Tag: M.W:200-300

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. 866837-96-9, name is Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate, A new synthetic method of this compound is introduced below., Recommanded Product: 866837-96-9

To a solution of ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate (498 mg) synthesized according to the method described in WO2004/98589 in N,N-dimethylacetamide (10 mL) were added N-ethyldiisopropylamine (417 mg) and benzoyl chloride (453 mg) at room temperature. After stirring at the same temperature for 18 hr, water was added and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=6:1?3:1) to give the title compound as colorless crystals (yield 550 mg, yield 76%). 1H-NMR(CDCl3)delta:1.42(3H,t,J=7.2Hz), 4.44(2H,q,J=7.2Hz), 7.36(1H,s), 7.43-7.59(8H,m), 7.69-7.73(2H,m), 7.95(1H,brs).

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; Takeda Pharmaceutical Company Limited; EP2196459; (2010); 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. 16078-71-0, name is Ethyl 5-amino-1-phenyl-1H-pyrazole-4-carboxylate, This compound has unique chemical properties. The synthetic route is as follows., Formula: C12H13N3O2

B. 5-Bromo-1-phenyl-1H-pyrazole-4-carboxylic acid, ethyl ester To a solution of 20.0 g of 5-amino-1-phenyl-1H-pyrazole-4-carboxylic acid, ethyl ester and 10 ml of bromine in 200 ml of chloroform was added 15.8 g of isoamyl nitrite dropwise. The reaction mixture was allowed to stir at room temperature for about 24 hours and the volatiles were removed under reduced pressure. The residue was recrystallized from ethanol/water to provide 10.0 g of 5-bromo-1-phenyl-1H-pyrazole-4-carboxylic acid, ethyl ester. Yield 38%. mp=86-89 C.

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 16078-71-0.

Reference:
Patent; Eli Lilly and Company; US4620865; (1986); A;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

These common heterocyclic compound, 706819-66-1, name is 2-Bromo-1-(1-methyl-1H-pyrazol-4-yl)ethanone, 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. Safety of 2-Bromo-1-(1-methyl-1H-pyrazol-4-yl)ethanone

2-Bromo-1 -(1 -methyl-1 H-pyrazol-4-yl)-ethanone (CAS 706819-66-1) (820 mg; 4.04 mmol) was added to a mixture of intermediate 2 (1 g; 3.36 mmol) and K2C03 (930 mg; 6.73 mmol) in DMF (20 mL). The reaction mixture was heated at 65C for 18 hours. The reaction mixture was cooled to room temperature, poured onto water and extracted with EtOAc. The organic layer was decanted, washed with brine, dried over MgS04, filtered and evaporated to dryness. The residue was purified by chromatography over silica gel (irregular SiOH 40g; mobile phase: 95% DCM, 5% MeOH, 0.5% NH4OH). The pure fractions were collected and evaporated to dryness, yielding 345 mg (25%) of intermediate 3. 1H NMR (500 MHz, DMSO-d6) delta 9.78 (s, 1 H), 9.27 (s, 1 H), 9.09 (s, 1 H), 8.71 (s, 1 H), 8.31 (s, H), 7.01 (t, J = 7.88 Hz, 1 H), 3.79 – 4.05 (m, 9H); MS (ESI+) m/z (%) (r.t. 2.34) 400 (100) [M+H]+, 799 (95) [2M+H]+ (method B1 ). MP. : 224C (Kofler).

The synthetic route of 2-Bromo-1-(1-methyl-1H-pyrazol-4-yl)ethanone has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTEX THERAPEUTICS LIMITED; SAXTY, Gordon; HAMLETT, Christopher Charles Frederick; BERDINI, Valerio; MURRAY, Christoper William; ANGIBAUD, Patrick Rene; QUEROLLE, Olivier Alexis Georges; PONCELET, Virginie Sophie; WO2013/179033; (2013); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

These common heterocyclic compound, 398495-65-3, name is 5-tert-Butyl 1-ethyl 3-aminopyrrolo[3,4-c]pyrazole-1,5(4H,6H)-dicarboxylate, 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: 398495-65-3

General procedure: To a solution of 2 (13.00 g, 43.90 mmol) and DIEA ( 33.60 g, 260.00 mmol) in dry THF (400 mL) was added dropwise a solution of corresponding acyl chlorides (48.30 mmol) in dry THF (50 mL) over a period of 1 h at room temperature. The reaction mixture was stirred for 12 h at the same temperature and concentrated under reduced pressure. The residue was treated with ethyl acetate / saturated saline (400 mL: 400 mL) and stayed for 2 h, and then filtered. The precipitate was washed with diethyl ether (30 mL), and dried in vacuo to yield the title compounds 3a-d. 3e was obtained by flash chromatography (180 g silica gel, petroleum ether/AcOEt, 0-30%, V/V).

The synthetic route of 5-tert-Butyl 1-ethyl 3-aminopyrrolo[3,4-c]pyrazole-1,5(4H,6H)-dicarboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Article; Bai, Xiao-Guang; Yu, Dong-Ke; Wang, Ju-Xian; Zhang, Hao; He, Hong-Wei; Shao, Rong-Guang; Wang, Yu-Cheng; Li, Xue-Mei; Bioorganic and medicinal chemistry letters; vol. 22; 22; (2012); p. 6947 – 6951,5;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Some common heterocyclic compound, 83-10-3, name is 1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid, molecular formula is C12H12N2O3, 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: 83-10-3

Step 4) 4-(4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamido)-2,5-difluorophenoxy)picolinamide To a solution of 4-(4-amino-2,5-difluorophenoxy)picolinamide (200 mg, 0.76 mmol), and 1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid (165 mg, 0.75 mmol) in DCM (10 mL) was added EDCI (175 mg, 0.93 mmol), and HOAT (26 mg, 0.15 mmol). The reaction was stirred at 45 C. for 16 hours, cooled to rt and diluted with EtOAc (20 mL). The solid was collected through filtration, dried at 45 C. in vacuo overnight to give the title compound as a white solid (230 mg, 63.7%). MS (ESI, pos. ion) m/z: 480.1 [M+H]+; 1H NMR (400 MHz, DMSO-d6): delta (ppm) 11.24 (s,1H), 8.53-8.57 (m, 2H), 8.15 (s, 1H), 7.75 (s, 1H), 7.53-7.59 (m, 4H), 7.44-7.45 (m, 3H), 7.24-7.25 (d, J=5.2 Hz, 1H), 3.43 (s, 3H), 2.70 (s, 3H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 83-10-3, its application will become more common.

Reference:
Patent; Sunshine Lake Pharma Co., Ltd.; Calitor Sciences, LLC; Xi, Ning; Wu, Yanjun; Liao, Min; Feng, Yanming; US2015/37280; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

These common heterocyclic compound, 398491-61-7, name is tert-Butyl 3-amino-6,6-dimethylpyrrolo[3,4-c]pyrazole-5(1H,4H,6H)-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. category: pyrazoles-derivatives

Example 2: 3-[(2-chlorothieno[3,2-d]pyrimidin-4-yl)amino]-6,6-dimethyl-Lambda/-[trans-2- phenylcyclopropyl]-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1W)-carboxamide.2a 2Preparation of Compound 2a: rert-butyl-3-[(2-chlorothieno[3,2-cdpyrimidin-4-yl)amino]-6,6- dimethyl-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxylate.; To a stirring solution of ferf-butyl 3-amino-6,6-dimethyl-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1/7)- carboxylate (2.4g, 9.5 mmol) in DMA (1OmL) was added 2,4-dichlorothieno[3,2-c/]pyrimidine(2.05g, 1.05eq) and triethylamine (2.64ml, 2eq). The resulting mixture was heated to 1500C for 5 minutes in microwave reactor. Saturated NaHCO3 was added and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate, concentrated in vacuo. The residue was washed with methylene chloride. Compound 2a (2.71 g, 68%) was obtained as a brown solid and directly carried onto the next without further purification. LCMS (API-ES, M+H+): 421. To a stirring mixture of compound 2a(0.102g, 0.24mmol) in CH2CI2 (2ml), was added TFA (2ml). The resulting mixture was stirred at room temperature for 2h. After the reaction mixture was concentrated in vacuo, a solution of TEA (135ul, 4eq) in MeCN (1ml) CH2CI2 (1ml) was added and followed by trans-2- phenylcyclopropyl isocyanate. The resulting mixture was stirred at room temperature for 1h. The reaction mixture was purified by prep-HPLC to provide compound 2 as a white solid (0.021 g, 18%). 1H NMR (CD3OD) delta: 1.04 – 1.12 (m, 2 H), 1.69 (d, J=3.28 Hz, 2 H), 1.95 (m, 1 H), 2.67 – 2.73 (m, 1 H), 4.48 (s, 2 H), 7.01 – 7.06 (m, 3 H), 7.11 – 7.17 (m, 2 H), 7.25 (d, J=5.31 Hz, 1 H), 8.05 (d, J=4.55 Hz, 1 H). Anal. (C^H^NyOSCI.OLambdaHOAc.O^HaO) C, H, N. HPLC: >95% purity.

The synthetic route of tert-Butyl 3-amino-6,6-dimethylpyrrolo[3,4-c]pyrazole-5(1H,4H,6H)-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PFIZER INC.; WO2006/72831; (2006); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 84547-86-4, name is 4-Bromo-1-methyl-1H-pyrazole-3-carboxylic acid, 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 84547-86-4, name: 4-Bromo-1-methyl-1H-pyrazole-3-carboxylic acid

Example 39 4-{3-[(1S)-1-(2-Chloro-3-fluoro-6-methoxyphenyl)ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-1-methyl-1H-pyrazole-3-carboxamide A mixture of 4-bromo-1-methyl-1H-pyrazole-3-carboxylic acid (20.0 mg, 0.0976 mmol), NH4Cl (52.2 mg, 0.976 mmol), TBTU (62.6 mg, 0.195 mmol), DIPEA (0.0340 mL, 0.195 mmol) and DMF (2 mL, 20 mmol) was stirred at rt for 10 min. The material was extracted with EtOAc, and washed with sat. NaHCO3 (3*) to remove carboxylic acid starting material. The organic layer was concentrated in vacuo. 3-[(S)-1-(2-Chloro-3-fluoro-6-methoxyphenyl)-ethyl]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (15.0 mg, 0.0348 mmol), (1,1’bis-(diphenylphosphino)-ferrocene) palladium dichloride (3.57 mg, 0.00488 mmol), K2CO3 (20.2 mg, 0.146 mmol) and 4:1 dioxane:H2O (1 mL, 10 mmol) were added, and the mixture was heated to 95 C. for 30 min. The solution was used directly for HPLC purification, and the fractions containing the pure product were concentrated in vacuo to afford the title compound as a white solid. 1H NMR (400 MHz, CD3OD): delta=1.80 (d, J=7.1 Hz, 3H), 3.70 (br. s., 3H), 3.96 (s, 3H), 5.14 (q, J=7.2 Hz, 1H), 6.88 (dd, J=9.2, 4.2 Hz, 1H), 7.05 (t, J=8.8 Hz, 1H), 7.30 (d, J=1.0 Hz, 1H), 7.66 (s, 1H), 7.72 (s, 1H), 8.22 (br. s., 1H). MS (ES+): m/z=428.11/430.12 (100/50) [MH+]. HPLC: tR=1.33 min (polar-3 min, UPLC-ACQUITY).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 4-Bromo-1-methyl-1H-pyrazole-3-carboxylic acid, and friends who are interested can also refer to it.

Reference:
Patent; OSI Pharmaceuticals, LLC; US2011/281888; (2011); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 50877-42-4, name is 1-Benzyl-4-iodo-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 50877-42-4, Safety of 1-Benzyl-4-iodo-1H-pyrazole

General procedure: To a solution of 4-iodo-1-methyl-1H-pyrazole (3.0 g, 14.4 mmol, 1.0 eq.), 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (xantphos) (835 mg, 1.4 mmol, 0.1 eq.) and palladium(II) acetate (415 mg, 0.7 mmol, 0.05 eq.) in dioxane (72.1 ml, 0.2 M) was added N,N’-diisopropylethylamine (5.0 mL, 28.9 mmol, 2.0 eq.) and benzylmercaptan (2.0 ml, 17.3 mmol, 1.2 eq.). The reaction mixture was stirred at 100 C for 18 h. The reaction mixture was diluted with ethyl acetate (300 mL) and water (150 mL). The aqueous layer was extracted with ethyl acetate (150 mL). The combined organic layers were dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by column chromatography.

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, 1-Benzyl-4-iodo-1H-pyrazole, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Vernier, William F.; Gomez, Laurent; Tetrahedron Letters; vol. 58; 49; (2017); p. 4587 – 4590;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 330792-70-6, These common heterocyclic compound, 330792-70-6, name is 3-Amino-5-(4-phenoxyphenyl)pyrazole-4-carbonitrile, 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.

5-amino-3-(4-phenoxyphenyl)-1H-pyrazole-4-carbonitrile (1.5 g, 5.4 mmol)And a mixture of K2CO3 (2.24 g, 16.3 mmol) in DMF (50 mL),Stir for 45 minutes under nitrogen at 80C.Then, tert-butyl 3-bromo-4-oxopiperidine-1-carboxylate (4.5 g, 16.3 mmol) was added in one portion.The reaction mixture was stirred at 80 C for 1 h.It was then cooled to room temperature and water (150 mL) and EA (150 mL) were added.The aqueous phase was further extracted with EA (100 mL x 3) and the combined organic phases were washed with saturated brine, dried over Na2SO4, concentrated, and purified on a tannin extract column (15 g of silica gel, DCM/MeOH = 400/1 to 200/1).An off-white solid product 3-cyano-2-(4-phenoxyphenyl)-5,6-dihydro-4H-pyrazolo[5′,1′:2,3]imidazo[4, 5-c]tert-Butyl pyridine-7(8H)-carboxylate (850 mg, 35%).

Statistics shows that 3-Amino-5-(4-phenoxyphenyl)pyrazole-4-carbonitrile is playing an increasingly important role. we look forward to future research findings about 330792-70-6.

Reference:
Patent; BEIGENE, LTD; WANG, ZHIWEI; GUO, YUNHANG; (300 pag.)TWI602818; (2017); B;,
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. 155377-19-8, name is Ethyl 3-(trifluoromethyl)pyrazole-4-carboxylate, A new synthetic method of this compound is introduced below., HPLC of Formula: C7H7F3N2O2

Ethyl 3-(trifluoromethyl)-1H-pyrazole-4-carboxylate (95.00 g, 0.456 mol) was dissolved in dry THF (1 L) and the resulting solution cooled in an acetone/ice bath. A 1M solution of LiAlH4 in THF (550 mL, 0.550 mol) was added over 30 min, keeping the temperature <10 C. Cooling was then removed and the reaction mixture was stirred at RT for 4 h. The reaction was again cooled and a 1:1 THF:water solution (250 mL) was added with cooling (maintaining the temperature <20 C.), followed by 5M HCl (160 mL) to neutrality/pH 6. EtOAc (1.5 L) was added and the mixture stirred for 30 min then left to settle overnight. The resulting grey granular solid was removed by filtration through dicalite and washed with EtOAc. The combined filtrates were washed with brine and dried over MgSO4, before concentrating in vacuo to give a white solid (76.00 g, 0.457 mol, 100%).1H NMR (400 MHz, CD3OD): delta 4.61 (s, 2H), 7.75 (s, 1H). 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; N.V. Organon; US2009/131455; (2009); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics