Day: August 13, 2021

Reference of 31728-75-3, A common heterocyclic compound, 31728-75-3, name is 1,5-Dimethyl-1H-pyrazole-4-carboxylic acid, molecular formula is C6H8N2O2, 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.

The 1.60g of 1,5-dimethyl -1H- pyrazole-4-carboxylic acid, 1.23 g of oxalyl chloride, approximately 15mg of N, N- dimethylformamide and 50mL of tetrahydrofuran was stirred at 25 1 hour. The reaction mixture was concentrated under reduced pressure to give 1,5-dimethyl -1H- pyrazole-4-carbonyl chloride.The 2.34 g of aluminum chloride in a mixture of 3.42g of sodium azide, and 50mL of tetrahydrofuran was stirred with heating under reflux for 2 hours. After ice-cooling the reaction mixture, the 1,5-dimethyl -1H- pyrazole-4-carboxamido mixture was added to the reaction mixture, followed by heating and stirring at reflux for 3 days. After cooling, the reaction mixture was added to 5.27g of sodium nitrite and a mixture of 100mL of water while stirring. The mixture was acidified with concentrated hydrochloric acid and then extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and then concentrated under reduced pressure to give 1.6g of 1- (1,5-dimethyl -1H- pyrazol-4-yl) -1,4-dihydro-tetrazole – 5-one.

The synthetic route of 31728-75-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Sumitomo Chemical Co., Ltd.; Dong, Xiuping; Gao, Qiaohuangshu; (181 pag.)CN105636955; (2016); A;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 1260243-04-6,Some common heterocyclic compound, 1260243-04-6, name is Ethyl 5-amino-1H-pyrazole-4-carboxylate, molecular formula is C6H9N3O2, 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.

General procedure: To a solution of the enamine compounds (2 a-c) (18.3mmol) in acetic acid (6 vol), ethyl 5-amino-1H-pyrazole-4-carboxylate (4) (18.3 mmol) was added lot wiseover a period of 15 min under nitrogen atmosphere. Thereaction mixture was allowed to heat to 110 °C for 6?8 h.Completion of the reactions was monitored by TLC. Aftercompletion of the reaction, excess amount of acetic acidwas removed under reduced pressure and the residueobtained was stirred with ice cold water for 30 min.The precipitated solid was filtered, washed with water anddried under vacuum. This crude product was further purifiedby column chromatography over silica gel (230?400 meshsize) eluted with 2?5percent of methanol in chloroform. Further,these compounds were crystallized from appropriatesolvents. 7-(2-Bromo-5-fluoro-phenyl)-pyrazolo [1, 5-a] pyrimidine-3-carboxylic acid ethyl ester (5a) This compound was obtained by condensation with ethyl 5-amino-1H-pyrazole-4-carboxylate and (2E)-1-(2-bromo-5-fluorophenyl)-3-(dimethylamino) prop-2-en-1-one (2a)under acetic acid heating. It was obtained as pale yellowsolid (5.7 g, 85percent). MP: 196.1?197.4 °C. IR (ATR, cm?1) upsilon:582.25 (C?Br), 1023.58 (C?F), 1063.45 (C?O), 1168.98(C?O), 1274.44 (C?N), 1460.15 (C?C), 1546.22 (C?C),1577.30 (C?C), 1700.63 (C=O), 3055.21 (C?H). 1H NMR(DMSO-d6 , 400 MHz) delta (ppm): 1.33 (3H, t, J = 7.2 Hz,ester?CH3), 4.44 (2H, q, J = 7.2 Hz, ester?CH2), 7.44 (1H,d, J = 4.4 Hz, pyrimidine-H), 7.48 (1H, t, J = 8.0 Hz,Ar?H), 7.68 (1H, dd, J1 = 3.4 Hz, J2 = 9.0 Hz, Ar?H), 7.9(1H, dd, J1 = 5.2 Hz, J2 = 9.0 Hz, Ar?H), 8.62 (1H, s,pyrazole?H), 8.97 (1H, d, J = 4.4 Hz, pyrimidine?H). 13CNMR (DMSO-d6, 100 MHz) delta (ppm): 14.99 (ester?CH3),60.02 (ester?CH2), 102.59 (pyrazole carbon), 111.89 (pyrimidinecarbon), 117.66 & 117.69 (d, 4J C-F = 3 Hz, ArCBr),119.35 & 119.60 (d, 2J C-F = 25 Hz, ArC), 119.85 &120.08 (d, 2J C-F = 23 Hz, ArC), 134.00 & 134.09 (d, 3J C-F= 9 Hz, ArC), 135.08 & 135.16 (d, 3J C-F = 8 Hz, ArC),145.63 (pyrazole carbon), 147.59 (pyrimidine carbon),147.84 (pyrimidine C-Ar), 153.62 (pyrazolo pyrimidinejunction carbon), 160.34 & 162.79 (d, 1J C-F = 245 Hz,ArC?F), 162.57 (?C = O). LC?MS (ESI, m/z): 367.2[M+2 H].

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Ethyl 5-amino-1H-pyrazole-4-carboxylate, its application will become more common.

Reference:
Article; Ajeesh Kumar; Bodke, Yadav D.; Lakra, Peter Serjious; Sambasivam, Ganesh; Bhat, Kishore G.; Medicinal Chemistry Research; vol. 26; 4; (2017); p. 714 – 744;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Related Products of 1150271-23-0, These common heterocyclic compound, 1150271-23-0, name is tert-Butyl 4-bromo-1H-pyrazole-1-carboxylate, 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.

In the reaction kettle, adding tetrahydrofuran 4.5 kg and 1 – BOC – 4 – brompyrazole (2.01 kg, 9.2 muM), stirring 0.5 hours, cooling to -20 C, maintain -10 C -0 C dropwise 3.2molBu3MgLi [preparation method: 1.0eq butyl magnesium chloride in -10 C -0 C lower drop by adding 2.0 equivalent butyl lithium in], TLC detection reaction, maintain the exchange completion -10 C -0 C dropwise dimethylamine fundamental frequency that mellow boron ester (1.61 kg, 9.4 muM) dissolved in 1 kg of the mixed solution in tetrahydrofuran, the completion of the dropping, thermal insulation 2 hours, natural heating stirring overnight. The control temperature of not more than 30 C after adding glacial acetic acid, after detecting the protecting group removal, stop stirring filtration, the mother liquor recovered, solid add triethylamine (1.01 kg, 10 muM) and ethyl acetate 8 kg after, heating to reflux reaction, the proportion of internal standard detecting product is not increased when, after lowering the filtering, the filtrate obtained after the distillation is a kind of white solid, by adding heptane cooling to 0 C beating, filtering, 50 – 60 C vacuum drying to obtain white solid pyrazole -4 – boric acid frequency that alcohol ester 1.36 kg, GC: 99.1%, HNMR consistent with the literature value, yield 76%.

The synthetic route of 1150271-23-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Cangzhou Puri Oriental Technology Co., Ltd; Leng, Yanguo; Gui, Qian; Shen, Haibing; (5 pag.)CN106188116; (2016); A;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 1260243-04-6, name is Ethyl 5-amino-1H-pyrazole-4-carboxylate, This compound has unique chemical properties. The synthetic route is as follows., SDS of cas: 1260243-04-6

To a solution of sodium ethoxide (520 mg, 7.6 mmol)In EtOH (20 mL)A solution of ethyl 3-amino-1H-pyrazole-4-carboxylate (1 g, 6.45 mmol) and 1,3-dimethyluracil (1.35 g, 9.68 mmol) were added sequentially.After the reaction system was stirred at 90 C for 3 hours,Move to an ice-water bath to cool and precipitate with amber. The filter cake was collected by filtration and washed with water (25 mL). The resulting solution was adjusted to pH = 7 with acetic acid and precipitated as a white solid which was filtered. Toluene (100 mL) was added to the resulting solid and dried in an ether to give the title compound as an off-white solid (900 mg, 67%).

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 1260243-04-6.

Reference:
Patent; Guangdong Dongyangguang Pharmaceutical Co., Ltd.; Jiatuo Sciences Corporation; Xi Ning; (88 pag.)CN104650092; (2017); B;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 330792-70-6, name is 3-Amino-5-(4-phenoxyphenyl)pyrazole-4-carbonitrile, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 330792-70-6

Step 5. Preparation of tert-butyl 3-(5-amino-4-cyano-3-(4-phenoxyphenyl)-1H-pyrazol-1-yl)piperidine-1-carboxylate To a solution of tert-butyl 3-(tosyloxy)piperidine-1-carboxylate (355 mg, 1.0 mmol) and 5-amino-3-(4-phenoxyphenyl)-1H-pyrazole-4-carbonitrile (276 mg, 1.0 mmol) in 5 mL of DMF is added Cs2CO3 (650 mg, 2.0 mmol). A tosyloxy leaving group is employed in this reaction. The mixture is stirred at RT for 16 hours, 75 C. for 3 hours and 60 C. for 16 hours. The mixture is concentrated washed with brine (100 mL*3) and dried over Na2SO4. The material is concentrated and purified by chromatography column on silica gel (eluted with petroleum ether/ethyl actate=3/1) to afford 60 mg (13%) of tert-butyl 3-(5-amino-4-cyano-3-(4-phenoxyphenyl)-1H-pyrazol-1-yl)piperidine-1-carboxylate as a yellow oil.

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 330792-70-6.

Reference:
Patent; Acerta Pharma B.V.; Lannutti, Brian; Rothbaum, Wayne; Barf, Tjeerd; Kaptein, Allard; (231 pag.)US2017/35881; (2017); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

288-13-1, name is 1H-Pyrazole, belongs to pyrazoles-derivatives compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. Application In Synthesis of 1H-Pyrazole

To a solution of Compound 1 (10 g, 72.5 mmol) in dry DMF (100 mL) were added pyrazole (10 g, 145 mmol), K2C03 (20 g, 145 mmol) and 18-crown-6 (2 g). The resulting solution was stirred at 130 C for 4 hours. After cooling to RT, the residue was treated with water and extracted with EA. The organic extracts were washed with water, brine, dried over anhydrous Na2SO4, filtered and concentrated to give a crude oil. The crude product was purified by recrystallization to afford Compound 2 (3.5 g, 26 %). 1HNMR (CDC13, 300 MHz) oe: 2.6-2.7 (s, 3 H), 6.4-6.5 (s, 1 H), 7.7-7.9 (m, 3 H), 8.0-8.2 (m, 3 H).

The synthetic route of 288-13-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; FORGE LIFE SCIENCE, LLC; REMISZEWSKI, Stacy; KOYUNCU, Emre; SUN, Qun; CHIANG, Lillian; (98 pag.)WO2016/77232; (2016); A2;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Some common heterocyclic compound, 3994-50-1, name is 1-Methyl-4-nitro-1H-pyrazole, molecular formula is C4H5N3O2, 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. Formula: C4H5N3O2

Example 25Synthesis of 4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-N-(1-methyl-1H-pyrazol-4-yl)-6-(4-morpholinyl)-1,3,5-triazin-2-amineThe compound was synthesized according to Method A.A mixture of 0.996 g (8.82 mmol) of 4-nitropyrazole (J. Med. Chem. 2005, 48, 5780-5793) and 1.33 g (10.6 mmol) of dimethyl sulphate in 10 mL of 1 M NaOH was heated at 35 C. for 48 hrs. The reaction mixture was cooled to RT and the precipitate was filtered, washed with water, and dried to give 0.561 g (50% yield) of 1-methyl-4-nitro-1H-pyrazole: 1H NMR (DMSO-d6) delta8.83 (s, 1H), 8.22 (s, 1H), 3.91 (s, 3H).A mixture of 0.144 g (1.14 mmol) 1-methyl-4-nitro-1H-pyrazole, 0.017 g (0.07 mmol) platinum oxide, and ethyl acetate (5 mL) in ethanol (15 mL) was stirred under 2 atmospheres of hydrogen for 14 hrs. The catalyst was removed by filtration through a pad of celite and the solvent was removed to give 0.080 mg (73% yield) of 4-amino-1-methyl-1H-pyrazole as a purple residue, which was used in the next step without further purification: 1H NMR (DMSO-d6) delta6.98 (s, 1H), 6.88 (s, 1H), 3.76 (br s, 2H), 3.65 (s, 3H).A mixture of 0.405 g (4.27 mmol) of 4-amino-1-methylpyrazole and 0.695 g (1.90 mmol) of 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-1H-benzimidazole in DMSO (5 mL) was heated at 125 C. for 15 min. The reaction mixture was cooled to room temperature and water was added. The solid was collected by filtration, washed with water, and dried. Chromatography on alumina, eluting with hexanes/EtOAc (1:1) gave a brown powder. Recrystallization from ethanol/CH2Cl2 gave 0.145 g (18% yield) of 4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-N-(1-methyl-1H-pyrazol-4-yl)-6-(4-morpholinyl)-1,3,5-triazin-2-amine: mp 225-226 C.; 1H NMR (DMSO-d6) (rotamers) delta10.00 (s, 1H), 9.73 (s, 0.2H), 8.60 (d, J=8.0 Hz, 1H), 8.29 (d, J=7.6 Hz, 0.2H), 7.92 (t, JHF=52.8 Hz, 1H), 7.86-7.80 (m, 2.6H), 7.68 (t, JHF=52.6 Hz, 0.2H), 7.59 (s, 1H), 7.52-7.42 (m, 2.9H), 3.85-3.82 (m, 8.4H), 3.75-3.73 (m, 4.8H); Anal. Calcd. for C19H19F2N9O 0.06EtOAc 0.24H2O: C, 52.9; H, 4.6; N, 28.8. Found: C, 52.9; H, 4.5; N, 28.6%.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3994-50-1, its application will become more common.

Reference:
Patent; Pathway Therapeutics Limited; US2011/9405; (2011); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 1239363-40-6,Some common heterocyclic compound, 1239363-40-6, name is 1-Cyclopropyl-4-iodo-1H-pyrazole, molecular formula is C6H7IN2, 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.

To a solution of 1-cyclopropyl-4-iodo-1H-pyrazole Intermediate 4a (500 mg, 2.13 mmol) in 1,4-dioxane (10 mL) was added benzyl mercaptan (527 mg, 4.30 mmol), NNdiisopropylethylamine (554 g, 4.30 mmol), tris(dibenzylideneacetone)dipalladium (20mg, 0.020 mmol) and 9,9-dimethyl-4, 5-bis(diphenylphosphino)xanthene (23 mg, 0.040 mmol) under nitrogen atmosphere. After stirred at 110 C overnight, the reaction mixture was cooled down to room temperature and diluted with water (20 mL), extracted with ethyl acetate (20 mL) for three times. The combined organic layers were washed with brine (20 mL), dried over Na2SO4() and filtered. The filtrate wasconcentrated under reduced pressure to give a crude product, which was purified by silica gel column chromatography (petroleum ether : ethyl acetate = 10 : 1) to to afford the title compound (330 mg, 67 % yield) as colorless oil. LC-MS (ESI): RT = 2.358 mm, mass calcd. for C13H14N2S 230.1, mlz found 230.9 [M+H]. ?HNIVII{ (300 1VIHz, CDC13)7.32-7.17 (m, 4H), 7.13 -7.07 (m, 3H), 3.78 (s, 2H), 3.57-3.46 (m, 1H), 1.07-0.92 (m, 4H).

The synthetic route of 1239363-40-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; JANSSEN PHARMACEUTICA NV; JOHNSON & JOHNSON (CHINA) INVESTMENT LTD.; WAN, Zhao-Kui; JIANG, Yimin; DAI, Xuedong; LIU, Qian; CHEUNG, Wing Shun; DENG, Gang; FU, Liqiang; (547 pag.)WO2019/1420; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 155600-99-0, name is 3,5-Dibromo-1-methyl-4-nitro-1H-pyrazole belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below. Safety of 3,5-Dibromo-1-methyl-4-nitro-1H-pyrazole

Nucleophilic aromatic substitution of the compound 2 with benzylamine in DMSO produces benzyl-(5-bromo-2-propyl-4-nitro-2H-pyrazol-3-yl)-amine 3.

The synthetic route of 155600-99-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Dahlgren, Richard Marc; Laidig, William David; Lim, Mu-ill; Murphy, Bryan Patrick; Zhang, Guiru; US2009/282622; (2009); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 82560-12-1,Some common heterocyclic compound, 82560-12-1, name is 3-Amino-5-tert-butylpyrazole, molecular formula is C7H13N3, 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.

A5. General Method for the Synthesis of BOC-Protected Pyrazoles 5-Amino-3-tert-butyl-N1-(tert-butoxycarbonyl)pyrazole: To a solution of 5-amino-3-tert-butylpyrazole (3.93 g, 28.2 mmol) in CH2Cl2 (140 mL) was added di-tert-butyl dicarbonate (6.22 g, 28.5 mmol) in one portion. The resulting solution was stirred at room temp. for 13 h, then diluted with EtOAc (500 mL). The organic layer was washed with water (2*300 mL), dried (MgSO4) and concentrated under reduced pressure. The solid residue was triturated (100 mL hexane) to give the desired carbamate (6.26 g, 92%): mp 63-64 C.; TLC Rf (5% acetone/95% CH2Cl2); 1H-NMR (DMSO-d6) delta 1.15 (s, 9H), 1.54 (s, 9H), 5.22 (s, 1H), 6.11 (s, 2H); FAB-MS m/z ((M+H)+).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3-Amino-5-tert-butylpyrazole, its application will become more common.

Reference:
Patent; Dumas, Jacques; Khire, Uday; Lowinger, Timothy B.; Paulsen, Holger; Riedl, Bernd; Scott, William J.; Smith, Roger A.; Wood, Jill; Hatoum-Mokdad, Holia; Lee, Wendy; Redman, Aniko; Johnson, Jeffrey; Sibley, Robert; US2012/46290; (2012); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics