Category: 578008-32-9

These common heterocyclic compound, 578008-32-9, name is tert-Butyl 3-amino-5-methyl-1H-pyrazole-1-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. Product Details of 578008-32-9

Intermediate 90(S)-4-(3-((tert-Butyldimethylsilyloxy)methyl)morpholino)-6-(l-(3,5-difluoropyridin-2-vD-2- methoxyethoxy)-5-fluoro-N-(5-methyl-lH-pyrazol-3-yl)pyrimidin-2-amine (3,S<)-3-({[fert-Butyl(dimethyl)silyl]oxy}methyl)-4-{2-chloro-6-[l-(3,5-difluoropyridin-2-yl)-2- methoxyethoxy]-5-fluoropyrimidin-4-yl}morpholine (Intermediate 62), tert-butyl 3-amino-5- methyl-lH-pyrazole-1-carboxylate (Intermediate 10), BINAP, Pd2(dba)3, and CS2CO3 in dioxane (2 ml) was heated at 950C for 8h. LCMS indicated complete reaction. Methanol (1 ml) was added and the reaction was stirred at r.t for Ih. Solvent was removed under reduced pressure and the reaction mixture was purified by ISCO column. The material obtained was directly used in the subsequent step without further purification. LCMS: 610[M+eta]+. The synthetic route of tert-Butyl 3-amino-5-methyl-1H-pyrazole-1-carboxylate has been constantly updated, and we look forward to future research findings. Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2008/132502; (2008); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 578008-32-9, These common heterocyclic compound, 578008-32-9, name is tert-Butyl 3-amino-5-methyl-1H-pyrazole-1-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.

The product of the previous step (6.6 g, 14.8 mmol), tert-butyl 3-amino-S-methyl- 1H-pyrazole-1-carboxylate (3.5 g, 17.7 mmol), cesium carbonate (9.61 g, 29.6 mmol) andPd Xphos (2.32 g, 2.95 mmol) were dissolved in dioxane (130 mL) and purged with nitrogen. The reaction mixture was stirred at 110 C for 12 h. The product was combined with the product of a similar reaction, extracted with EtOAc (600 mL) and washed with brine (3 x 300 mL). The organic layer was evaporated. The residue was crystallized to provide the title intermediate (5 g, 58 % yield) and 2 g of cmde product which waspurified by preparative HPLC (method 2).

Statistics shows that tert-Butyl 3-amino-5-methyl-1H-pyrazole-1-carboxylate is playing an increasingly important role. we look forward to future research findings about 578008-32-9.

Reference:
Patent; THERAVANCE BIOPHARMA R&D IP, LLC; HUDSON, Ryan; KOZAK, Jennifer; FATHEREE, Paul R.; PODESTO, Dante D.; BRANDT, Gary E.L.; FLEURY, Melissa; BEAUSOLEIL, Anne-Marie; HUANG, Xiaojun; THALLADI, Venkat R.; (121 pag.)WO2016/191524; (2016); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electric Literature of 578008-32-9, A common heterocyclic compound, 578008-32-9, name is tert-Butyl 3-amino-5-methyl-1H-pyrazole-1-carboxylate, molecular formula is C9H15N3O2, 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.

Example 10; 3-{[4-(Azetidin-l-ylcarbonyl)phenvnoxy}-iV-(5-methyl-lH-pyrazol-3-yl)- 5- [(3S)-tetr ahydrofur an-3-yloxyl benzamide; l-Chloro-N,N,2-trimethyl-l-propenylamine (0.145 mL, 1.10 mmol) was added to a solution of 3-{ [4-(azetidin- 1 -ylcarbonyl)phenyl]oxy } -5-[(3S)-tetrahydrofuran-3- yloxy]benzoic acid (350 mg, 0.92 mmol) in DCM (6 mL) and stirred at RT for 30 – 40min. 1,1-Dimethylethyl 3-amino-5-methyl-lH-pyrazole-l-carboxylate (361 mg, 1.83 mmol) and pyridine (0.148 mL, 1.83 mmol) were added and the reaction stirred at RT for 2 hours. The solvent was removed in vacuo, water (20 mL) added and the mixture extracted with ethyl acetate (3 x 20 mL). The extracts were combined and washed with 2Nu hydrochloric acid (20 mL), a saturated solution of sodium bicarbonate (20 mL), water (20 mL), brine (20 mL), dried (MgSO4) and evaporated in vacuo. The crude product was chromatographed on silica, eluting with a gradient of 0- 10% methanol in DCM, to give a white solid which was taken up in acetonitrile (2 mL) and heated in a microwave reactor at 160C for 10 minutes. EPO The reaction mixture was evaporated and the residue chromatographed on silica, eluting with 0-5% methanol in DCM, to give the desired compound as a white foam (50 mg). 1H NMR delta (CDCl3): 2.11 – 2.29 (m, 2H), 2.32 (s, 3H), 2.32 – 2.40 (m, 2H), 3.88 – 4.02 (m, 4H), 4.23 (t, 2H), 4.35 (t, 2H), 4.95 – 4.99 (m, IH), 6.56 (s, IH), 6.71 (t, IH), 7.02 (d, 2H), 7.13 (s, IH), 7.21 (s, IH), 7.64 (d, 2H), 9.06 (s, IH); m/z 463 (M+H)+, 461 (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; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2007/17649; (2007); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Application of 578008-32-9, A common heterocyclic compound, 578008-32-9, name is tert-Butyl 3-amino-5-methyl-1H-pyrazole-1-carboxylate, molecular formula is C9H15N3O2, 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.

Step D: To 4-chloro-2-[difluoro-(5-fluoro-pyridin-2-yl)-methyl]-8-bromo-quinazoline (0.19 g, 0.49 mmol) in DMA (1.0 mL) were added 3-amino-5-methyl-pyrazole-1-carboxylic acid tert-butyl ester (0.30 g, 1.53 mmol) and HOAc (0.065 mL, 1.1 mmol) and the mixture was heated to 100 C. for 5 h. The mixture was allowed to cool to rt and purified by reverse phase HPLC (ammonium acetate modifier). Fraction 1 containing pure product was treated with saturated aq NaHCO3 (2-4 mL) and concentrated under reduced pressure. The aqueous residue was extracted with DCM (3×30 mL) and the combined extracts were washed with sat aqueous NaHCO3 (10 mL) and brine (10 mL), dried over MgSO4, filtered, and concentrated to dryness under reduced pressure to afford 8-bromo-2-(difluoro(5-fluoropyridin-2-yl)methyl)-N-(5-methyl-1H-pyrazol-3-yl)quinazolin-4-amine (48 mg, 20%) as a white solid. 1H NMR (300 MHz, DMSO-d6) delta 12.22 (br s, 1H), 10.87 (br s, 1H), 8.57-8.81 (m, 2H), 8.24 (d, J=7.5 Hz, 1H), 8.02 (d, J=5.3 Hz, 2H), 7.54 (t, J=7.9 Hz, 1H), 5.95 (s, 1H), 2.17 (s, 3H); LC-MS (ESI) m/z 449/451 (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; Hadd, Michael J.; Holladay, Mark W.; Rowbottom, Martin; US2012/53174; (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. 578008-32-9, name is tert-Butyl 3-amino-5-methyl-1H-pyrazole-1-carboxylate, A new synthetic method of this compound is introduced below., name: tert-Butyl 3-amino-5-methyl-1H-pyrazole-1-carboxylate

Step D: To 4-chloro-2-[difluoro-(5-fluoro-pyridin-2-yl)-methyl]-8-methylquinazoline (0.255 g, 0.79 mmol) in DMA (2 mL) were added 3-amino-5-methyl-pyrazole-1-carboxylic acid tert-butyl ester prepared according to US2007/219195 (0.31 g, 1.58 mmol) and acetic acid (0.15 mL) and the mixture was heated at 100 C. for 6.5 h. The mixture was allowed to cool to rt and then was purified by reverse phase HPLC using an ammonium acetate modifier. Fraction 1 containing pure product were combined, treated with saturated aq NaHCO3 and concentrated under reduced pressure. The aqueous residue was extracted with DCM and the combined extracts were washed with saturated aq NaHCO3 and brine, dried over MgSO4, filtered, and concentrated under reduced pressure to afford 2-(difluoro(5-fluoropyridin-2-yl)methyl)-8-methyl-N-(5-methyl-1H-pyrazol-3-yl)quinazolin-4-amine (28 mg, 13%). 1H NMR (300 MHz, DMSO-d6) delta 12.15 (br s, 1H), 10.57 (s, 1H), 8.67 (s, 1H), 8.50 (d, J=8.3 Hz, 1H), 7.92-8.11 (m, 2H), 7.75 (d, J=7.0 Hz, 1H), 7.52 (t, J=7.6 Hz, 1H), 5.96 (s, 1H), 2.59 (s, 3H), 2.17 (s, 3H); LC-MS (ESI) m/z 385 (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; Hadd, Michael J.; Holladay, Mark W.; Rowbottom, Martin; US2012/53174; (2012); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 578008-32-9,Some common heterocyclic compound, 578008-32-9, name is tert-Butyl 3-amino-5-methyl-1H-pyrazole-1-carboxylate, molecular formula is C9H15N3O2, 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 C: To 4-chloro-2-(difluoro(5-fluoropyridin-2-yl)methyl)-7-methoxyquinazoline (355 mg, 0.91 mmol) in DMF (5.0 mL) at rt were added tert-butyl 3-amino-5-methyl-1H-pyrazole-1-carboxylate (0.448 g, 2.27 mmol) and DIEA (0.40 mL, 2.3 mmol), and the mixture was stirred at rt for 3 h. The mixture was purified by preparative reverse-phase HPLC using TFA as a modifier, and the fractions containing the desired product were neutralized with saturated aq NaHCO3 and extracted with EtOAc (100 mL). The organic layer was separated, washed with brine (2×10 mL), dried over MgSO4, filtered, and concentrated under reduced pressure to afford tert-butyl 3-(2-(difluoro(5-fluoropyridin-2-yl)methyl)-7-methoxyquinazolin-4-ylamino)-5-methyl-1H-pyrazole-1-carboxylate as a clear oil (104 mg).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route tert-Butyl 3-amino-5-methyl-1H-pyrazole-1-carboxylate, its application will become more common.

Reference:
Patent; Hadd, Michael J.; Holladay, Mark W.; Rowbottom, Martin; US2012/53174; (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. 578008-32-9, name is tert-Butyl 3-amino-5-methyl-1H-pyrazole-1-carboxylate, A new synthetic method of this compound is introduced below., Product Details of 578008-32-9

Nitrogen was bubbled through a mixture of (S) -2,6- dichloro-4- (3-fluororhoyrrolidin-1-yl) pyridine (600 mg, 2.6 mmol) , tert-butyl S-amino-S-methyl-lH-pyrazole-l-carboxylate(510 mg, 2.6 mmol), Pd2dba3 (119 mg) , xantphos (150 mg) , and sodium carbonate (382 mg, 3.6 mmol) in dioxane (10 mL) . The mixture was heated to 140 0C for 45 minutes and then to 170 0C for 15 minutes in the microwave. After filtration through Celite and a dioxane rinse, the solvents were removed under reduced pressure. The residue was purified by column chromatography (SiO2 (75 mL) , CH2C12/2.5-7% 2-propanol; TLC: CH2C12/5% 2-propanol, Rf=O.3) to yield 230 mg of the desired product as an off-white solid (HPLC: Rf=7.341 minutes) .

The synthetic route of 578008-32-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; WO2008/147626; (2008); A2;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Synthetic Route of 578008-32-9, 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 578008-32-9 as follows.

Typical procedure for the Buchwald reaction with terf-butoxycarbonyl protected pyrazole:2-(2-Chloro-4-trifluoromethyl-phenyl)-4-(5-methyl-lH-pyrazol-3-ylamino)-2H- phthalazin- 1 -one4-Bromo-2-(2-cUoro-4-trifluoromethyl-phenyl)-2H-phthalazin-l-one (obtained from the above phthalazine-l,4-dione by bromination with POBr3 in analogy to Method R, as reported above) (0.15g, 0.37mmol), 3-amino-5-methyl-pyrazole-l- carboxylic acid tert-butyl ester (0.08Og, 0.41mmol), Cs2CO3 (0.033g, 0.34mmol), tris-(dibenzylideneacetone)-dipalladium (0.017g, 0.019mmol) and 4,5- bis(diphenylphosphino)-9,9-dimethylxanthene (0.022g, 0.037mmol) in 2 ml dry dioxane under nitrogen were heated to 100C for 18 hours, and then allowed to cool to room temperature. H2O was added and the solvent was evaporated in vacuum. The resulting solid was collected by filtration. Purification of the raw product by preparative HPLC gave the title compound (0.069g, 44% yield). 1H- EPO NMR: (400 MHz, D6-DMSO) 11.92 (IH, s), 9.34 (IH, s), 8.54 (IH, d), 8.35 (IH, d), 8.14 (IH, s), 8.01 (IH, t), 7.92 (3H, m), 6.06 (IH, s), 2.14 (3H, s); MS (ESI+) = 420.23 (M+H)+.

According to the analysis of related databases, 578008-32-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; WO2006/32518; (2006); 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. 578008-32-9, name is tert-Butyl 3-amino-5-methyl-1H-pyrazole-1-carboxylate, This compound has unique chemical properties. The synthetic route is as follows., Formula: C9H15N3O2

To a solution of 2-(3-bromophenyl)acetic acid (0.5g, 2.32mmol) in DCM (20mL) was added EDCI (0.88g, 0.4.65mmol) at 0 C followed by DIPEA (1.l2mL, 6.97mmol) and finally added tert-butyl 3-amino-5-methyl- 1 H-pyrazole- 1 -carboxylate (0.4g, 2.O9mmol). The reaction mass was stined for 12h at room temperature. The reaction mixture was quenched with ice-water and diluted with DCM. The aqueous layer was separated and extracted with ethyl acetate (2x25mL). The combined organic phase was washed with brine, dried over Na2504, filtered and concentrated under reduced pressure and purified by eluting with 20% ethyl acetate-hexane in combiflash to afford the title compound (0.3g, 60%). LCMS: mlz = 395.9 (M+H).

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 578008-32-9.

Reference:
Patent; AURIGENE DISCOVERY TECHNOLOGIES LIMITED; SAMAJDAR, Susanta; PODDUTOORI, Ramulu; PANDIT, Chetan; MUKHERJEE, Subhendu; GOSWAMI, Rajeev; (126 pag.)WO2016/193939; (2016); 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. 578008-32-9, name is tert-Butyl 3-amino-5-methyl-1H-pyrazole-1-carboxylate, A new synthetic method of this compound is introduced below., Recommanded Product: tert-Butyl 3-amino-5-methyl-1H-pyrazole-1-carboxylate

2-(2-Chloro-4-trifluoromethyl-phenyl)-4-(5-methyl-1H-pyrazol-3-ylamino)-2H-phthalazin-1-one: 4-Bromo-2-(2-chloro-4-trifluoromethyl-phenyl)-2H-phthalazin-1-one (obtained from the above phthalazine-1,4-dione by bromination with POBr3 in analogy to Method R, as reported above) (0.15 g, 0.37 mmol), 3-amino-5-methyl-pyrazole-1-carboxylic acid tert-butyl ester (0.080 g, 0.41 mmol), Cs2CO3 (0.033 g, 0.34 mmol), tris-(dibenzylideneacetone)-dipalladium (0.017 g, 0.01 9 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.022 g, 0.037 mmol) in 2 ml dry dioxane under nitrogen were heated to 100 C. for 18 hours, and then allowed to cool to RT. H2O was added and the solvent was evaporated in vacuum. The resulting solid was collected by filtration. Purification of the raw product by preparative HPLC gave the title compound (0.069 g, 44% yield). 1H-NMR: (400 MHz, D6-DMSO) 11.92 (1H, s), 9.34 (1H, s), 8.54 (1H, d), 8.35 (1H, d), 8.14 (1H, s), 8.01 (1H, t), 7.92 (3H, m), 6.06 (1H, s), 2.14 (3H, s); MS (ESI+)=420.23 (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; Roche Palo Alto LLC; US2007/219195; (2007); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics