Category: 78531-29-0

Wellaway, Christopher R.; Amans, Dominique; Bamborough, Paul; Barnett, Heather; Bit, Rino A.; Brown, Jack A.; Carlson, Neil R.; Chung, Chun-wa; Cooper, Anthony W. J.; Craggs, Peter D.; Davis, Robert P.; Dean, Tony W.; Evans, John P.; Gordon, Laurie; Harada, Isobel L.; Hirst, David J.; Humphreys, Philip G.; Jones, Katherine L.; Lewis, Antonia J.; Lindon, Matthew J.; Lugo, Dave; Mahmood, Mahnoor; McCleary, Scott; Medeiros, Patricia; Mitchell, Darren J.; O’Sullivan, Michael; Le Gall, Armelle; Patel, Vipulkumar K.; Patten, Chris; Poole, Darren L.; Shah, Rishi R.; Smith, Jane E.; Stafford, Kayleigh A. J.; Thomas, Pamela J.; Vimal, Mythily; Wall, Ian D.; Watson, Robert J.; Wellaway, Natalie; Yao, Gang; Prinjha, Rab K. published the artcile< Discovery of a Bromodomain and Extraterminal Inhibitor with a Low Predicted Human Dose through Synergistic Use of Encoded Library Technology and Fragment Screening>, SDS of cas: 78531-29-0, the main research area is dimethylpyridone benzimidazole compound preparation BET protein inhibitor.

The bromodomain and extraterminal (BET) family of bromodomain-containing proteins are important regulators of the epigenome through their ability to recognize N-acetyl lysine (KAc) post-translational modifications on histone tails. These interactions have been implicated in various disease states and, consequently, disruption of BET-KAc binding has emerged as an attractive therapeutic strategy with a number of small mol. inhibitors now under investigation in the clinic. However, until the utility of these advanced candidates is fully assessed by these trials, there remains scope for the discovery of inhibitors from new chemotypes with alternative physicochem., pharmacokinetic, and pharmacodynamic profiles. Herein, we describe the discovery of a candidate-quality dimethylpyridone benzimidazole compound which originated from the hybridization of a dimethylphenol benzimidazole series, identified using encoded library technol., with an N-Me pyridone series identified through fragment screening. Optimization via structure- and property-based design led to I-BET469, which possesses favorable oral pharmacokinetic properties, displays activity in vivo, and is projected to have a low human efficacious dose.

Journal of Medicinal Chemistry published new progress about Bromodomain and extra-terminal domain-containing proteins Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 78531-29-0 belongs to class ethers-buliding-blocks, and the molecular formula is C5H13NO2, SDS of cas: 78531-29-0.

Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Rianjongdee, Francesco; Atkinson, Stephen J.; Chung, Chun-wa; Grandi, Paola; Gray, James R. J.; Kaushansky, Laura J.; Medeiros, Patricia; Messenger, Cassie; Phillipou, Alex; Preston, Alex; Prinjha, Rab K.; Rioja, Inmaculada; Satz, Alexander L.; Taylor, Simon; Wall, Ian D.; Watson, Robert J.; Yao, Gang; Demont, Emmanuel H. published the artcile< Discovery of a Highly Selective BET BD2 Inhibitor from a DNA-Encoded Library Technology Screening Hit>, Name: 1,3-Dimethoxypropan-2-amine, the main research area is epigenetics chem probe BET BD2 DNA encoded library bromodomains.

Second-generation bromodomain and extra terminal (BET) inhibitors, which selectively target one of the two bromodomains in the BET proteins, have begun to emerge in the literature. These inhibitors aim to help determine the roles and functions of each domain and assess whether they can demonstrate an improved safety profile in clin. settings compared to pan-BET inhibitors. Herein, we describe the discovery of a novel BET BD2-selective chemotype using a structure-based drug design from a hit identified by DNA-encoded library technologies, showing a structural differentiation from key previously reported greater than 100-fold BD2-selective chemotypes GSK620, GSK046, and ABBV-744. Following a structure-based hypothesis for the selectivity and optimization of the physicochem. properties of the series, we identified 60 (GSK040)(I), an in vitro ready and in vivo capable BET BD2-inhibitor of unprecedented selectivity (5000-fold) against BET BD1, excellent selectivity against other bromodomains, and good physicochem. properties. This novel chem. probe can be added to the toolbox used in the advancement of epigenetics research.

Journal of Medicinal Chemistry published new progress about Bromodomain (BD2). 78531-29-0 belongs to class ethers-buliding-blocks, and the molecular formula is C5H13NO2, Name: 1,3-Dimethoxypropan-2-amine.

Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

78531-29-0, name is 1,3-Dimethoxypropan-2-amine, belongs to ethers-buliding-blocks compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. Quality Control of 1,3-Dimethoxypropan-2-amine

General procedure: Example 6B (0.018 g, 0.05 mmol) was dissolved in acetonitrile (0.5 ml), and treated with potassium carbonate (0.021 g, 0.15 mmol) and 1 -(2-chloroethyl)pyrrolidine (0.017 g, 0.1 mmol). The reaction mixture was heated via microwave at 180 C for 30 minutes, concentrated in vacuo, and submitted to reverse-phase HPLC (as described in Example 6C) to provide the title compound.

The synthetic route of 78531-29-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ABBVIE INC.; SWEIS, Ramzi F.; CURTIN, Michael L.; PLIUSHCHEV, Marina A.; HANSEN, Todd M.; LONGENECKER, Kenton; WO2013/170118; (2013); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Application of 78531-29-0, A common heterocyclic compound, 78531-29-0, name is 1,3-Dimethoxypropan-2-amine, molecular formula is C5H13NO2, 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.

[0407] In Examples, a room temperature usually indicates10 to 30 C. ?H NMR indicates a proton nuclear magnetic resonance spectrum, and chemical shift (6) is expressed in ppm, using tetramethylsilane as an internal standard substance.; [0432] The intermediate compound (1) (0.24 g, 1.0 mmol), 1,3-dimethoxypropane-2-amine (0.15 g, 1.2 mmol), and HOST (0.01 g, 0.1 mmol) were added to chloroform (Amylene-added product) (2.5 mE). Afier EDCD (0.24 g, 1.2 mmol) was added to the mixed liquid at room temperature, the mixture was stirred at room temperature overnight. Thereafier, dilute hydrochloric acid was added to the reaction mixture, followed by extraction with chloroform two times. Afier organic layer was passed through a short column to remove impurities, this was concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 0.26 g of a compound offollowing formula: (hereinafier, referred to as compound (12)).; [0433] ?H-NMR (CDC13, TMS, oe(ppm)): 3.38 (6H, s),3.49-3.53 (2H, m), 3.57-3.61 (2H, m), 4.36-4.43 (1H, m),4.60 (2H, s), 4.65 (2H, s), 6.72 (1H, s), 7.14 (1H, brs),7.30-7.40 (5H, m)

The synthetic route of 78531-29-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SUMITOMO CHEMICAL COMPANY, LIMITED; MITSUDERA, Hiromasa; OKAJIMA, Mayumi; KOWATA, Ayano; AWASAGUCHI, Kenichiro; UJIHARA, Kazuya; (108 pag.)US2017/295789; (2017); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Application of 78531-29-0, A common heterocyclic compound, 78531-29-0, name is 1,3-Dimethoxypropan-2-amine, molecular formula is C5H13NO2, 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.

4-Bromo-1-fluoro-2-nitrobenzene (commcerciaHy available from, for example, Aldrich) (50 g, 227 mmol) and l,3-dimethoxypropan-2-amine (commcerciaHy available from, for example, Aldrich) (32.5 g, 273 mmol) were dissolved in acetonitrile (300 mL) and potassium carbonate (47.1 g, 341 mmol) was added, then the mixture was stirred at 80 C for 6 h, then the mixture was allowed to cool and stood over the weekend at room temperature. The mixture was diluted with water (500 mL) and extracted with EtOAc (2 x 500 mL). The organic layer was washed with water (300 mL) and brine (300 mL), dried and evaporated in vacuo to give the title compound (70 g, 220 mmol, 97% yield) as an orange solid.

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; Glaxosmithkline Intellectual Property Co.,Ltd; BROWN, JOHN ALEXANDER; G HUMPHREYS, PHILIP; JONES, KATHERINE LOUISE; WELLAWAY, CHRISTOPHER ROLAND; (48 pag.)TW2017/4230; (2017); A;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

78531-29-0, name is 1,3-Dimethoxypropan-2-amine, belongs to ethers-buliding-blocks compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. Safety of 1,3-Dimethoxypropan-2-amine

General procedure: Example 6B (0.018 g, 0.05 mmol) was dissolved in acetonitrile (0.5 ml), and treated with potassium carbonate (0.021 g, 0.15 mmol) and 1 -(2-chloroethyl)pyrrolidine (0.017 g, 0.1 mmol). The reaction mixture was heated via microwave at 180 C for 30 minutes, concentrated in vacuo, and submitted to reverse-phase HPLC (as described in Example 6C) to provide the title compound.

The synthetic route of 78531-29-0 has been constantly updated, and we look forward to future research findings.

Synthetic Route of 78531-29-0,Some common heterocyclic compound, 78531-29-0, name is 1,3-Dimethoxypropan-2-amine, molecular formula is C5H13NO2, 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.

Intermediate 222: (4-((1,3-Dimethoxypropan-2-yl)amino)-3-nitrophenyl)methanol To a solution of (4-fluoro-3-nitrophenyl)methanol (16 g, 93 mmol) in THF (80 mL) was added 1,3- dimethoxypropan-2-amine (10 g, 84 mmol) and DIPEA (15 mL, 86 mmol). The mixture was split into seven portions and heated under microwave conditions at 100 C for 7 hours. The reaction mixture was partitioned between ethyl acetate (3 x 500 mL) and saturated aqueous sodium bicarbonate solution (750 mL). The organic layers were combined, washed with saturated brine (500 mL), and evaporated under reduced pressure. The sample was loaded in dichloromethane and purified SPE (silica, 100 g) using a gradient of 0-80% EtOAc in cyclohexane. The appropriate fractions were combined and evaporated under reduced pressure to give a the title compound (12.0 g, 44.4 mmol). LCMS (System B): tRET = 0.85 min, MH+ = 271. Less pure fractions were combined and evaporated. The sample was loaded in dichloromethane and purified by SPE (silica, 100 g) using a gradient of 0- 50 % EtOAc in cyclohexane. The appropriate fractions were combined and evaporated under reduced pressure to give the title compound (3.7 g, 13.69 mmol). LCMS (System J): tRET = 0.85 min, MH+ = 271.

The synthetic route of 78531-29-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; BIT, Rino Antonio; BROWN, John Alexander; HUMPHREYS, Philip G.; JONES, Katherine Louise; (240 pag.)WO2016/146738; (2016); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Adding a certain compound to certain chemical reactions, such as: 78531-29-0, name is 1,3-Dimethoxypropan-2-amine, belongs to ethers-buliding-blocks 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 78531-29-0, Recommanded Product: 1,3-Dimethoxypropan-2-amine

To a dry (0876) 200 round-bottomed flask was added di(2-pyridyl) thionocarbonate (5.34 g, 23.00 mmol) in DCM (73.0 ml). 2-Amino-l,3-dimethoxypropane (commericially available from Combi-Blocks Inc., 2.61 g, 21.90 mmol) in DCM (15 mL) was then added dropwise via an addition funnel over 5 min at RT with stirring. The reaction mixture was stirred at RT for 3.5 h. The reaction mixture was then concentrated in vacuo. The product was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 0% to 50% EtOAc in heptane, to provide the title compound Example 124.1 (3.28 g, 20.34 mmol, 93 % yield) as colorless oil. NMR (400MHz, CDC13) delta 3.95 (quin, J=5.49 Hz, 1 H) 3.50 – 3.60 (m, 4 H) 3.41 (s, 6 H). LCMS (pos.) m/z: 162.2 (M+H)+.

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, 1,3-Dimethoxypropan-2-amine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; AMGEN INC.; CHEN, Yinhong; DEBENEDETTO, Mikkel V.; DRANSFIELD, Paul John; HARVEY, James S.; HOUZE, Jonathan; KHAKOO, Aarif Yusuf; LAI, Su-Jen; MA, Zhihua; NISHIMURA, Nobuko; PATTAROPONG, Vatee; SWAMINATH, Gayathri; YEH, Wen-Chen; RAMSDEN, Philip Dean; SHARMA, Ankit; (321 pag.)WO2018/93576; (2018); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

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. 78531-29-0, name is 1,3-Dimethoxypropan-2-amine, A new synthetic method of this compound is introduced below., Product Details of 78531-29-0

A mixture of [4-BROMO-7- (2,] 4-dichlorophenyl) -2,6-dimethylpyrrolo [1, 2- b] pyridazine (0.143 g, 0.387 mmol), 1, 3-dimethoxypropan-2-amine (0.092 g, 0.774 [MMOL),] [2′-(DICYCLOHEXYLPHOSPHINO)-N, N-DIMETHYL-L, L’-BIPHENYL-2-AMINE] (0. [011] g, 0.029 mmol), Cs2CO3 (0.176 g, 0.542 mmol) and Pd2 (dba) 3 (0.018 g, 0.02 mmol) in DME (5.0 mL) is refluxed for 24 h. After cooling to room temperature, to the mixture is added [1,] 3-dimethoxypropan-2-amine (0.092 g, 0.774 mmol), 2′- (dicyclohexylphosphino)-N, N-dimethyl-1,1′-biphenyl-2-amine (0. [011] g, 0.029 mmol) and Pd2 (dba) 3 (0.018 g, 0.02 mmol). The mixture is refluxed for another 24 h. After cooling to room temperature, the mixture is filtered and washed with EtOAc. The filtrate is concentrated in vacuo to dryness, the residue is subjected to preparative TLC (silica gel, [1/5] EtOAc/heptane) to give 0.07 g (44%) of light yellow solid as the title compound: mp [154-155 C (CH2CL2/HEPTANE) ; LH] NMR (400 MHz, CDCl3) [8] 7.57 (d, J = 2.0 Hz, [1H),] 7.41 (d, J = 8.3 Hz, [1H),] 7. [36] (d, J = 8.3, 2.0 Hz, [1H),] 6. [35] (s, [1H),] 5.65 (s, 1H), 4.88 (d, [J =] 8.4 Hz, [LH),] 3.91-3. 82 (m, 1H), 3.69-3. 66 (m, 2H), 3.61-3. 55 (m, 2H), 3.45 (s, 3H), 3.44 (s, 3H), 2.33 (s, 3H), 2.21 (s, 3H); [13C] NMR (100 MHz, CDC13) [8] 150.4, 142.4, 136.4, 134.3, 134.1, 129.6, 129.3, 126.8, 123.3, 120.6, 119.3, 95.1, 88.0, 70.9, 59.3, 51.3, 22.4, 12.3 ; IR (diffuse reflectance) 3336,2924, 1560, 1490,1372, 1330,1192, 1113,1098, 1078,1051, 961,821, 811,778 cm ; MS [(EI)] m/z 407 (M+), 409 (M+) ; HRMS (FAB) calcd for C2oH23Cl2N302+H 408.1245, found 408.1244 ; Anal. Calcd for C20 H23 C12 N3 [02 :] C, 58.83 ; H, 5.68 ; N, 10.29. Found: C, 58.90 ; H, 5.78 ; N, 10.13.

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; PHARMACIA & UPJOHN COMPANY; WO2004/35586; (2004); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem