Day: May 13, 2021

Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 90253-21-7, name is 4-Cyclopropyl-1H-pyrazole, A new synthetic method of this compound is introduced below., name: 4-Cyclopropyl-1H-pyrazole

A mixture of 3-iodo-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (Example 18, step 1, 163 mg, 0.54 mmol), 4-cyclopropyl-1H-pyrazole (116 mg, 1.1 mmol), K2CO3(s) (149 mg, 1.1 mmol), copper (I) iodide (21 mg, 0.11 mmol), and (1R,2R)-N1,N2-dimethylcyclohexane-1,2- diamine (43 muL, 0.27 mmol) in DMF (5.38 mL) was sparged with Ar(g) and stirred at 110C until completion as determined by chromatographic (TLC or LC) monitoring. The resulting mixture was purified with silica chromatography (0 to 20% MeOH in DCM) to afford the title compound (115 mg, 75.5%). MS (apci) m/z = 284.1 [M+H].

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Patent; ARRAY BIOPHARMA INC.; BLAKE, James F.; DAI, Donghua; HAAS, Julia; JIANG, Yutong; KOLAKOWSKI,, Gabrielle R.; METCALF, Andrew T.; MORENO, David A.; PRIGARO, Brett; REN, Li; (330 pag.)WO2019/143991; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

1204298-65-6, name is 5-(Difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid, 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. Computed Properties of C6H6F2N2O2

To a suspension of 6-(2-amino-5-chlorothiazol-4-yl)-3,4-dihydroquinolin-2(1H)-one (0.100 g, 0.41 mmol), 5-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (0.080 g, 0.45 mmol), pyridine (0.15 mL, 1.83 mmol) in acetonitrile (4 mL) in a sealed tube was added propylphosphonic anhydride solution (50 wt % in ethyl acetate, 0.61 mL, 1.02 mmol). The sealed tube was heated to 100 C. for 16 h. After cooling, the precipitate was collected by filtration and washed with cold 1:1 acetonitrile/water to give 5-(difluoromethyl)-1-methyl-N-(4-(2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)thiazol-2-yl)-1H-pyrazole-4-carboxamide (0.119 g, 72%). 1H NMR (400 MHz, DMSO-d): delta 12.74 (bs, 1H), 10.19 (s, 1H), 8.45 (s, 1H), 7.74 (m, 1H), 7.69 (dd, 1H, J=8.4, 2.0 Hz), 7.56 (t, JHF=54 Hz, 1H), 7.53 (s, 1H), 6.90 (d, 1H, J=8.0 Hz), delta, 4.04 (s, 3H), 2.93 (t, 2H, J=7.2 Hz), 2.48 (partial masked under d-DMSO, m, 2H); MS (ESI): Calcd. for C18H15F2N5O2S: 403, found 404 (M+1)+.

The synthetic route of 1204298-65-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Nantbio, Inc.; Tao, Chunlin; Nallan, Laxman; Ho, David G.; Wang, Qinwei; Weingarten, Paul; Juncker-Jensen, Anna B.; (121 pag.)US2018/201610; (2018); A1;,
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. 796729-10-7, name is 5,6-Dihydro-4H-pyrrolo[1,2-b]pyrazole-3-carboxylic acid, This compound has unique chemical properties. The synthetic route is as follows., Safety of 5,6-Dihydro-4H-pyrrolo[1,2-b]pyrazole-3-carboxylic acid

Step 3: Synthesis of tert-butyl(5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)carbamate (CF72) CF70 (280 mg, 1.84 mmol) was mixed with tert-butanol (6 mL) and triethyl amine (0.8 mL, 4 mmol). Diphenyl phosphoryl azide (0.71 mL, 3.31 mmol) was added via a syringe and the mixture was stirred at ambient temperature for overnight. The solution was heated at reflux for 24 h. The volatile components were removed on a rotary evaporator and the residue was purified by flash column chromatography. CF72 was isolated in 224 mg. 1H NMR (300 MHz, CDCl3): 7.36 (s, 1H), 6.24 (s, 1H), 4.05 (t, J=7.31 Hz, 2H), 2.98-2.82 (m, 2H), 2.60-2.44 (m, 4H), 1.46 (s, 9H). 13C NMR (75 MHz, CDCl3): 153.76, 137.82, 137.01, 114.08, 80.10, 48.23, 28.48, 26.26, 23.63. ESI-MS calculated for C11H18N3O2 [M+H]+=224.14, Observed: 224.58.

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 796729-10-7.

Reference:
Patent; THE REGENTS OF THE UNIVERSITY OF MICHIGAN; Wang, Shaomeng; Zhao, Yujun; Zhou, Bing; Aguilar, Angelo; Liu, Liu; Bai, Longchuan; McEachern, Donna; Sun, Duxin; Wen, Bo; Luo, Ruijuan; Zhao, Ting; Chinnaiyan, Arul; Asangani, Irfan A.; Stuckey, Jeanne; Meagher, Jennifer Lynn; Ran, Xu; US2015/246923; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 3273-44-7, 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. 3273-44-7, name is 5-Methyl-1H-pyrazole-3-carbaldehyde belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

Step 1: tert-Butyl 3-formyl-5-methyl-lH-pyrazole-l-carboxylate 5-Methyl-lH-pyrazole-3-carbaldehyde (5.4 g, 49 mmol) was dissolved in acetonitrile (200 mL) and cooled to 0 C with stirring. DMAP (0.60 g, 4.9 mmol) and di-tert-butyldicarbonate (12.9 g, 59.q mmol) were added and the solution was allowed to warm to rt and stir for 16 h. The reaction was diluted with EtOAc (200 mL). Then the mixture was washed with IN HC1 (aq.) (2xl00mL), saturated aq NaHC03 (2xl00mL), dried over magnesium sulfate, filtered and concentrated. The residue was purified on silica gel to give tert-butyl 3-formyl-5-methyl-lH-pyrazole-l-carboxylate (3.9 g, 38%) as a clear oil. ‘H NMR (CDC13) delta 10.10 (s, 1H), 6.65 (s, 1H), 2.60 (s, 3H), 1.72 (s, 9H).

The synthetic route of 5-Methyl-1H-pyrazole-3-carbaldehyde has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MILLENNIUM PHARMACEUTICALS, INC.; DUFFEY, Matthew, O.; ENGLAND, Dylan, B.; HU, Zhigen; ITO, Mitsuhiro; LANGSTON, Steven, P.; MCINTYRE, Charles; MIZUTANI, Hirotake; XU, He; WO2015/2994; (2015); A2;,
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. 90253-21-7, name is 4-Cyclopropyl-1H-pyrazole, This compound has unique chemical properties. The synthetic route is as follows., name: 4-Cyclopropyl-1H-pyrazole

Preparation 23b: {3-[4-(4-cyclopropylpyrazol-1 -yl)benzyl]-4-difluoromethoxy-2-ethyl- 8-fluoroquinolin-5-yloxy}acetic acid methyl ester; A mixture of (4-{[4-difluoromethoxy-2-ethyl-8-fluoro-5-(2-methoxy-2-oxoethoxy) quinolin-3-yl]methyl}phenyl)boronic acid (0.1 g), 4-cyclopropyl-1 H-pyrazole (0.047 g), cuprous acetate (0.078 g) and pyridine (3 ml_) was heated at 40 0C for 24 hours. The mixture was cooled to room temperature, diluted with water (10 mL) and extracted with ethyl acetate. The combined extracts were washed with saturated aqueous sodium chloride solution, dried over magnesium sulphate and then concentrated under reduced pressure. Purification of the residue by column chromatography on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (1 :0 to 7:3 by volume) gave title compound as pale green oil (0.09 g).MS: ESI (+ve) (Method B): 526 (M+H)+, Retention time 4.5 min

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 90253-21-7.

Reference:
Patent; ARGENTA DISCOVERY LIMITED; WO2008/122784; (2008); A1;,
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. 3273-44-7, name is 5-Methyl-1H-pyrazole-3-carbaldehyde, This compound has unique chemical properties. The synthetic route is as follows., Computed Properties of C5H6N2O

General procedure: To a suspension of 5-methyl-1H-pyrazole-3-carbaldehyde (18; 2-6 equiv) in anhydrous THF (10 mL) (in the case of the synthesis of 1) or MeOH (in the case of the synthesis of 2-5 and 11), the corresponding derivative bearing one to three amino groups (17,21 25-289d,11 or 36,4c see Scheme 1 and Scheme 2) (1 equiv), dissolved in anhydrous MeOH (5 mL), was added. The resulting mixture was heated at reflux until a clear solution resulted and then stirred at r.t. (up to 4 days, TLC analysis). The resulting imines were reduced without further purification by addition of NaBH4 (3-9 equiv) in portions. After complete addition of the reducing agent, the reaction mixture was stirred for 24 h at r.t. and then the solvent was removed under reduced pressure. The residue was suspended in CHCl3-H2O (1:1, 10 mL) and stirred for 12 h at r.t. The resulting suspension was extracted with CHCl3 (3 ¡Á 20 mL), dried over MgSO4, and the solvent was removed. The crude product was purified by column chromatography.

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 3273-44-7.

Reference:
Article; Koch, Niklas; Seichter, Wilhelm; Mazik, Monika; Synthesis; vol. 48; 17; (2016); p. 2757 – 2767;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 139756-04-0,Some common heterocyclic compound, 139756-04-0, name is 1-Methyl-4-(2-propoxybenzamido)-3-propyl-1H-pyrazole-5-carboxamide, molecular formula is C18H24N4O3, 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.

EXAMPLE 19 1-Methyl-5-(2-n-propoxyphenyl)-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one 1-Methyl-4-(2-n-propoxybenzamido)-3-n-propylpyrazole-5-carboxamide (0.34 g, 0.99 mmol) was added to a stirred mixture of 30% hydrogen peroxide solution (1.0 ml), potassium carbonate (0.54 g, 3.92 mmol), water (10 ml) and ethanol (5 ml). The mixture was heated under reflux for 38 hours and then evaporated under vacuum. The residue was suspended in water (20 ml), then the mixture acidified with 2N hydrochloric acid and extracted with dichloromethane (3*20 ml). The extracts were combined, dried (Na2 SO4) and evaporated under vacuum. The resulting residue was chromatographed on silica gel (6 g), using a methanol in dichloromethane elution gradient (0.0-1.0%), to give an oil, successive trituration of which with ether gave the required product as a white solid (0.19 g, 59%), m.p. 111-114 C. Found: C,66.26; H,6.92; N,17.15. C18 H22 N4 O2 requires C,66.23; H,6.80; N,17.17%.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1-Methyl-4-(2-propoxybenzamido)-3-propyl-1H-pyrazole-5-carboxamide, its application will become more common.

Reference:
Patent; Pfizer Inc.; US5250534; (1993); A;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 873191-23-2, name is 5-(Bromomethyl)-1,3-dimethyl-1H-pyrazole, belongs to pyrazoles-derivatives compound, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound 873191-23-2, name: 5-(Bromomethyl)-1,3-dimethyl-1H-pyrazole

Amixture of 83mg G2 (0.25 mmol, 1.00 equiv.), 48 mg S-bromomethyl-ljS-dimethyl-l//-pyrazole (C3) (0.25 mmol, 1.00 equiv.) and 38 mg potassium carbonate (0.28 mmol, 1.10equiv.) in DMF was stirred for 44 h at room temperature then partitioned between 20mL eachwater and 3:1 diethyl etherdichloromethane. The separated aqueous layer was extracted with2x20mL 3:1 diethyl ether:dichloromethane. The combined organic extracts were washedwith 3x20mL water and 20mL brine. The organic separation was dried over magnesiumsulfate, filtered and concentrated in vacuo to afford a yellow glassy solid. The product waspurified by column chromatography on silica gel, eluting with 4% methanol indichloromethane. Purified product G3 isolated as an off-white solid, 73mg.

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; AMGEN SF, LLC; WO2006/4925; (2006); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 25700-12-3, name is 3-(1H-Pyrazol-1-yl)pyridine, belongs to pyrazoles-derivatives compound, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound 25700-12-3, Formula: C8H7N3

Step 2: Preparation of 3-(4-nitro-pyrazol-1-yl)-pyridine 3-Pyrazol-1-yl-pyridine (2 g, 0.032 mol) was dissolved in concentrated H2SO4 (32 mL 0.598 mmol) and cooled to -5 C. using an ice bath. To the reaction mass, a 1:1 mixture of concentrated HNO3 (30 mL, 0.673 mmol) and concentrated H2SO4 (30 ml, 15 Vol.) was added dropwise over a period of 30 min. Cooling was discontinued and the reaction mixture was stirred at room temperature overnight. After the reaction was complete, the mixture was poured over crushed ice and neutralized with saturated NaHCO3, filtered, washed with water and dried to furnish the nitro pyrazole as pale yellow solid (1.8 g, 68%): 1H NMR (400 MHz, DMSO-d6) delta 9.03 (d, J=2.8 Hz, 1H); 8.70 (dd, J=4.8, 1.6 Hz, 1H), 8.69 (s, 1H), 8.33 (s, 1H), 8.11-8.08 (m, 1H), 7.51 (dd, J=8.4, 4.8 Hz, 1H); MS (m/z) 191 [M+1].

In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles, 3-(1H-Pyrazol-1-yl)pyridine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Yap, Maurice C.H.; Buysse, Ann M.; Knueppel, Daniel; Zhang, Yu; Garizi, Negar; Niyaz, Noormohamed M.; Lowe, Christian T.; Hunter, Ricky; Trullinger, Tony K.; Demeter, David A.; Pernich, Dan; Deamicis, Carl; Ross, JR., Ronald; Johnson, Timothy C.; US2012/110702; (2012); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 796729-03-8, name is 5,6-Dihydro-4H-pyrrolo[1,2-b]pyrazole-2-carboxylic acid, A new synthetic method of this compound is introduced below., HPLC of Formula: C7H8N2O2

Step (c) N-((ls,4s)-4-(2-(3′-(3-((3S,5R)-3,5-Dimethylpiperazin-l-yl)propyl)biphenyl-3- yloxy)-5-fluoronicotinamido)cyclohexyl)-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazole-2- carboxamideTo a stirred solution of N-((ls,4s)-4-aminocyclohexyl)-2-(3′-(3-((3S,5R)-3,5- dimethylpiperazin- 1 -yl)propyl)biphenyl-3-yloxy)-5-fluoronicotinamide hydrochloride (0.180 g, 0.28 mmol) in acetonitrile (2 mL) was added 5,6-dihydro-4H-pyrrolo[l,2-b]pyrazole-2- carboxylic acid (0.052 g, 0.34 mmol) and triethylamine (0.397 mL, 2.85 mmol). The reaction mixture was stirred at RT for 10 min. 1-Propanephosphonic acid cyclic anhydride, 1.57M solution in THF (0.228 mL, 0.34 mmol) was added and the reaction mixture was stirred at RT under nitrogen for 2 h then concentrated to give crude product. The crude product was purified by preparative HPLC on a Waters X-Bridge column using a 70-20% gradient of aqueous 0.2% TFA in methanol as eluent. The fractions containing the desired compound were evaporated to dryness to afford the title compound as a white solid. Yield: 14 mg 1H NMR (400 MHz, CD3OD) delta 8.05 (s, IH), 8.01 (d, J= 8.3 Hz, IH), 7.42 (s, 2H), 7.38 – 7.32 (m, 3H), 7.27 – 7.23 (m, IH), 7.16 – 7.06 (m, 2H), 6.30 (s, IH), 4.08 – 4.02 (m, IH), 3.95 – 3.91 (m, 2H), 3.88 – 3.69 (m, 3H), 3.06 – 2.94 (m, 2H), 2.80 – 2.75 (m, 2H), 2.69 – 2.58 (m, 2H), 2.54 – 2.44 (m, 2H), 2.10 – 1.95 (m, 2H), 1.84 – 1.65 (m, 6H), 1.64 – 1.52 (m, 4H), 1.40 – 1.25 (m, 6H), 0.97 – 0.90 (m, IH). [M+H]+=694 (calc=694) (MultiMode+)

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2009/144494; (2009); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics