Tag: M.W:200-300

Synthetic Route of 50877-41-3, 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. 50877-41-3 name is 1-Benzyl-4-bromo-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.

Preparation of Compound 4003, 3-{5-(1-ben2yl-1M-pyrazol-4-yl}-1W-indol-1-yl}-iV}W- dimethylpropan-1 -amine 1-Ben2y-4-bromo-1 H-pyrazole (237 mg, 1.0 mmol), 1-{3-(dimethylamino)propyl)-1H~ indoi-5-ylboronic acid (180 mg, 0,73 mmol) and Na2C03 (315 mg, 3.0 mmol) were dissolved in a mixture of DMF (8 mL), EtOH (2 mL) and water (2 mL). Pd(PPh3)4 (115 mg, 0,1 mmol) was added under a nitrogen atmosphere and the mixture was heated at 100 C for 2 hours. Water (40 mL) was added and the resulting precipitate was collected, redissolved in EtOAc, dried over Na2S0 , and concentrated. The residue was purified by column chromatography (silica gel, D-GM:MeQH=15:1 ), followed b prep- TLC to afford the product (11 mg, 4%). 1H NMR (400 MHz, CDCI3): delta 7.84 (s, 1H), 7.71 (s, 1 H), 7.62 (s, 1 H), 7,36-7.26 (m, 7H), 7,10 (d, J ~ 3.2 Hz, 1 H), 6.46 (d, J ~ 2.8 Hz, 1H), 5.35 (s, 2HJ, 4.19 (t, J – 7.0 Hz, 2H), 2.23-2.20 (m, 8H), 2.00-1.98 (m, 2H).

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

Reference:
Patent; NOVOGEN LTD; JAMES, Ian; DIXON, Ian; FEUTRILL, John; CUZZUPE, Anthony; TREUTLEIN, Herbert; ZENG, Jun; NERO, Tracy; WO2015/74123; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 35715-72-1, 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. 35715-72-1 name is 4-(Chloromethyl)-1-(2-fluorophenyl)-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.

To a mixture of 237 4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidine (Preparation 71, 20 g, 71.7 mmol) in 21 DMF (200 mL) was added 116 K2CO3 (49.5 g, 358.5 mmol) and the mixture stirred for 10 min at rt before 239 4-(chloromethyl)-1-(2-fluorophenyl)-1H-pyrazole (Preparation 98, 20 g, 95.2 mmol) was added. The resulting mixture was stirred at 60 C. for 6 hr, filtered and concentrated under reduced pressure to give a crude product which was washed with EtOAc and water to afford the 197 title compound (20 g, 62.5%) as a yellow solid. 1HNMR (400 MHz, CDCl3): 5.41 (s, 2H), 7.20-7.32 (m, 3H), 7.42 (s, 1H), 7.72 (s, 1H), 7.84-7.87 (m, 1H), 8.05 (d, 1H), 8.68 (s, 1H). LCMS m/z=453.9 [MH]+

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 4-(Chloromethyl)-1-(2-fluorophenyl)-1H-pyrazole, and friends who are interested can also refer to it.

Reference:
Patent; CYSTIC FIBROSIS FOUNDATION THERAPEUTICS, INC.; Strohbach, Joseph Walter; Limburg, David Christopher; Mathias, John Paul; Thorarensen, Atli; Denny, Rajiah Aldrin; Zapf, Christoph Wolfgang; Elbaum, Daniel; Gavrin, Lori Krim; Efremov, Ivan Viktorovich; (159 pag.)US2018/141954; (2018); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 575452-22-1, 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. 575452-22-1, name is 1-(1-Ethoxyethyl)-4-iodo-1H-pyrazole belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.

To a solution of 1-(1-etboxyethyl)-4-iodo-IH-pyrazole (84a)(5 g, 18.79 mmol)(Prepared as reported by Lin, Qiyan et al; Organic Leilers I 1(9): 1999-2002 (2009)) in ether (16 mL) cooled to -78C was added dropwise a solution of n-butyllithium (12.0 mL, 19.2rnmol) in hexane followed by stirring for 30 mins at -78 C. To the anion formed was addeda solution of 3-nitrobenzaldehyde (31a) (2.87 g, 18.79 mmol) in THF (24 mL) slowly at -78 C, stirred at -78 C for 2 h and then at room temperature for 2 h. The reaction mixturewas quenched with saturated amnionium chloride (50 m.L). The organic layer was separatedand the aqueous phase was extracted with ethyl acetate (75 mL). The organic layers werecombined washed with brine (60 rnL), dried over MgSO4, filtered and concentrated invacuum. The residue obtained was purified by flash column chromatography [(silica gel 80 g, eluting with hexanes/ethyl acetate (1:0 to 1: 1)] to furnish (I -(I -ethoxyethyl)- I H-pyrazol4-yl)(3-nitrophenyl)methanol (84b) (3.537 g, 64.6%) as a yellow gum; ?H NMR (300 MHz, DMSO-d4) 8.24 (s, I H), 8.11 (ddd, .1 = 8.1, 2.4, 1.1 Hz, I H), 7.82 (ddq, .1 = 7.8, 1.8, 1.0Hz, 1.H), 7.74 (d, .1 0.8 Hz, I H), 7.63 (t, J 7.9 Hz, 1H), 7.37 (s, 1 H), 6.04 (dd, .1 4.8,1.6 Hz, IH), 5.85 (d,.J=4.7 Hz, lH), 5.47 (q,J= 6.0 Hz, IH), 3.43 -3.35 (m, lH). 3.23-3.05 (rn, IH), 1.54 (d, J 6.0 Hz, 3H), 1.00 (td, J = 7.0, 0.6 Hz, 3H); MS (ES+) 314.184M+Na).

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

Reference:
Patent; BIOCRYST PHARMACEUTICALS, INC.; KOTIAN, Pravin, L.; BABU, Yarlagadda, S.; WU, Minwan; CHINTAREDDY, Venkat, R.; KUMAR, V., Satish; ZHANG, Weihe; WO2015/134998; (2015); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 1245772-13-7,Some common heterocyclic compound, 1245772-13-7, name is Methyl 1-(2,2,2-trifluoroethyl)-1H-pyrazole-3-carboxylate, molecular formula is C7H7F3N2O2, 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 256: 2-N-Methyl-2-N-phenyl-6-{5-[1-(2,2,2-trifluoroethyl)-1 H-pyrazol-3-yl]-1 ,2,4- oxadiazol-3-yl}-1 ,3,5-triazine-2,4-diamine (Method 12)Methyl 1-(2,2,2-trifluoroethyl)-1 H-pyrazole-3-carboxylate (Intermediate 204, 0.312 g, 1.5 mmol) was dissolved in a mixture of THF (2 mL), MeOH (2 mL) and water (1 mL); lithium hydroxide (0.188 g, 4.5 mmol) was added and the mixture was stirred at roomtemperature for 16 h. The mixture was concentrated, the residue dissolved in water (1 mL) and the mixture was neutralised. This was extracted with EtOAc (2 x 10 mL), the organic extracts were dried over sodium sulfate and concentrated under vacuum. The crude material was washed with pentane (2 x 10 mL) to afford 1-(2,2,2-trifluoroethyl)-1 H- pyrazole-3-carboxylic acid (0.200 g, 69%). 2-N-methyl-2-N-phenyl-6-{5-[1-(2,2,2- trifluoroethyl)-1 H-pyrazol-3-yl]-1 ,2,4-oxadiazol-3-yl}-1 ,3,5-triazine-2,4-diamine was then prepared from 1-(2,2,2-trifluoroethyl)-1 H-pyrazole-3-carboxylic acid (0.159 g, 0.820 mmol) and 4-amino-N-hydroxy-6-[methyl(phenyl)amino]-1 ,3,5-triazine-2- carboximidamide (prepared in an analogous manner to Intermediate 1 , 0.125 g, 0.483 mmol) according to the method described for Example 251 to afford the title compound (0.110 g, 55%).

The synthetic route of 1245772-13-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NOVARTIS AG; BARKER, Oliver; BENTLEY, Jonathan; BOCK, Mark G.; CAIN, Thomas; CHOVATIA, Praful; DOD, Jennifer Ruth; EUSTACHE, Florence; GLEAVE, Laura; HARGRAVE, Jonathan; HEIFETZ, Alexander; LAW, Richard; RAOOF, Ali; WILLOWS, David; WO2012/35023; (2012); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 75092-25-0, name is Methyl 4-iodo-1-methyl-1H-pyrazole-3-carboxylate, 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 75092-25-0, Product Details of 75092-25-0

5.1.51 Methyl 1-methyl-4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-1H-pyrazole-3-carboxylate (36) To a mixture of 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one (34, 2.3 g, 9.78 mmol) and methyl 4-iodo-1-methyl-1H-pyrazole-3-carboxylate (35, 1.25 g, 4.70 mmol) in DMF (40 mL) and water (10 mL) were added Pd(PPh3)4 (814 mg, 0.71 mmol) and Cs2CO3 (3.06 g, 9.40 mmol), and the mixture was stirred at 80 C for 12 h. The mixture was concentrated in vacuo, and the residue was purified by silica gel column chromatography (0-5% MeOH in CHCl3) to give 36 (812 mg, 70%) as colorless solid. 1H NMR (DMSO-d6) delta 3.44 (s, 3H), 3.74 (s, 3H), 3.91 (s, 3H), 6.39 (d, 1H, J = 9.3 Hz), 7.51 (dd, 1H, J = 9.4, 2.6 Hz), 7.86 (d, 1H, J = 2.6 Hz), 7.94 (s, 1H); MS (ESI) m/z 248 [M+H]+.

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

Reference:
Article; Hamaguchi, Wataru; Masuda, Naoyuki; Miyamoto, Satoshi; Shiina, Yasuhiro; Kikuchi, Shigetoshi; Mihara, Takuma; Moriguchi, Hiroyuki; Fushiki, Hiroshi; Murakami, Yoshihiro; Amano, Yasushi; Honbou, Kazuya; Hattori, Kouji; Bioorganic and Medicinal Chemistry; vol. 23; 2; (2015); p. 297 – 313;,
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. 51516-68-8, name is 5-Amino-1-(3-chlorophenyl)-1H-pyrazole-4-carbonitrile, This compound has unique chemical properties. The synthetic route is as follows., Formula: C10H7ClN4

Title compound 2A, 5-amino-1-(3-chloro-phenyl)-1H pyrazole-4-carbonitrile (0.2 g, 0.91 mmol) was suspended in formamide (10 ml). The suspension was heated to 210C for 1 hour then allowed to cool to room temperature. To the reaction mixture was added water (10 ml), the resultant precipitate was collected by filtration, washed with water (2 x 10 ml) and dried on the filter. The crude solid was then purified by column chromatography with ethyl acetate/heptane (1: 1) as the eluent to give the title compound as a white solid (68 mg, 0.278 mmol, 30%). LC-MS: [M+H]+=246, Rt = 1.06 min, 98% purity.

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 51516-68-8.

Reference:
Patent; DeveloGen Aktiengesellschaft; Evotec AG; EP1746099; (2007); 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. 754219-01-7, name is Ethyl 5-iodo-1-methyl-1H-pyrazole-4-carboxylate, This compound has unique chemical properties. The synthetic route is as follows., Computed Properties of C7H9IN2O2

On the other hand, 5-iodo-1-methylpyrazole-4-carboxylic acid (150 mg, 0.58 mmol), given by hydrolysis of 5-iodo-1-methylpyrazole-4-carboxylic acid ethyl ester (Reference compound No.15-2), and oxalyl chloride (0.053 mL, 0.61 mmol) were stirred at 50C for 1 hour. N,N-Diisopropylethylamine (0.51 mL, 2.9 mmol) and amine-derivative polystyrene(I) were added to a solution of 5-iodo-1-methylpyrazole-4-carbonyl chloride prepared by an above method in anhydrous methylene chloride (3.3 mL), and then the whole was shaken at room temperature for 19 hours. The reaction mixture was filtered, the polystyrene resin was washed with methanol (6.0 mL) and chloroform (6.0 mL) four times alternately, and then the resin was washed with diethyl ether (6.0 mL), and dried under reduced pressure to give amide-derivative polystyrene (II). This resin(II), tris(dibenzylideneacetone)dipalladium(0) (160 mg, 0.17 mmol), 1,1-bis(diphenylphosphino)ferrocene (400 mg, 0.73 mmol), and N,N-diisopropylethylamine (0.60 mL, 3.3 mmol) were suspended in N,N-dimethylacetamide (5.0 mL). This suspension was frozen, allowed to stand under reduced pressure, and melted. This procedure was repeated twice and dissolved oxygen in the solvent was removed, 4-pyridinemethanethiol hydrochloride (0.40 g, 2.70 mmol) was added thereto, and then the reaction mixture was stirred at 60 C under an argon atmosphere for 24 hours. The reaction mixture was filtered, the resulting resin was washed with N,N-dimethylformamide (6.0 mL) twice, with methanol (6.0 mL) and chloroform (6.0 mL) three times alternately, and with diethyl ether (6.0 mL), then dried under reduced pressure. A solution of 20% trifluoroacetic acid in methylene chloride (5.0 mL) was added to this resin, the whole was shaken at room temperature for 30 minutes, and then polystylene resin was filtered out. The filtrate was diluted with methylene chloride (4.0 mL), and then a saturated aqueous sodium hydrogencarbonate solution was added to adjust to pH 7. The methylene chloride layer was evaporated under reduced pressure, and then the resulting residue was purified by silica gel column chromatography to give 7.0 mg of the title compound as a yellow solid. (Yield 36%)1H-NMR(500MHz,CDCl3)delta 2.33(s,6H),3.59(s,3H),3.97(s,2H),6.80(s,1H),6.94(dd,J = 4.4,1.6 Hz,2H), 7.22(s,2H),8.11(s,1H),8.48(dd,J = 4.4,1.6 Hz,2H),8.81(s,1H)

According to the analysis of related databases, 754219-01-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SANTEN PHARMACEUTICAL CO., LTD.; EP1602647; (2005); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 50877-41-3,Some common heterocyclic compound, 50877-41-3, name is 1-Benzyl-4-bromo-1H-pyrazole, molecular formula is C10H9BrN2, 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.

Step 2: Preparation of l-benzyl-4-(l-ethoxyvinyl)-lH-pyrazole [00168] Nitrogen was purged into a solution of l-benzyl-4-bromo-lH-pyrazole (0.55 g, 2.32 mmol) and tributyl(l-ethoxyvinyl)stannane (0.862 niL, 2.55 mmol) in toluene (15 niL) for 15 minutes. Then tetrakis(triphenylphosphine)palladium(0) (0.134 g, 0.116 mmol) was added and the reaction mixture was heated at 110 C for 12 h. The reaction mixture was filtered through celite and the filtrate was evaporated to afford the title compound l-benzyl-4-(l-ethoxyvinyl)- lH-pyrazole (0.52 g, crude) as a black liquid. The crude material was as such taken for next step without further purification.

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

Reference:
Patent; MNEMOSYNE PHARMACEUTICALS, INC.; ANDERSON, David, R.; VOLKMANN, Robert, A.; MENNITI, Frank, S.; (181 pag.)WO2016/49165; (2016); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

923283-63-0, name is 1-tert-Butyl 3-methyl 4-amino-1H-pyrazole-1,3-dicarboxylate, 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. HPLC of Formula: C10H15N3O4

Compound 27: Formamidine acetate (40.3 mmol, 4.2 g) was added to a solution containing 26 (8.85 g, 36.7 mmol) in Hunig’s base (40 mL) and n-BuOH (40 mL). The stirred solution was heated at 110 C. for 1 hour. After cooling to ambient temperature the resulting solid was collected, washed with dichloromethane, and dried under reduced pressure to afford 27 (4.46 g, 89%), ES (+) MS m/e=137.

The synthetic route of 923283-63-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Sunesis Pharmaceuticals, Inc.; US2007/27166; (2007); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Some common heterocyclic compound, 73387-52-7, name is 5-(4-Bromophenyl)-1-methyl-1H-pyrazole, molecular formula is C10H9BrN2, 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: 5-(4-Bromophenyl)-1-methyl-1H-pyrazole

Inside an argon filled glove bag, 3.41 g of sodium f-butoxide was placed in an oven-dried flask. 7.03 g of 5-(4-bromophenyl)-1 -methyl-1 /-/-pyrazole, 0.328 g of palladium acetate, and 0.7720 g of 1 ,1 ‘-bis(di-i-propylphosphino)-ferrocene were added, and the mixture was evacuated/nitrogen filled three times. 50 ml_ of anhydrous 1 ,4-dioxane was added, followed by the addition of 7.00 ml_ of triisopropylsilanethiol. After heating at reflux for 40 minutes, the reaction mixture was cooled, and 20 ml_ of 2.5 N aqueous sodium hydroxide and 15 ml_ of DMSO were then added under nitrogen. The reaction was stirred vigorously at room temperature for 40 minutes and then diluted into ether. The addition of 125 ml_ of 5% aqueous sodium chloride containing ~5 ml_ of concentrated hydrochloric acid adjusted the pH of the aqueous phase to 4, and the mixture was extracted, separated, extracted the aqueous again with ether, combined the ether extracts, dried with magnesium sulfate, filtered, and concentrated to give a dark liquid. The crude product was diluted into ether, extracted twice with 100-mL portions of 0.5 N aqueous sodium hydroxide (discarded the ether), combined the aqueous extracts, extracted the aqueous solution with ether (discarded ether), carefully adjusted the pH to 3 with concentrated hydrochloric acid, extracted three times with ether, combined the ether extracts, dried with magnesium sulfate, filtered, concentrated, and flash chromatographed on silica gel to give 4.4600 gm of product. 1 H NMR (400 MHz, DMSO-c/e) delta ppm 3.83 (s, 3 H) 5.65 (s, 1 H) 6.36 (d, J=1.95 Hz, 1 H) 7.40 (s, 4 H) 7.44 (d, J=1.95 Hz, 1 H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 73387-52-7, its application will become more common.

Reference:
Patent; PFIZER INC.; WO2009/69044; (2009); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics