BOSENTAN PRECURSOR

New Drug Approvals

N,N′-(6,6′-(2,2-Dimethyl-1,3-dioxolane-4,5-diyl)bis- (methylene)bis(oxy)bis(5-(2-methoxy phenoxy)-2,2′-bipyrimidine-6,4-diyl))bis(4-tert-butylbenzenesulfonamide)

Mp: 72−74 °C.

1 H NMR (400 MHz, CDCl3): δ 1.25 (6H, s), 1.29 (18H, s), 3.84−3.90 (4H, m), 4.27−4.31 (2H, m), 6.84−6.87 (3H, t), 6.97−7.00 (2H, dd), 7.09−7.13 (3H, t), 7.43−7.45 (10H, m), 9.0−9.01 (4H, d), 8.43 (2H, br s);

13C NMR (100 MHz, CDCl3): δ 25.88, 30.02, 34.10, 55.01, 61.53, 77.36, 108.43, 111.4, 118.73, 120.4, 124.09, 124.34, 126.67, 127.38, 128.35, 135.30, 138.25, 144.74, 148.62, 150.99, 156.07, 156.71, 160.56;

MS: m/z 1142.2 (M + H);

Elem. Anal: Found: C 59.87, H 5.20, N 12.38; Calcd for C57H60N10O12S2: C 59.99, H 5.30, N 12.27

Abstract Image

A new and efficient synthetic process for the synthesis of an endothelin receptor antagonist, bosentan monohydrate, involves the coupling of ptert-butyl-N-(6-chloro-5-(2-methoxy phenoxy)-2,2′-bipyrimidin-4-yl)benzenesulfonamide (7) with (2,2-dimethyl-1,3-dioxolane-4,5-diyl)dimethanol (14) as a key step. This new process provides desired bosentan monohydrate (1) with better quality and…

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Heck–Matsuda Reaction in Flow

Abstract Image

Product 3 was obtained as a mixture of diastereomers (58:42). The NMR data are consistent with literature precedent.20a

Major diastereomer: 1H NMR (300 MHz, CDCl3) δ (ppm) 7.25-7.28 (m, 2H), 7.14-7.17 (m, 2H), 5.14 (dd, 1H, J = 2.5, 5.8 Hz), 4.29 (t, 1H, J = 8.3 Hz), 3.79 (dd, 1H, J = 6.9, 8.4 Hz), 3.54-3.62 (m, 1H), 3.38 (s, 3H), 2.32 (dd, 1H, J = 7.7, 12.9 Hz), 2.04 (ddd, 1H, J = 5.1, 9.3, 13.1 Hz);

Minor diastereomer: 1H NMR (300 MHz, CDCl3) δ 7.25-7.28 (m, 4H), 5.16 (d, 1H, J = 4.4 Hz), 4.17 (t, 1H, J = 8.1 Hz), 3.72 (dd, 1H, J = 8.5, 9.7 Hz), 3.42 (s, 3H), 3.32-3.36 (m, 1H), 2.59 (ddd, 1H, J = 5.5, 10.3, 13.7 Hz), 1.91 (ddd, 1H, J = 2.4, 7.7, 10.2 Hz);

13C NMR (75 MHz, CDCl3) δ (ppm) 141.4, 140.0, 132.4, 132.3, 129.1, 128.7, 128.7, 128.5, 105.7, 105.4, 73.7, 73.0, 54.9, 54.7, 43.6, 42.1, 41.4, 41.1.

(20) (a) Oliveira, C. C.; Angnes, R. A.; Correia, C. R. D. J. Org. Chem. 2013, 78, 4373. (b) Oliveira, C. C.; Pfaltz, A.; Correia, C. R. D. Angew. Chem. Int. Ed. 2015, 54, 14036.

The optimization of a palladium-catalyzed Heck–Matsuda reaction using an optimization algorithm is presented. We modified and implemented the Nelder–Mead method in order to perform constrained optimizations in a multidimensional space. We illustrated the power of our modified algorithm through the optimization of a multivariable reaction involving the arylation of a deactivated olefin with an arenediazonium salt. The great flexibility of our optimization method allows to fine-tune experimental conditions according to three different objective functions: maximum yield, highest throughput, and lowest production cost. The beneficial properties of flow reactors associated with the power of intelligent algorithms for the fine-tuning of experimental parameters allowed the reaction to proceed in astonishingly simple conditions unable to promote the coupling through traditional batch chemistry.

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BioAssay Express: models mixing assays & compounds — Cheminformatics 2.0

The latest experimental feature of the BioAssay Express project involves taking all of the curated assays (3500 so far) and their corresponding compounds from PubChem (hundreds of thousands of unique structures) and feeding them all into one giant Bayesian model. Rather than the usual approach of modelling compound ⟹ activity separately for each assay, this approach takes advantage […]

via BioAssay Express: models mixing assays & compounds — Cheminformatics 2.0

Simultaneous rapid reaction workup and catalyst recovery

Green Chemistry International

Simultaneous rapid reaction workup and catalyst recovery

Green Chem., 2016, 18,5769-5772

DOI: 10.1039/C6GC02448C, Communication

Zhichao Lu, Zofia Hetman, Gerald B. Hammond, Bo Xu

By combining reaction work-up and catalyst recovery into a simple filtration procedure we have developed a substantially faster technique for organic synthesis.

By combining reaction work-up and catalyst recovery into a simple filtration procedure we have developed a substantially faster technique for organic synthesis. Our protocol eliminates the time-consuming conventional liquid–liquid extraction and is capable of parallelization and automation. Additionally, it requires only minimal amounts of solvent.

Simultaneous rapid reaction workup and catalyst recovery

Zhichao Lu,a   Zofia Hetman,a   Gerald B. Hammond*a and  Bo Xu*b  

 *Corresponding authors

aDepartment of Chemistry, University of Louisville, Louisville, USA

bCollege of Chemistry, Chemical Engineering and Biotechnology, Donghua University, 2999 North Renmin Lu…

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A catalyst-free 1,3-dipolar cycloaddition of C,N-cyclic azomethine imines and 3-nitroindoles: an easy access to five-ring-fused tetrahydroisoquinolines

Green Chemistry International

A catalyst-free 1,3-dipolar cycloaddition of C,N-cyclic azomethine imines and 3-nitroindoles: an easy access to five-ring-fused tetrahydroisoquinolines

Green Chem., 2016, Advance Article

DOI: 10.1039/C6GC02517J, Communication

Xihong Liu, Dongxu Yang, Kezhou Wang, Jinlong Zhang, Rui Wang

A catalyst-free 1,3-dipolar cycloaddition of C,N-cyclic azomethine imines and 3-nitroindoles has been reported under mild conditions.

A catalyst-free 1,3-dipolar cycloaddition of C,N-cyclic azomethine imines and 3-nitroindoles: an easy access to five-ring-fused tetrahydroisoquinolines

Xihong Liu,a   Dongxu Yang,a   Kezhou Wang,a  Jinlong Zhanga and   Rui Wang*ab  

*Corresponding authors

aSchool of Life Sciences, Institute of Biochemistry and Molecular Biology, Lanzhou University, Lanzhou 730000, P. R. China

bState Key Laboratory of Chiroscience, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, P. R. China

Green Chem., 2016, Advance Article

DOI: 

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Solvent- and halide-free synthesis of pyridine-2-yl substituted ureas through facile C-H functionalization of pyridine N-oxides

Green Chemistry International

Solvent- and halide-free synthesis of pyridine-2-yl substituted ureas through facile C-H functionalization of pyridine N-oxides

Green Chem., 2016, Advance Article

DOI: 10.1039/C6GC02556K, Paper

Valentin A. Rassadin, Dmitry P. Zimin, Gulnara Z. Raskil’dina, Alexander Yu. Ivanov, Vadim P. Boyarskiy, Semen S. Zlotskii, Vadim Yu. Kukushkin

A solvent- and halide-free atom-economical synthesis of practically useful pyridine-2-yl substituted ureas utilizes pyridine N-oxides and dialkylcyanamides.

Solvent- and halide-free synthesis of pyridine-2-yl substituted ureas through facile C–H functionalization of pyridine N-oxides

 *Corresponding authors

aInstitute of Chemistry, Saint Petersburg State University, Universitetskaya Nab. 7/9, 199034 Saint Petersburg, Russia

bUfa State…

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BMS-852927

New Drug Approvals

str1

str1

BMS-852927

CAS 256918-39-4

609.51 MW

C29 H28 Cl2 F2 N2 O4 S MF

2-(2-(2-(2,6-dichlorophenyl)propan-2-yl)-1-(3,3′-difluoro-4′-(hydroxymethyl)-5′-(methylsulfonyl)biphenyl-4-yl)-1H-imidazol-4-yl)propan-2-ol

1H-Imidazole-4-methanol, 2-[1-(2,6-dichlorophenyl)-1-methylethyl]-1-[3,3′-difluoro-4′-(hydroxymethyl)-5′-(methylsulfonyl)[1,1′-biphenyl]-4-yl]-α,α-dimethyl-

Treat metabolic syndrome

Brett Busch, Ph.D.Brett Busch, Ph.D.

https://www.linkedin.com/in/brettbbusch

Exelixis

Brett B. Busch, William C. Stevens, Jr., Ellen K. Kick, Haiying Zhang, Venkataiah Bollu,Richard Martin, Raju Mohan
Applicant Exelixis, Inc.
Brett B. Busch, William C. Stevens, JR., Ellen K. Kick, Haiying Zhang, Venkataiah Bollu,Richard Martin, Raju Mohan
Bristol-Myers Squibb Company, Exelixis Patent Company Llc
  • Originator Exelixis
  • Developer Bristol-Myers Squibb
  • Class Antihyperlipidaemics; Small molecules
  • Mechanism of Action Liver X receptor modulators
  • Discontinued Atherosclerosis; Hypercholesterolaemia

Most Recent Events

  • 04 Jun 2014 BMS 852927 is still in phase I trials for atherosclerosis and in preclinical development for hypecholesterolaemia in USA
  • 02 Aug 2013 Bristol-Myers Squibb terminates the planned phase I trial for Hypercholesterolaemia in Germany, Canada and Switzerland…

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