Category: pyrazoles-derivatives

Synthetic Route of 128694-63-3, In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 128694-63-3 as follows.

Example 310 Production of N-[5-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)-2-fluorophenyl]-1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide In the same manner as in Example 259 and using 1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid (150 mg, 0.79 mmol), tetrahydrofuran (5 mL), N,N-dimethylformamide (1 drop), oxalyl chloride (140 muL, 1.6 mmol), N-[6-(3-amino-4-fluorophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (200 mg, 0.61 mmol) and N,N-dimethylacetamide (7 mL) as starting materials, the title compound (240 mg, 77%) was obtained as a white solid. 1H-NMR (DMSO-d6, 300 MHz) delta 0.71-0.85 (4H, m), 1.85-1.97 (1H, m), 4.15 (3H, s), 7.09 (1H, d, J=9.4 Hz), 7.21-7.28 (1H, m), 7.39-7.47 (1H, m), 7.54 (1H, s), 7.58 (1H, dd, J=6.3, 2.9 Hz), 7.95 (1H, s), 8.05 (1H, d, J=9.4 Hz), 10.45 (1H, s), 11.08 (1H, s).

According to the analysis of related databases, 128694-63-3, the application of this compound in the production field has become more and more popular.

Application of 29004-73-7, 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. 29004-73-7, name is (3-methyl-1H-pyrazol-5-yl)methanol belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

To (+/-)-6′-methanesulfonyloxy-6-(3-methanesulfonyloxypropoxy)-4,4,4′,4′,7,7′-hexa-methyl-2,2′-spirobichroman (Ex. 4a, 2 g, 3.4 mmol) and (5-methyl-1H-pyrazol-3-yl)-methanol (0.77 g, 6.8 mmol) in 50 mL of DMF at room temperature was added sodium hydride (0.41 g, 10.3 mmol, 60% dispersion in mineral oil) portion-wise. This reaction mixture was stirred at room temperature for 2 h and poured into water. The precipitate was isolated by filtration and re-dissolved in 60 mL of MeOH/THF (1:1 v/v). To this solution was added 5 mL of 5 N NaOH and the resulting mixture was stirred at 70 C. overnight. The reaction mixture was acidified with 3 N HCl to pH=6 and concentrated to 25 mL. This mixture was extracted with dichloromethane and the combined organic extracts were washed with brine and water. Purification by silica gel chromatography (EtOAc/Hexane, 1:2) afforded two products. The slower eluting component gave 0.22 g of the title compound as a white solid, mp 217-219 C. 1H NMR (CDCl3): delta 6.73 (s, 1H), 6.67 (s, 1H), 6.47 (s, 1H), 6.45 (s, 1H), 5.99 (s, 1H), 4.64 (d, 2H, J=5.2 Hz), 4.46 (s, 1H), 4.22 (t, 2H, J=7.3 Hz), 3.93-3.88 (m, 2H), 2.32-2.27 (m, 2H), 2.23 (s, 3H), 2.10 (s, 6H), 2.06-1.89 (m, 4H), 1.56 (s, 6H), 1.31 (s, 6H). HRMS (EI) Calcd for C31H40N2O5: 520.2937 (M+); found: 520.2932.; Example 18 (+/-)-6′-Hydroxy-6-[3-(5-hydroxymethyl-3-methyl-1H-pyrazol-1-yl)propoxy]-4,4,4′,4′,7,7′-hexamethyl-2,2′-spirobichromanTo (+/-)-6′-methanesulfonyloxy-6-(3-methanesulfonyloxypropoxy)-4,4,4′,4′,7,7′-hexa-methyl-2,2′-spirobichroman (Ex. 4a, 2 g, 3.4 mmol) and (5-methyl-1H-pyrazol-3-yl)-methanol (0.77 g, 6.8 mmol) in 50 mL of DMF at room temperature was added sodium hydride (0.41 g, 10.3 mmol, 60% dispersion in mineral oil) portion-wise. This reaction mixture was stirred at room temperature for 2 h and poured into water. The precipitate was isolated by filtration and re-dissolved in 60 mL of MeOH/THF (1:1 v/v). To this solution was added 5 mL of 5 N NaOH and the resulting mixture was stirred at 70 C. overnight. The reaction mixture was acidified with 3 N HCl to pH=6 and concentrated to 25 mL. This mixture was extracted with dichloromethane and the combined organic extracts were washed with brine and water. Purification by silica gel chromatography (EtOAc/Hexane, 1:2) afforded two products. The faster eluting component gave 0.095 g of the title compound as a white solid, mp 208-210 C. 1H NMR (CDCl3): delta 6.73 (s, 1H), 6.67 (s, 1H), 6.46 (s, 1H), 6.44 (s, 1H), 5.99 (s, 1H), 4.72-4.80 (br, 1H), 4.60 (s, 2H), 4.31 (t, 2H, J=7.2 Hz), 3.92 (t, 2H, J=5.1 Hz), 2.36-2.29 (m, 2H), 2.26 (s, 3H), 2.10 (s, 3H), 2.09 (s, 3H), 2.06-1.87 (m, 4H), 1.56 (s, 6H), 1.30 (s, 6H). HRMS (EI) Calcd for C31H40N2O5: 520.2937 (M+); found: 520.2940.

The synthetic route of (3-methyl-1H-pyrazol-5-yl)methanol has been constantly updated, and we look forward to future research findings.

Electric Literature of 575452-22-1, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 575452-22-1 name is 1-(1-Ethoxyethyl)-4-iodo-1H-pyrazole, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

General procedure: To dry tetrahydrofurane (for 0.019 mol of starting material 40 mL of tetrahydrofurane was used),2.5 M n-BuLi solution in n-hexane (1.1 equiv.) was added dropwise under argon atmosphere at -78C temperature, following by addition of diisopropylamine (1.2 equiv.) at -78 C degree and left tostir at same temperature for 30 min. Then pyrazole 2a, 3a or 5a (1 equiv.) solution intetrahydrofurane (for 0,019 mol of protected pyrazole – 5 mL of THF were used) was added to thereaction mixture at -78 C temperature and left to stir at the same temperature for additional 30 min.Then dimethylformamide (1.3 equiv.) solution in tetrahydrofurane (for 0.025 mol ofdimethylformamide – 5 mL of THF were used) were added dropwise at -78 C degree and left towarm to room temperature overnight. Reaction mixture was cooled down to 5 C temperature andquenched with saturated NH4Cl solution in deionized water (for 0.019 mol of starting material – 12mL of saturated NH4Cl solution were used). Organic layer was separated, inorganic layer wasextracted with dichloromethane (3×10 mL). Organic layers were combined and washed withdeionized water (2×10 mL), dried with anhydrous Na2SO4 and evaporated under reduced pressure.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1-(1-Ethoxyethyl)-4-iodo-1H-pyrazole, and friends who are interested can also refer to it.

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. 4331-28-6, name is 1H-Pyrazol-4-amine hydrochloride, A new synthetic method of this compound is introduced below., category: pyrazoles-derivatives

To a mixture of (R)-2-(methylcarbamoyl)-6-(1-phenylethyl)isonicotinic acid (53.7 mg, 0.19 mmol),HATU (86.7 mg, 0.23 mmol) and 1H-pyrazol-4-amine, hydrochloride (28.9 mg, 0.24 mmol) in DMF (1mL) was added DIPEA (0.132 mL, 0.76 mmol). The resulting dark grey solution was stirred at rt for2.75 h. The reaction mixture was diluted with DMSO (2 mL) and directly purified by MDAP (3 mLinjection, high pH). The required fractions (fractions 1 and 2) were combined and evaporated in vacuoto give the desired product as a light yellow solid – (R)-N2-methyl-6-(1-phenylethyl)-N4-(1H-pyrazol-4-yl)pyridine-2,4-dicarboxamide (39.9 mg, 0.11 mmol, 61 % yield)LCMS (2 mm High pH): Rt = 0.92 mi [MH]+ = 350.3.

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 of 796729-03-8, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 796729-03-8 name is 5,6-Dihydro-4H-pyrrolo[1,2-b]pyrazole-2-carboxylic acid, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

Step (e) ((ls,4s)-4-(2-(4′-(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 suspension of N-((ls,4s)-4-aminocyclohexyl)-2-(4′-(3-((3S,5R)-3,5-dimethylpiperazin-l- yl)propyl)biphenyl-3-yloxy)-5-fluoronicotinamide (150 mg, 0.24 mmol) in acetonitrile (4 mL) was added 5,6-dihydro-4H-pyrrolo[l,2-b]pyrazole-2-carboxylic acid (36.1 mg, 0.24 mmol) and triethylamine (0.330 niL, 2.37 mmol). 1-Propanephosphonic acid cyclic anhydride, 1.57M solution in THF (0.159 mL, 0.25 mmol) was then added and the mixture stirred at RT for 2 hours. The mixture was evaporated to dryness and the residue dissolved in DCM (100 ml) and washed with saturated NaHCO3 (aq), brine, dried (MgSO4) and evaporated to give a foam. This was purified by HPLC to give the title compound as a white solid. Yield: 95 mg1H NMR (400 MHz, CD3OD) delta 8.45 (d, J = 7.4 Hz, IH), 8.12 (d, J = 3.1 Hz, IH), 8.08 – 8.04 (m, IH), 7.52 (d, J = 8.2 Hz, 2H), 7.48 – 7.45 (m, 2H), 7.40 – 7.37 (m, IH), 7.25 (d, J = 8.2 Hz, 2H), 7.17 – 7.11 (m, IH), 6.39 (s, IH), 4.15 – 4.07 (m, IH), 4.04 (t, J = 7.3 Hz, 2H), 3.98 – 3.91 (m, IH), 3.58 – 3.47 (m, 4H), 2.94 – 2.83 (m, 4H), 2.71 (t, J = 7.1 Hz, 2H), 2.64 – 2.52 (m, 4H), 2.06 – 1.93 (m, 2H), 1.89 – 1.76 (m, 6H), 1.74 – 1.63 (m, 2H), 1.33 (d, J = 6.2 Hz, 6H). MS: [M+H]+=694 (calc=694) (MultiMode+)

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5,6-Dihydro-4H-pyrrolo[1,2-b]pyrazole-2-carboxylic acid, and friends who are interested can also refer to it.

Synthetic Route of 138907-73-0, 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. 138907-73-0, name is Ethyl 1-(4-fluorophenyl)-1H-pyrazole-4-carboxylate belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

[1-(4-Fluorophenyl)-1 H-pyrazol-4-yl]acetic acid was prepared from ethyl 1-(4- fluorophenyl)-1 H-pyrazole-4-carboxylate by the procedure outlined in Scheme 5 and using analogous methodology to that described in J. Heterocyclic Chem., 30, 997 (1993).

The synthetic route of Ethyl 1-(4-fluorophenyl)-1H-pyrazole-4-carboxylate has been constantly updated, and we look forward to future research findings.

Reference of 1001020-13-8, The chemical industry reduces the impact on the environment during synthesis 1001020-13-8, name is (3-Trifluoromethyl-1H-pyrazol-4-yl)methanol, I believe this compound will play a more active role in future production and life.

(3-(Trifluoromethyl)-1H-pyrazol-4-yl)methanol (54.00 g, 0.325 mol) was suspended in toluene (2 L). MnO2 (113.00 g, 1.30 mol) and 4 molecular sieve powder (54.00 g) were added. The reaction mixture was stirred at reflux under nitrogen with a Dean-Stark trap for 5.5 h. The resulting mixture was filtered hot and the cake allowed to cool before washing with 1:1 DCM:MeOH solution (3×500 mL). The combined filtrates were concentrated in vacuo to give the desired product (54.00 g, 0.329 mol, 100%).1H NMR (400 MHz, DMSO): delta 8.72 (s, 1H), 9.91 (s, 1H)

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-Trifluoromethyl-1H-pyrazol-4-yl)methanol, other downstream synthetic routes, hurry up and to see.

Some common heterocyclic compound, 96450-53-2, name is 1-(2-Chloroethyl)-1H-pyrazole, molecular formula is C5H7ClN2, 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. name: 1-(2-Chloroethyl)-1H-pyrazole

A mixture of 13.02 g (0.1 mol) of 1-(2-chloroethyl)pyrazole 1, 11.2 g (0.2 mol) of KOH, and 50 mL of 50 wt% aqueous solution of MMO was vigorously stirred during 2 h at 80C. After cooling to ambient, the reaction mixture was extracted with chloroform. The solvent was removed, and the residue was distilled in vacuum. Yield 7.0 g (75%), bp 63C(50 mmHg), nD20 1.5160 [16]. IR spectrum, nu, cm-1:1520 (ring), 1640 (C=C). 1H NMR spectrum, delta, ppm(J, Hz): 5.00 d.d (1H, =CH2, J = 9.0, 1.5), 5.52 d.d(1H, =CH2, J = 15.8, 1.5), 6.26 t (1H, 4-H, J = 2.2),7.12 d.d (1H, NC=H, J = 15.8, 9.0), 7.50 d (1H, 3-H,J = 2.4), 7.58 d (1H, 5-H, J = 2.0).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 96450-53-2, its application will become more common.

25700-12-3, name is 3-(1H-Pyrazol-1-yl)pyridine, 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. name: 3-(1H-Pyrazol-1-yl)pyridine

Step 1: 3-(4-Bromopyrazol-1-yl)pyridine 3-Pyrazol-1-ylpyridine (500 mg, 3.44 mmol) was dissolved in acetonitrile (15 ml), and ammonium cerium(IV) nitrate (944 mg, 1.72 mmol) was added (slightly exothermic). N-Bromosuccinimide (736 mg, 4.13 mmol) was added a little at a time (slightly exothermic) and the mixture was stirred at room temperature for 30 min and then heated under reflux for 3 hours (h). After the mixture had cooled, ethyl acetate was added. The organic phase was washed with water, washed with a sodium sulphate solution and then dried with magnesium sulphate. The solvent was removed under reduced pressure using a rotary evaporator. Yield: 750 mg (93% of theory), logP(HCOOH) 1.56, [M++1] 224.0 1H-NMR (d6-DMSO): 7.54 (m, 1H), 7.90 (s, 1H), 8.20 (m, 1H), 8.55 (m, 1H), 8.79 (s, 1H), 9.06 (m, 1H).

The synthetic route of 25700-12-3 has been constantly updated, and we look forward to future research findings.

Electric Literature of 1001020-17-2,Some common heterocyclic compound, 1001020-17-2, name is 3-(tert-Butyl)-1H-pyrazole-4-carbaldehyde, molecular formula is C8H12N2O, 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 842-(2-(3-rert-butyl-4-formyl-1H-pyrazol-1-vhacetamido)-N-(2-hvdroxyethvn-4.5.6.7- tetrahvdrobenzofbithiophene-3-carboxamide 2-(2-Bromoacetamido)-N-(2-hydroxyethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3- carboxamide (1.66 g, 4.60 mmol), 3-tert-butyl-1 H-pyrazole-4-carbaldehyde (1.75 g, 11.49 mmol) and potassium carbonate (2.54 g, 18.38 mmol) were mixed with DMF (20 ml_) and heated at 70 CC for 2 h. On cooling, the reaction was partitioned between EtOAc and water. The organics were washed with brine, dried over MgSO4 and concentrated directly onto silica for chromatographic purification (0-100 % EtOAc/heptane). Concentration in vacuo yielded a white solid (1.64 g, 3.79 mmol, 83 %). MS (ESI): m/z 433.5 [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-(tert-Butyl)-1H-pyrazole-4-carbaldehyde, its application will become more common.