Tag: M.W:100-200

Some common heterocyclic compound, 127107-23-7, name is 1-Methyl-1H-pyrazol-4-amine hydrochloride, molecular formula is C4H8ClN3, 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. category: pyrazoles-derivatives

Into a 25 mL round-bottom flask, were placed intermediate 44.3 (300 mg, 0.74 mmol, 1.00 equiv), 1-methyl-1H-pyrazol-4-amine hydrochloride (119 mg, 0.89 mmol, 1.20 equiv), hydrogen chloride in dioxane (0.5 mL) and n-BuOH (5 mL). The reaction was stirred for 12 h at 110 C. Upon completion of the reaction resulting mixture was concentrated under vacuum. The solution was adjusted to pH 9-10 with sodium hydroxide (2M) and resulting solids were collected by filtration. The crude product was purified by recrystallization from methanol to furnish 208.8 mg (61%) of compound 1-45 as a yellow solid. LCMS (ES, mlz): 465.4[M+H] ?H NMR (300MHz, CD3OD): 7.86 (1H, s), 7.54 (1H, s), 6.75-7.11 (1H, t), 4.05 (1H, s), 3.85 (3H, s), 3.78 (4H, t), 2.60 (4H, s), 2.08-2.32 (5H, m), 1.29-1.47 (4H, m).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 127107-23-7, its application will become more common.

Reference:
Patent; NIMBUS IRIS, INC.; ROMERO, Donna L.; MASSE, Craig E.; ROBINSON, Shaughnessy; GREENWOOD, Jeremy Robert; HARRIMAN, Geraldine; WO2015/48281; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Some common heterocyclic compound, 5334-39-4, name is 3-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. HPLC of Formula: C4H5N3O2

General procedure: Compound 30-3 and 3-bromo-2-(bromomethyl)prop-l -ene are combined with K -CO . in DMF to give compound 47-1. Compound 47-1 is combined with lithium bis(trimethylsilyl)amide to give compound 47-2, Compound 47-2 is combined with NaB in MeOH to give compound 47-3, Compound 47-3 is combined with compound 1-1, PPh3, and DIAD in THF to give compound 47-4. To compound 47- 4 in MeOH is added Pd/C, and the mixture is stirred under H2 to produce compound 47-5. Compound 47- 5, compound 5-5, and TsOH are combined in 1 ,4-dioxane to give compound D-52

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5334-39-4, its application will become more common.

Reference:
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;,
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. 96799-02-9, name is 5-(Furan-2-yl)-1H-pyrazol-3-amine, This compound has unique chemical properties. The synthetic route is as follows., Formula: C7H7N3O

Example 15To a solution of cyanuric chloride (300 mg, 1.63 mmol) in THF (16 mL) was added benzylmercaptan (0.19 mL, 1.63 mmol) and DIPEA (0.21 mL, 1.63 mmol) at 0 C. The reaction mixture was let to stir at 0 C to room temperature for 2h. 3-amino-5-(2- furyl)pyrazole (243 mg, 1.63 mmol) and DIPEA (0.21 mL, 1.63 mmol) were added to the above mixture and the resulting mixture was heated with microwave initiator at 150 C for 10 minutes. 1 -methylpiperazine (0.36 mL, 3.26 mmol) and DIPEA (0.57 mL, 3.26 mmol) were added to the mixture and the mixture was heated with microwave initiator at 60 C for 10 minutes. Saturated NaHCO3 in water was added and the mixture was extracted by ethyl acetate (3 x 50 mL). The combined organic was washed by brine, dried over sodium sulfate and concentrated. The residue was chromatographed on a silica gel column eluted with 0-5 % MeOH/DCM afforded 15 as white solid (250 mg, 34 %). 1H NMR (400 MHz, DMSOd6) delta 12.83 (s, 1H, NH), 9.92 (bs, 1Eta, NH), 7.74-6.59 (m, 9Eta, Ar-H), 4.34 (s, 2Eta, CH2), 3.75 (s, 4Eta, 2CH2), 2.34 (s, 4Eta, 2CH2), 2.29 (s, 3Eta, CH3); ESI-MS: calcd for (C22Eta24N8OS) 448, found 449 [M+H]+. HPLC: retention time: 20.34 min. purity: 99%.

According to the analysis of related databases, 96799-02-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ABRAXIS BIOSCIENCE, LLC; TAO, Chunlin; WANG, Qinwei; HO, David; NALLAN, Laxman; POLAT, Tulay; SUN, Xiaowen; DESAI, Neil; WO2010/144394; (2010); A1;,
Pyrazole – Wikipedia,
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These common heterocyclic compound, 15878-00-9, name is 4-Chloro-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. Recommanded Product: 4-Chloro-1H-pyrazole

EXAMPLE 5 7.65 g (0.075 mole) of 4-chloropyrazole were suspended in 100 ml of water and the suspension obtained first had added to it 72 g (0.64 mole) of a 50% strength aqueous KOH solution and then at 0 C. 17 g (0.15 mole) of a 30% strength aqueous hydrogen peroxide solution. After the reaction mixture had been stirred for 5 minutes, 28 g (0.18 mole) of phthalic anhydride were added in small portions at 10 C., and the whole was stirred overnight and then worked up similarly to Example 1. Yield: 7.1 g of 4-chloro-N-hydroxypyrazole, corresponding to 80% of theory.

The synthetic route of 4-Chloro-1H-pyrazole has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Basf Aktiengesellschaft; US4945167; (1990); A;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 89717-64-6, 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. 89717-64-6, name is 4-Bromo-3-nitro-1H-pyrazole belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

To a solution of 4-bromo-3- nitro-lH-pyrazole (1.5 g, 7.8 mmol) in anhydrous THF (50 mL) was added phenylboronic acid (0.95 g, 7.8 mmol), copper(II) acetate (2.1 g, 11.7 mmol) and pyridine (2.5 g, 31.2 mmol. The mixture was stirred overnight at 40C under oxygen atmosphere. After removing the insolubles by filtration, the filtrate was diluted with EtOAc (50 mL), washed with water (50 mL) and brine (50 mL), dried over a2S04, filtered and concentrated in vacuo to obtain a residue which was purified by silica gel chromatography (eluting with hexane/EtOAc = 1/1) to afford 4-bromo-3-nitro-l -phenyl- lH-pyrazole as a yellow solid (2.0 g, Yield: 95%). ESI- LCMS (m/z): 268.0 [M+l]

The synthetic route of 4-Bromo-3-nitro-1H-pyrazole has been constantly updated, and we look forward to future research findings.

Reference:
Patent; EPIZYME, INC.; CAMPBELL, John Emmerson; (178 pag.)WO2016/44666; (2016); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 5744-40-1, The chemical industry reduces the impact on the environment during synthesis 5744-40-1, name is Ethyl 1,3-dimethyl-1H-pyrazole-5-carboxylate, I believe this compound will play a more active role in future production and life.

d. Alternative synthesis of 1.S-dimethylpyrazole-delta-carboxylic acid; Ethyl-2,4-dioxovalerate (Kg) is added to a solution of methyl hydrazine (L) in ethanol (L) and heated to 6O0C for 18 hours to provide the intermediate 3,5-dimethyl-pyrazole-5- carboxylic acid ethylester.

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, Ethyl 1,3-dimethyl-1H-pyrazole-5-carboxylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; PFIZER INC.; WO2006/48761; (2006); A2;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

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 5071-61-4 as follows. SDS of cas: 5071-61-4

A solution of acid 4 (0.09 g, 0.47 mmol) in dry DMF (2 mL) treated sequentially with amine (5a-i, 6a-e and 7a-h; 0.517 mmol)and triethylamine (0.94 mmol) was stirred under a N2 atmosphere for 15 min, later TBTU (0.56 mmol) was added and reaction mixture refluxed for 4-10 h. The reaction mixture was quenched with aq satd NH4Cl solution (10 mL). After 10 min, it was diluted withCHCl3 (2 10 mL) and washed with water (10 mL), NaHCO3 solution(10 mL) and brine (10 mL). The organic layers were dried over anhydrous sodium sulfate, evaporated and the residue purified by column chromatography using 30% ethyl acetate in pet. ether to afford corresponding amides 8a-i, 9a-e and 10a-h.

According to the analysis of related databases, 5071-61-4, the application of this compound in the production field has become more and more popular.

Reference:
Article; Doma, Anuradha; Kulkarni, Ravindra; Palakodety, Radhakrishna; Sastry, G. Narahari; Sridhara, Janardhan; Garlapati, Achaiah; Bioorganic and Medicinal Chemistry; vol. 22; 21; (2014); p. 6209 – 6219;,
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. 400877-57-8, name is Methyl 1-methyl-4-nitro-1H-pyrazole-3-carboxylate, This compound has unique chemical properties. The synthetic route is as follows., name: Methyl 1-methyl-4-nitro-1H-pyrazole-3-carboxylate

To a solution of methyl 1-methyl-4-nitro-pyrazole-3-carboxylate (2 g, 10.8 mmol, CAS400877-57-8) in MeOH (20 mL) was added Pd/C (200 mg, 10% wt) under N2 atmosphere. The suspension was degassed and purged with H2 gas 3 times. The mixture was stirred under H2 (15 Psi) at rt for 12 hr. On completion, the reaction mixture was filtered and concentrated in vacuo to give the title compound (1.68 g, 100% yield) as a white solid. 1H NMR (400 MHz, CDCl3) delta 6.95 (s, 1H), 3.92 (s, 3H), 3.86 (s, 3H).

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 400877-57-8.

Reference:
Patent; Kymera Therapeutics, Inc.; Mainolfi, Nello; Ji, Nan; Kluge, Arthur F.; Weiss, Matthew M.; Zhang, Yi; (1443 pag.)US2019/192668; (2019); 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. 89088-55-1, name is 5-Bromo-1-methyl-1H-pyrazol-3-amine, A new synthetic method of this compound is introduced below., HPLC of Formula: C4H6BrN3

To a solution of 5-bromo-i-methyl-1H-pyrazol-3-amine (129 mg, 734.7 umol), 2- [3-(trifluoromethyl)phenyl]acetic acid (150 mg, 734.7 umo) in pyridine (2.0 mL) added EDCI (211 mg, 1.1 mmol). The mixture was stirred at 45C for 12 h. The reaction mixture was quenched by addition H20 (5.0 mL), extracted with dichloromethane 15.0 mL (5.0 mL x 3). The combined organic layers were washed with brine 15.0 mL (5 mL x 3), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by prep-TLC (Si02, Petroleum ether / Ethyl acetate = i/i) to afford N-(5-bromo-i-methyl-1H- pyrazol-3 -yl)-2-(3 -(trifluoromethyl)phenyl)acetamide (150 mg, crude).

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; QUENTIS THERAPEUTICS, INC.; VACCA, Joseph P.; LI, Dansu; BETTIGOLE, Sarah; (143 pag.)WO2018/222917; (2018); 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. 14521-80-3, name is 3-Bromo-1H-pyrazole belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below. Recommanded Product: 14521-80-3

Compound 1: 2-(3-(cyclopropylsulfonyl)-1H-pyrazol-1-yl)-N-(5-methoxythiazolo[5,4-b]pyridin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide 3-bromo-1H-pyrazole (1.0 g, 6.8 mmole), NiBr (0.148 g, 0.68 mmole), 2,2′-bipyridine (0.106 g, 0.68 mmole), Zinc dust (0.993 g, 13.6 mmole) and 1,2-dicyclopropyldisulfane (0.993 g, 6.8 mmole) were added to a solution of DMF (20 mL) and the mixture was heated under N2 for 18 h at 80 C. The solvent was removed from the crude reaction mixture under vacuum and the orange gum was treated with MeOH. The resulting ppt was filtered and discarded. Purification of the filtrate with preparative scale HPLC afforded compound 1A as light brown oil (367 mg). [M+H] calc’d for C6H9N2S, 141.04; found 141.0. 1H NMR (400 MHz, CHLOROFORM-d) delta ppm 0.73 (q, J=5.05 Hz, 2H) 1.02-1.17 (m, 2H) 2.26 (ddd, J=7.58, 3.66, 3.41 Hz, 1H) 6.48 (br. s., 1H) 7.82 (br. s., 1H).3-(cyclopropylthio)-1H-pyrazole (1A) (0.083 g, 0.6 mmole) was dissolved in NMP (2 mL) and the solution was chilled to 0 C. NaH (0.060 g, 1.8 mmole) was added and when the reaction subsided methyl 2-bromo-3-(tetrahydro-2H-pyran-4-yl)propanoate (0.060 g, 1.8 mmole) was introduced, and the reaction was heated at 80 C. for 1 h. The reaction was cooled and quenched with a small volume of MeOH and the crude mixture was purified using preparative scale HPLC. Compound 1B as well as a small amount of the carboxylic acid of 1B were collected. Removal of the solvent and treatment of the acid with TMSCH2N2 followed by combination with 1B afforded title compound as oil (81 mg). [M+H] calc’d for C15H23N2O3S (1B ester), 311.14; found 311.0; [M+H] calc’d for C14H21N2O3S (1B acid), 297.12; found 297.0.Compound 1B used directly from the preceding step was treated with Oxone (0.147 g, 0.24 mmole) in a 1:1 solution of THF/H2O (10 mL). After oxidation was judged complete the solvent was removed and the residue was portioned between EtOAc and H2O. The organic layer was separated, dried and concentrated to yield crude compound 1C as oil. This material was purified using preparative scale HPLC and used directly in the next step, [M+H] calc’d for C15H23N2O5S, 343.12; found 343.3.5-Methoxythiazolo[5,4-b]pyridin-2-amine (0.048 g, 0.26 mmole) was added to a microwave vial followed by DCE (2 mL). The reaction mixture was cooled to 0 C. under a N2 atmosphere. Trimethyl aluminum (2M in hexanes) (0.13 mL, 0.26 mmole) was added and when the reaction subsided the cooling bath was removed, the solution was then stirred at RT for 15 min. To this was added a solution of methyl 2-(3-(cyclopropylsulfonyl)-1H-pyrazol-1-yl)-3-(tetrahydro-2H-pyran-4-yl)propanoate 1C (0.015 g, 0.04 mmole) in DCE (2 mL) and the reaction mixture was heated in a microwave at 110 C. for 1 h. The reaction was then quenched with 1N HCl and extracted 2× with DCM. The organic layers were pooled, dried over Na2SO4; the solvent was removed and the crude residue was purified by preparative scale HPLC to afford compound 1 (46 mg). [M+H] calc’d for C21H26N5O5S2, 492.13; found 492.0. 1H NMR (400 MHz, MeOD) delta ppm 1.07 (dd, J=7.96, 2.15 Hz, 2H) 1.18-1.42 (m, 6H) 1.52 (d, J=9.35 Hz, 1H) 1.74 (d, J=2.02 Hz, 1H) 2.14 (t, J=6.32 Hz, 1H) 2.32 (t, J=10.48 Hz, 1H) 2.61-2.80 (m, 1 H) 3.29 (m, 1H, under MeOD signal) 3.79-3.98 (m, 5H) 5.50 (ddd, J=10.80, 5.68, 5.49 Hz, 1H) 6.81-6.90 (m, 2H) 7.94 (d, J=8.84 Hz, 1H) 8.10 (d, J=2.53 Hz, 1H)

The synthetic route of 14521-80-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; TAKEDA SAN DIEGO, INC.; US2009/286800; (2009); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics