(3R,5R)-3,5-dihydroxy-7-(5-(isobutyramidomethyl)-2- oxooxazolidin-3-yl)heptanoic acid

(3R,5R)-3,5-dihydroxy-7-(5-(isobutyramidomethyl)-2- oxooxazolidin-3-yl)heptanoic acid

   

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udgir, maharashtra, india

Udgir

City in India

Udgir is a city with a municipal council in Latur district in the Indian state of Maharashtra. It is located in the Marathwada division of the state. It is also the headquarters for the Udgir subdivision and Udgir Taluka.Wikipedia

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(3R,5R)-3,5-dihydroxy-7-(5-(isobutyramidomethyl)-2- oxooxazolidin-3-yl)heptanoic acid

(3R,5R)-3,5-dihydroxy-7-(5-(isobutyramidomethyl)-2- oxooxazolidin-3-yl)heptanoic acid

   

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udgir, maharashtra, india

Udgir

City in India

Udgir is a city with a municipal council in Latur district in the Indian state of Maharashtra. It is located in the Marathwada division of the state. It is also the headquarters for the Udgir subdivision and Udgir Taluka.Wikipedia

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1-chloro-4-(3,5-dichloropent-1-ynyl)benzene

1-chloro-4-(3,5-dichloropent-1-ynyl)benzene (3ci) :

Following general procedure, The product was purified by flash column chromatography on silica gel (petroleum ether) and 1c : 2i = 1:53, obtained in 61 % yield as a pale yellow oil (29.9 mg).

1H NMR (600 MHz, CDCl3) δ 7.37 (t, J = 10.3 Hz, 2H), 7.31 (d, J = 8.2 Hz, 2H), 5.00 (t, J = 6.8 Hz, 1H), 3.78 (ddd, J = 16.9, 10.1, 4.7 Hz, 2H), 2.47 (q, J = 6.5 Hz, 2H).

13C NMR (151 MHz, CDCl3) δ 135.1, 133.0, 128.7, 120.2, 86.9, 85.6, 45.9, 41.4, 40.8.

HRMS calcd for C11H9Cl3 [M + H]+ 245.9770; found: 245.9772.

Directed alkynylation of unactivated C(sp3)-H bonds with ethynylbenziodoxolones mediated by DTBP

Green Chem., 2016, 18,4185-4188

DOI: 10.1039/C6GC01336H, Communication

Zhi-Fei Cheng, Yi-Si Feng, Chun Rong, Tao Xu, Peng-Fei Wang, Jun Xu, Jian-Jun Dai, Hua-Jian Xu
A general and efficient alkynylation of unactivated C(sp³)-H bonds under metal-free conditions was developed herein.

Directed alkynylation of unactivated C(sp³)–H bonds with ethynylbenziodoxolones mediated by DTBP

Zhi-Fei Cheng,^a   Yi-Si Feng,*^abc   Chun Rong,^a   Tao Xu,^a  Peng-Fei Wang,^a   Jun Xu,^a   Jian-Jun Dai^a and   Hua-Jian Xu*^abc  

*Corresponding authors

^aSchool of Chemistry and Chemical Engineering, School of Biological and Medical Engineering, Hefei University of Technology, Hefei 230009, P. R. China

^bAnhui Key Laboratory of Controllable Chemical Reaction and Material Chemical Engineering, Hefei 230009, P. R. China
E-mail: hjxu@hfut.edu.cn
Fax: (+86)-551-62904405

^cAnhui Provincial Laboratory of Heterocyclic Chemistry, Maanshan 243110, China

Green Chem., 2016,18, 4185-4188

DOI: 10.1039/C6GC01336H, http://pubs.rsc.org/en/Content/ArticleLanding/2016/GC/C6GC01336H?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

A general and efficient method for the direct alkynylation of unactivated C(sp³)–H bonds under metal-free conditions is described. The reaction performs smoothly under mild conditions and shows excellent functional-group tolerance. Initial mechanistic investigation indicates that the reaction may involve a radical pathway.

 

//////////Directed alkynylation, unactivated C(sp3)-H bonds,  ethynylbenziodoxolones,  DTBP

Directed alkynylation of unactivated C(sp3)-H bonds with ethynylbenziodoxolones mediated by DTBP

Directed alkynylation of unactivated C(sp3)-H bonds with ethynylbenziodoxolones mediated by DTBP

Green Chem., 2016, 18,4185-4188

DOI: 10.1039/C6GC01336H, Communication

Zhi-Fei Cheng, Yi-Si Feng, Chun Rong, Tao Xu, Peng-Fei Wang, Jun Xu, Jian-Jun Dai, Hua-Jian Xu
A general and efficient alkynylation of unactivated C(sp³)-H bonds under metal-free conditions was developed herein.

Directed alkynylation of unactivated C(sp³)–H bonds with ethynylbenziodoxolones mediated by DTBP

Zhi-Fei Cheng,^a   Yi-Si Feng,*^abc   Chun Rong,^a   Tao Xu,^a  Peng-Fei Wang,^a   Jun Xu,^a   Jian-Jun Dai^a and   Hua-Jian Xu*^abc  

*Corresponding authors

^aSchool of Chemistry and Chemical Engineering, School of Biological and Medical Engineering, Hefei University of Technology, Hefei 230009, P. R. China

^bAnhui Key Laboratory of Controllable Chemical Reaction and Material Chemical Engineering, Hefei 230009, P. R. China
E-mail: hjxu@hfut.edu.cn
Fax: (+86)-551-62904405

^cAnhui Provincial Laboratory of Heterocyclic Chemistry, Maanshan 243110, China

Green Chem., 2016,18, 4185-4188

DOI: 10.1039/C6GC01336H, http://pubs.rsc.org/en/Content/ArticleLanding/2016/GC/C6GC01336H?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

A general and efficient method for the direct alkynylation of unactivated C(sp³)–H bonds under metal-free conditions is described. The reaction performs smoothly under mild conditions and shows excellent functional-group tolerance. Initial mechanistic investigation indicates that the reaction may involve a radical pathway.

 

2-((4-chlorophenyl)ethynyl)tetrahydrofuran (3cg) ref 1 : Following general procedure, The product was purified by flash column chromatography on silica gel (petroleum ether) and 1c : 2g = 1:69, obtained in 70 % yield as a pale yellow oil (28.8 mg).

 

1H NMR (600 MHz, CDCl3) δ 7.35 (d, J = 8.4 Hz, 2H), 7.28 – 7.25 (m, 2H), 4.82 – 4.77 (m, 1H), 4.00 (dd, J = 14.6, 7.1 Hz, 1H), 3.85 (dd, J = 13.6, 7.8 Hz, 1H), 2.26 – 2.19 (m, 1H), 2.11 – 2.04 (m, 2H), 1.95 (dd, J = 13.3, 5.8 Hz, 1H).

 

 

 

13C NMR (151 MHz, CDCl3) δ 134.2, 132.9, 128.5, 121.2, 90.0, 83.3, 68.5, 67.9, 33.3, 25.4.

//////////Directed alkynylation, unactivated C(sp3)-H bonds,  ethynylbenziodoxolones,  DTBP

THREO ERYTHRO ISOMERS EXAMPLES

 

(5 R*,1′R*)-5-[3,5-Di-tert-butyl-4-hydroxyphenyl)hydroxymethyl]-2-ethyl-1,2-isothiazolidine-1,1-dioxide 12a (threo) and (5S*,1′R*)-5-[3,5-Di-tert-butyl-4-hydroxyphenyl)hydroxymethyl]-2-ethyl-1,2-isothiazolidine-1,1-dioxide 12b (erythro)

Compound 12a: mp 160−162 °C. 1H NMR (500 MHz, (CDCl3 δ) 1.25 (t, J = 7.3 Hz, 3H), 1.43 (s, 18H), 1.84 (m, 1H), 1.94 (m, 1H), 3.03 (ddd,J = 9.1, 8.2, 7.2 Hz, 1H), 3.08 (dq, J = 13.4, 7.2 Hz, 1H), 3.18 (ddd, J = 9.1, 8.0, 3.5 Hz, 1H), 3.23 (dq, J = 13.4, 7.2 Hz, 1H), 3.53 (m, 1H), 4.84 (d, J = 9.7 Hz 1H), 5.27 (s, 1H), 7.16 (s, 2H). 13C NMR (150 MHz, (CDCl3 δ) 13.18, 23.09, 30.24, 34.41, 39.42, 43.92, 63.67, 74.64, 123.58, 129.99, 136.38, 154.22. Elemental analysis: Calcd for C20H33O4NS: C; 62.63, H; 8.67, N; 3.65, S; 8.36, Found: C; 62.58, H; 8.62, N; 3.66, S; 8.32. Compound 12b: mp 78−96 °C. 1H NMR (500 MHz, (CDCl3 δ) 1.25 (t, J = 7.3 Hz, 3H), 1.44 (s, 18H), 2.08 (m, 1H), 2.60 (dq, J = 13.0, 8.5 Hz, 1H), 3.07 (m, 1H), 3.08 (m, 1H), 3.21 (dq, J = 13.3, 7.2 Hz, 1H), 3.28 (m, 1H), 3.31 (d, J = 2.6 Hz, 1H), 3.38 (td, J = 8.5, 2.1 Hz 1H), 5.21 (s, 1H), 5.40 (brs, 1H), 7.15 (s, 2H). 13C NMR (150 MHz, (CDCl3 δ) 13.18, 18.30, 30.28, 34.43, 39.46, 44.56, 63.21, 69.19, 122.41, 129.94, 136.14, 153.54. Elemental analysis: Calcd for C20H33O4NS: C; 62.63, H; 8.67, N; 3.65, S; 8.36, Found. C; 62.19, H; 8.63, N; 3.62, S; 8.10.

PAPER

Development of One-Pot Synthesis of New Antiarthritic Drug Candidate S-2474 with High E-Selectivity

Katsuo Oda^†, Takemasa Hida*^†, Teruo Sakata^‡, Masahiko Nagai^‡, Yoshihide Sugata^‡, Toshiaki Masui^† and Hideo Nogusa^†

Chemical Development Department, CMC Development Laboratories, Shionogi & Co., Ltd., 1-3, Kuise Terajima 2-chome, Amagasaki, Hyogo 660-0813, Japan, and Shionogi Research Laboratories, Shionogi & Co., Ltd., 12-4, Sagisu 5-chome, Fukushima-ku, Osaka 553-0002, Japan

Org. Process Res. Dev., 2008, 12 (3), pp 442–446

DOI: 10.1021/op800008w

 

 http://pubs.acs.org/doi/full/10.1021/op800008w

* To whom correspondence should be addressed. Telephone: +81-6-6401-8198 . Fax: +81-6-6401-1371. E-mail:takemasa.hida@shionogi.co.jp., †

Chemical Development Department, CMC Development Laboratories.

, ‡Shionogi Research Laboratories.

A one-pot synthesis of S-2474 was developed to overcome the problems of a large number of steps, low stereoselectivity, low yield, a large amount of waste, and severe reaction conditions. Aldol-type condensation of 3,5-di-tert-butyl-4-hydroxybenzaldehyde and N-ethyl-γ-sultam was carried out with LDA and then quenched with water. Dehydration proceeded under basic conditions, providing S-2474 directly as a single isomer on the benzylidene double bond. The reaction mechanism appears to involve a quinone methide intermediate. Environmental assessment of the development of this compound is also discussed in this paper.

?///////New,  Antiarthritic , Drug Candidate,  S-2474, Shionogi Research Laboratories, cyclooxygenase-2,  (COX-2),  5-lipoxygenase , (5-LO),

• Supporting Info

5-Fluoro-2-(4-(methylsulfonyl)-phenyl)pyridine

5-Fluoro-2-(4-(methylsulfonyl)-phenyl)pyridine

1H NMR (400 MHz, DMSO-d6) δ 8.73 (d, J = 2.8 Hz, 1H), 8.31 (bd, J = 8.8 Hz, 2H), 8.20 (dd, J = 8.8, 4.3 Hz, 1H), 8.04 (bd, J = 8.5 Hz, 2H), 7.91 (td, J = 8.8, 3.0 Hz, 1H), 3.27 (s, 3H). 

13C (100.6 MHz, DMSO-d6) 158.3, 151.3, 142.7, 141.3, 138.4, 128.0, 127.8, 125.0, 124.8, 123.3, 123.2, 44.0. 

HRMS calcd for C12H11FNO2S (M + H)+ 252.0489, found, 252.0485.

Paper

Development of Large-Scale Routes to Potent GPR119 Receptor Agonists

Richard T. Matsuoka*†, Eric E. Boros#, Andrew D. Brown†, Kae M. Bullock†, Will L. Canoy‡, Andrew J. Carpenter#, Jeremy D. Cobb†,Shannon E. Condon†, Nicole M. Deschamps†, Vassil I. Elitzin†, Greg Erickson†,Jing M. Fang#, David H. Igo§, Biren K. Joshi‡, Istvan W. Kaldor#, Mark B. Mitchell†, Gregory E. Peckham#, Daniel W. Reynolds‡, Matthew C. Salmon†, Matthew J. Sharp†, Elie A. Tabet#, Jennifer F. Toczko†, Lianming Michael Wu‡, and Xiao-ming M. Zhou†

†API Chemistry Department, ‡Analytical Science & Development Department, #Medicinal Chemistry Department, and§Particle Sciences and Engineering Department, GlaxoSmithKline, 709 Swedeland Road, King of Prussia, Pennsylvania 19406, United States

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.6b00157, http://pubs.acs.org/doi/abs/10.1021/acs.oprd.6b00157

Publication Date (Web): July 13, 2016

Copyright © 2016 American Chemical Society

*E-mail: richard.t.matsuoka@gsk.com.

Abstract

Practical and scalable syntheses were developed that were used to prepare multikilogram batches of GSK1292263A (1) and GSK2041706A (15), two potent G protein-coupled receptor 119 (GPR119) agonists. Both syntheses employed relatively cheap and readily available starting materials, and both took advantage of an SNAr synthetic strategy.

• Supporting Info

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