{"id":5738,"date":"2021-08-06T03:22:28","date_gmt":"2021-08-05T19:22:28","guid":{"rendered":"https:\/\/www.pyrazoles-derivatives.com\/?p=5738"},"modified":"2021-08-06T03:22:28","modified_gmt":"2021-08-05T19:22:28","slug":"discovery-of-5334-39-4","status":"publish","type":"post","link":"https:\/\/www.pyrazoles-derivatives.com\/?p=5738","title":{"rendered":"Discovery of  5334-39-4"},"content":{"rendered":"<p><a href=\"https:\/\/www.ambeed.com\/products\/5334-39-4.html\">Related Products of 5334-39-4<\/a>, These common heterocyclic compound, 5334-39-4, name is 3-Methyl-4-nitro-1H-pyrazole, 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.<\/p>\n<p>To a solution of 5-hydroxy-l-methyl-piperidin-2-one (175 nig, 1.35 mniol) , 3 -methyl -4-nitro-lH-pyrazole (5) (205.9 rag, 1.62 mmol) and PPh3 (531.14 mg, 2.03 mmol) in THF (15 mL) was added DIAD (409.48 mg, 2.03 mmol) at 0 C. The mixture was stirred at 25 C for 12 h. The reaction mixture was concentrated under reduced pressure to get a residue, which was purified by prep-TLC (Si02, DCM: MeOH :=: 20: 1) to give a mixture of l-methyl-5-(5-methyl-4-nitro-lH- pyrazol-l-yl)piperidin-2-one and l-methyl-5-(3-methyl-4-iiitro-lH-pyrazol-l-yl)piperidin-2-one as yellow solid, LCMS: RT 0,577 min, m\/z = 239.1 [M+H . To a mixture of l-methyl-5-(5-methyl-4-nitro-lH-pyrazol- l-yl)piperidin-2-one and l-methyl-5-(3-methyl-4-nitro-lH-pyrazol-l-yl)piperidin-2-one (180 mg, 755.54 muetaiotaomicron) in MeOH (10 mL) was added Pd\/C (10%, 60 mg) under 2. The suspension was degassed and purged with H2 for 3 times. The mixture was stirred under H2 (15 Psi) at 25 C for 4 h. It was filtered over celite, the filter cake was washed wtih MeOH (20 mL chi 2), the filtrate was combined and concentrated under reduced pressure to give a mixture of 5-(4-amino-5-meth}7l-lH-pyrazol-l-yl)-l-methylpiperidin-2- one and 5-(4-amino-3-methyl-lH-pyrazol-l -yl)-l -methylpiperidin-2-one (as yellow oil. LCMS: RT 0.194 mm, m\/z = 209.1 [M+H]+. A mixture of 5-(4~amino-5~ methyl- lH-pyrazol-l-yl)-l-methylpiperidm-2-one and 5-(4-amino-3-methyl-lH-pyrazol-l-y])-l- methylpiperidin-2-one (107 mg, 513.78 mupiiotaomicron), 4-cyclopropyl-2-methylsulfonyl-5- (trifluoromethyl)pyrimidine (137 mg, 513.78 muetaiotaomicron) and TsQH.HjQ (49 mg, 256.89 mupiiotaomicron) in 1,4-dioxane (15 mL) was degassed and purged with N2 for 3 times, and then the m ixture was stirred at 100 C for 2 h under N2. It was poured into H20 (15 mL), adjusted to pH = 8 with aq, NaHC03, extracted wtih EtOAc (2 x 30 mL). The combined organic phase was dried over Na2S04, filtered and concentrated under reduced pressure to get a residue, which was purified by prep-HPLC (neutral) first and then it was re- purified by SFC to give 5-(4-((4-cyclopropyl-5-(trifluoromethyl)pyrimidin-2-yl)amino)-5-methyl-lH- pyrazol-1 -yl)-l -methylpiperidin-2-one (14 mg) and 5-(4-((4-cyc]opropyl-5-(tri\u00a3luoromethyl)pyrimidin-2- yl)amino)-3 -methyl- 1 H-pyrazol- 1 -yl)- 1 -methylpiperidin-2-one . 5-(4-((4-cyclopropyl-5-(trifluoromethyl)pyrimidin-2-yl)amino)-5-methyl-lH-pyrazol-l-yl)-l- methylpiperidin-2-one (A-26):  H MR (400 MHz, CDC13): 3 8.39 (s, IH), 7.67 (br, s . 1H), 6.51 (br. s, H), 4.42 &#8211; 4.60 (m, IH), 3.91 (dd, J = 1 1.69, 9,92 Hz, 1H), 3.46 (ddd, J = 12.13, 5 ,51 , 1 ,76 Hz, IH), 3.00 (s, 3H), 2.65 (d, J &#8212;&#8212;- 3.97 Hz, 1H), 2.42 &#8211; 2.59 (m, 11 1 ). 2.25 (s, 3H), 2.17 (d. .\/ 1.76 Hz, 2H), 1.22 (br. s.,2H), 1.09 (dd, J = 7.72, 3.31Hz, 2H). HPLC: Retention Time: 2.87 min. MS: (M+lT) m\/z. 395.2. 5-(4-((4-cyclopropyl-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-methyl-lH-pyrazol-l-yl)-l- methylpiperidin-2-one (A-27): MR (400 MHz, CDC13): delta 8.43 (s, IH), 7.86 (br, s,, IH), 6,49 &#8211; 6.87 (m, IH), 4.56 id. .\/ 6.62 Hz, IH), 3.71 (d, .\/ 7.06 Hz, 21 1 ). 3.00 (s, 3H), 2.48 &#8211; 2.64 (m, 2H), 2.34 &#8211; 2.45 (m, IH), 2.17 \u00b7\u00b7 2.34 (m, 4H), 1.22 &#8211; 1.30 (m, 21 1 ). 1.15 (br. s., 2H). HPLC: Retention Time: 2.86 m in. MS: ( M l ) m\/z: 395.2.<\/p>\n<p>Statistics shows that 3-Methyl-4-nitro-1H-pyrazole is playing an increasingly important role. we look forward to future research findings about 5334-39-4.<\/p>\n<p>Reference:<br \/><a href=\"http:\/\/v3.espacenet.com\/textdoc?DB=EPODOC&#038;IDX=WO2017087905&#038;F=0\">Patent; DENALI THERAPEUTICS INC.; ESTRADA, Anthony A.; FENG, Jianwen A.; LYSSIKATOS, Joseph P.; SWEENEY, Zachary K.; DE VICENTE FIDALGO, Javier; (271 pag.)WO2017\/87905; (2017); A1;<\/a>,<br \/><a href=\"https:\/\/en.wikipedia.org\/wiki\/Pyrazole\">Pyrazole &#8211; Wikipedia<\/a>,<br \/><a href=\"https:\/\/www.sciencedirect.com\/topics\/chemistry\/pyrazoles\">Pyrazoles &#8211; an overview | ScienceDirect Topics<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Statistics shows that 3-Methyl-4-nitro-1H-pyrazole is playing an increasingly important role. we look forward to future research findings about 5334-39-4.<\/p>\n","protected":false},"author":8,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[216,131],"tags":[126],"class_list":["post-5738","post","type-post","status-publish","format-standard","hentry","category-5334-39-4","category-pyrazoles-derivatives","tag-m-w100-200"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v24.9 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Discovery of<\/title>\n<meta name=\"description\" content=\"Related Products of 5334-39-4, These common heterocyclic compound, 5334-39-4, name is 3-Methyl-4-nitro-1H-pyrazole, 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.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"http:\/\/www.pyrazoles-derivatives.com\/?p=5738\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Discovery of\" \/>\n<meta property=\"og:description\" content=\"Related Products of 5334-39-4, These common heterocyclic compound, 5334-39-4, name is 3-Methyl-4-nitro-1H-pyrazole, 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.\" \/>\n<meta property=\"og:url\" content=\"http:\/\/www.pyrazoles-derivatives.com\/?p=5738\" \/>\n<meta property=\"og:site_name\" content=\"pyrazoles-derivatives\" \/>\n<meta property=\"article:published_time\" content=\"2021-08-05T19:22:28+00:00\" \/>\n<meta name=\"author\" content=\"Jessica.F\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Jessica.F\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"3 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"http:\/\/www.pyrazoles-derivatives.com\/?p=5738\",\"url\":\"http:\/\/www.pyrazoles-derivatives.com\/?p=5738\",\"name\":\"Discovery of\",\"isPartOf\":{\"@id\":\"https:\/\/www.pyrazoles-derivatives.com\/#website\"},\"datePublished\":\"2021-08-05T19:22:28+00:00\",\"author\":{\"@id\":\"https:\/\/www.pyrazoles-derivatives.com\/#\/schema\/person\/d9a9f27bed675392c6f363a01ffd49f1\"},\"description\":\"Related Products of 5334-39-4, These common heterocyclic compound, 5334-39-4, name is 3-Methyl-4-nitro-1H-pyrazole, 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.\",\"breadcrumb\":{\"@id\":\"http:\/\/www.pyrazoles-derivatives.com\/?p=5738#breadcrumb\"},\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"http:\/\/www.pyrazoles-derivatives.com\/?p=5738\"]}]},{\"@type\":\"BreadcrumbList\",\"@id\":\"http:\/\/www.pyrazoles-derivatives.com\/?p=5738#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"\u9996\u9875\",\"item\":\"https:\/\/www.pyrazoles-derivatives.com\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Discovery of 5334-39-4\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\/\/www.pyrazoles-derivatives.com\/#website\",\"url\":\"https:\/\/www.pyrazoles-derivatives.com\/\",\"name\":\"pyrazoles-derivatives\",\"description\":\"Several pyrazole derivatives possess important pharmacological activities and they have been proved useful materials in drug research. 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