), filtered through a Si02 pad and eluted with IPAC/n-Heptane(l/5 first, ~2L, and then 2/5, ~3L ). The filtrate is concentrated to 350~400ml. n-Heptane (300ml) is added and the mixture is again concentrated to 350~400ml. The residue (suspension) is cooled to -10- -20C and filtered after stirring for 2- 5 h. The crude product is dissolved in MeOH (200 ml) at 30-40 C, then slowly add H20 (600 ml) dropwise in 0.5~lh. The suspension is cooled to 20-30 C and filtered after stirring for 1-2 h .The solid is dried under high vacuum to afford the title compound as off- white solid (183g, 74% yield and 99% purity detected by UV absorption at 210 nm; 1H NMR (400 MHz, CDC13): delta 7.42 (d, J = 10.2 Hz, 1H), 7.01 (d, J = 12.4 Hz, 1H), 3.76 (s, 2H), 2.64 (s, 3H), 1.55 (s, 12H); 13C NMR(500MHz,CDC13): delta 20.66, 20.67, 24.40, 82.93, 116.20, 124.37, 130.64, 135.02, (151.93, 153.37);19F NMR (400 MHz,CDC13): delta 145.72 The synthetic route of 945244-29-1 has been constantly updated, and we look forward to future research findings. Reference:
Patent; ELI LILLY AND COMPANY; DECIPHERA PHARMACEUTICALS, LLC; ALLGEIER, Matthew Carl; FLYNN, Daniel L.; KAUFMAN, Michael D.; PATEL, Phenil J.; WOLFANGEL, Craig D.; WO2013/134243; (2013); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Simple exploration of 5-Bromo-2-fluoro-4-methylaniline

The synthetic route of 945244-29-1 has been constantly updated, and we look forward to future research findings.

Synthetic Route of 945244-29-1, A common heterocyclic compound, 945244-29-1, name is 5-Bromo-2-fluoro-4-methylaniline, molecular formula is C7H7BrFN, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

Combine 5-bromo-2-fluoro-4-methylaniline (3.1 g, 15.2 mmol), bis(pinacolato)diboron (4.24 g, 16.7 mmol), and potassium acetate (4.47 g, 45.6 mmol) in dioxane (40 mL) and sparge with argon. Add [l,l’-bis(diphenylphosphino)ferrocene]- dichloropalladium(II)-dichloromethane complex (0.620 g, 0.760 mmol), sparge again with argon and heat at 100C overnight. Filter the reaction mixture and concentrate in vacuo. Purify by silica gel chromatography (EtOAc/hexanes) to give the title compound (3.24 g, 85%). MS (m/z): 252.1 (M+ H+).

The synthetic route of 945244-29-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; DECIPHERA PHARMACEUTICALS, LLC; ELI LILLY AND COMPANY; FLYNN, Daniel L.; KAUFMAN, Michael D.; VOGETI, Lakshminarayana; WISE, Scott C.; LU, Wei-Ping; SMITH, Bryan D.; CALDWELL, Timothy M.; PATT, William C.; HENRY, James Robert; HIPSKIND, Philip Arthur; PENG, Sheng-Bin; WO2013/134298; (2013); A1;,
Bromide – Wikipedia,
bromide – Wiktionary