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Equivalent Loading of Directed Arenes in Pd(II)-Catalyzed Oxidative Cross-Coupling of Aryl C-H Bonds at Room Temperature
The unsymmetrical biaryls (Ar1-Ar2) produced by the catalytic cross-couplings of aryl halides (Ar1-halo) with aryl metallics (Ar2-M) in the loading ratio of 1:1 are popular in chemical synthesis. In contrast, there has been less precedence on the same biaryls produced effectively from two normal aryl C-H bonds with equivalent loading. Here, we report that, in a palladium/oxidant/acid catalytic system at room temperature, one arene (Ar1-H, 1 equiv) can highly selectively couple with the other one (Ar2-H, 1 equiv) to afford the target Ar1-Ar2 just by controlling the directing groups and the substituted groups on their phenyl rings. The utility of this one-one cross-coupling is also demonstrated by synthesis of a few bioactive molecules.
Mei, Chong,Zhao, Mengdi,Lu, Wenjun
p. 2714 - 2733
(2021/02/01)

Ligand Promoted Olefination of Anilides for Indirectly Introducing Fluorinated Functional Groups via Palladium Catalyst
We report a palladium-catalyzed, ligand promoted, C-H fluorine-containing olefination of anilides with 4-bromo-3,3,4,4-tetrafluorobutene as the fluorinated reagent, which has a potential transformation into other compounds due to its -CF2CF2Br functional group. -CF2CF2H was obtained by using the mild reducing agent sodium borohydride. Bioactive compounds such as aminoglutethimide derivative and propham were well-tolerated in this reaction, both of which highlight the synthetic importance of this method.
Wang, Dongjie,Xu, Xu,Zhang, Jingyu,Zhao, Yingsheng
p. 2696 - 2705
(2021/02/27)

Benzylidene succinimides as 3C synthons for the asymmetric tandem Mannich reaction/transamidation of cyclic trifluoromethyl ketimines to obtain F3C-containing polycyclic dihydroquinazolinones
By taking advantage of benzylidene succinimides as a new class of 3C synthons, a highly diastereo- and enantioselective tandem Mannich reaction/transamidation has been established by reacting them with cyclic trifluoromethylN-acyl ketimines. Using aCinchonaalkaloid-derived squaramide as the catalyst, the tandem reaction proceeded smoothly under mild conditions and afforded a range of F3C-containing chiral polycyclic dihydroquinazolinones with excellent results (up to 99% yield, all cases >20?:?1 dr, up to 99% ee).
Zhang, Xia-Yan,Dou, Pei-Hao,Lu, Wen-Ya,You, Yong,Zhao, Jian-Qiang,Wang, Zhen-Hua,Yuan, Wei-Cheng
supporting information
p. 2927 - 2930
(2021/03/23)

Meta Selective C-H Borylation of Sterically Biased and Unbiased Substrates Directed by Electrostatic Interaction
An electrostatically directed meta borylation of sterically biased and unbiased substrates is described. The borylation follows an electrostatic interaction between the partially positive and negative charges between the ligand and substrate. With this strategy, it has been demonstrated that a wide number of challenging substrates, especially 4-substituted substrates, can selectively be borylated at the meta position. Moreover, unsubstituted substrates also displayed excellent meta selectivity. The reaction employs a bench-stable ligand and proceeds at a milder temperature, precluding the need to synthesize a bulky and sophisticated ligand/template.
Chaturvedi, Jagriti,Haldar, Chabush,Bisht, Ranjana,Pandey, Gajanan,Chattopadhyay, Buddhadeb
supporting information
p. 7604 - 7611
(2021/05/26)

Nickel-Catalyzed Reductive Cross-Coupling of N-Acyl and N-Sulfonyl Benzotriazoles with Diverse Nitro Compounds: Rapid Access to Amides and Sulfonamides
Herein we report a Ni-catalyzed reductive transamidation of conveniently available N-acyl benzotriazoles with alkyl, alkenyl, and aryl nitro compounds, which afforded various amides with good yields and a broad substrate scope. The same catalytic reaction conditions were also applicable for N-sulfonyl benzotriazoles, which could undergo smooth reductive coupling with nitroarenes and nitroalkanes to afford the corresponding sulfonamides.
Bai, Jin,Li, Shangzhang,Li, Wanfang,Qu, Erdong,Zheng, Yan
supporting information

(2021/12/27)

Room temperature clickable coupling electron deficient amines with sterically hindered carboxylic acids for the construction of amides
A method for the synthesis of difficult-to-access amides was developed through the coupling of sterically hindered carboxylic acids and electron deficient amines via SO2F2-mediated dehydration. The method feathers with broad substrate scope, mild conditions, excellent functional group compatibility and high yields.
Liu, Jing,Wang, Shi-Meng,Qin, Hua-Li
supporting information

(2020/11/13)

Cu-Mediated Synthesis of Indolines and Dihydroisoquinolinones through Arylperfluoroalkylation of Unactivated Alkenes
The copper-mediated fluroalkylation/cyclization of N-allyl anilines has been described using fluoroalkyl iodides as fluoroalkylation reagents for the first time. The reaction provides an efficient and direct access to 3-fluoroalkyl indolines in moderate to good yields with unactivated double bonds as the radical acceptor. This protocol combines a simple experimental procedure with low-costing fluoroalkylated sources and excellent functional group tolerance.
Li, Dandan,Wang, Yan,Jia, Zhenzhen,Ou, Zhaocheng,Dong, Yongrui,Lv, Cunjie,Fu, Guangbin,Liang, Deqiang
p. 4797 - 4804
(2019/08/12)

Exogenous Photosensitizer-, Metal-, and Base-Free Visible-Light-Promoted C-H Thiolation via Reverse Hydrogen Atom Transfer
Visible-light-driven, intramolecular C(sp2)-H thiolation has been achieved without addition of a photosensitizer, metal catalyst, or base. This reaction induces the cyclization of thiobenzanilides to benzothiazoles. The substrate absorbs visible light, and its excited state undergoes a reverse hydrogen-atom transfer (RHAT) with 2,2,6,6-tetramethylpiperidine N-oxyl to form a sulfur radical. The addition of the sulfur radical to the benzene ring gives an aryl radical, which then rearomatizes to benzothiazole via RHAT.
Xu, Ze-Ming,Li, Hong-Xi,Young, David James,Zhu, Da-Liang,Li, Hai-Yan,Lang, Jian-Ping
supporting information
p. 237 - 241
(2019/01/10)

General rhodium-catalyzed oxidative cross-coupling reactions between anilines: Synthesis of unsymmetrical 2,2′-diaminobiaryls
Described herein is a dual chelation-assisted RhCl3-catalyzed oxidative C-H/C-H cross-coupling reaction of aniline derivatives. The highlight of this methodology is the chemo- and regioselective cross-coupling between electronically similar substrates, which represents a highly challenging task in oxidative Ar-H/Ar-H cross-coupling reactions. Furthermore, this Cp?-free catalytic reaction tolerates a range of functional groups and requires only a low molar ratio of coupling partners. These features expedite the synthesis of unsymmetrical 2,2′-diaminobiaryls.
Shi, Yang,Liu, Jiahui,Yang, Yudong,You, Jingsong
supporting information
p. 5475 - 5478
(2019/05/16)

Photocatalytic Oxidative C-H Thiolation: Synthesis of Benzothiazoles and Sulfenylated Indoles
We report studies on the photocatalytic formation of C-S bonds to form benzothiazoles via an intramolecular cyclization and sulfenylated indoles via an intermolecular reaction. Cyclic voltammetry (CV) and density functional theory studies suggest that benzothiazole formation proceeds via a mechanism that involves an electrophilic sulfur radical, while the indole sulfenylation likely proceeds via a nucleophilic sulfur radical adding into a radical cationic indole. These conditions were successfully extended to several thiobenzamides and indole substrates.
Aceves, Ernesto Millan,Albright, Samuel T.,Cedano, Mario R.,Dinh, Andrew N.,Gustafson, Jeffrey L.,Nguyen, Ashley D.,Smith, Diane K.
supporting information
p. 1648 - 1655
(2019/08/26)

Direct Amidation of Carboxylic Acids with Nitroarenes
N-Aryl amides are an important class of compounds in pharmaceutical and agrochemical chemistry. Rapid and low-cost synthesis of N-aryl amides remains in high demand. Herein, we disclose an operationally simple process to access N-aryl amides directly from readily available nitroarenes and carboxylic acids as coupling substrates. This method involves the in situ activation of carboxylic acids to acyloxyphosphonium salt for one-pot amidation, without the need for isolation of the corresponding synthetic intermediates. Furthermore, the ease of preparation and workup allow the quick and efficient synthesis of a wide range of N-aryl amides, including several amide-based druglike and agrochemical molecules.
Wang, Shao-Peng,Cheung, Chi Wai,Ma, Jun-An
p. 13922 - 13934
(2019/11/03)

Palladium(II)-Catalyzed Oxidative Homo- and Cross-Coupling of Aryl ortho -sp2 C-H Bonds of Anilides at Room Temperature
The preparation of secondary 2,2'-bisanilides has been successfully achieved through an oxidative coupling of aryl ortho-sp2 C-H bonds of anilides in the presence of catalytic Pd(OAc)2 and K2S2O8 as an oxidant in MsOH/CF3CO2H (TFA) at room temperature (25 °C). The aromatic rings of anilides substituted by various electron-donating or electron-withdrawing groups are tolerant in these coupling reactions.
Mei, Chong,Lu, Wenjun
p. 4812 - 4823
(2018/04/26)

Oxidative C?H/C?H Cross-Coupling Reactions between N-Acylanilines and Benzamides Enabled by a Cp*-Free RhCl3/TFA Catalytic System
By making use of a dual-chelation-assisted strategy, a completely regiocontrolled oxidative C?H/C?H cross-coupling reaction between an N-acylaniline and a benzamide has been accomplished for the first time. This process constitutes a step-economic and highly efficient pathway to 2-amino-2′-carboxybiaryl scaffolds from readily available substrates. A Cp*-free RhCl3/TFA catalytic system was developed to replace the [Cp*RhCl2]2/AgSbF6 system generally used in oxidative C?H/C?H cross-coupling reactions between two (hetero)arenes (Cp=pentamethylcyclopentadienyl, TFA=trifluoroacetic acid). The RhCl3/TFA system avoids the use of the expensive Cp* ligand and AgSbF6. As an illustrative example, the procedure developed herein greatly streamlines the total synthesis of the naturally occurring benzo[c]phenanthridine alkaloid oxynitidine, which was accomplished in excellent overall yield.
Shi, Yang,Zhang, Luoqiang,Lan, Jingbo,Zhang, Min,Zhou, Fulin,Wei, Wenlong,You, Jingsong
supporting information
p. 9108 - 9112
(2018/07/25)

Synthetic method of efavirenz key intermediate
The invention provides a synthetic method of an efavirenz key intermediate. The synthetic method comprises the following steps: carrying out reaction on parachloroaniline and pivaloyl chloride to protect amino to obtain N-(4-chlorphenyl)-2,2-dimethyl propanamide; carrying out Friedel-Crafts acylation reaction on the product and Friedel-Crafts acylation under action of aluminum trichloride to hydrolyze to obtain 4-chloro-2-trifluoroacetyl aniline hydrochloride in an acidic condition; and then carrying out alkalization to obtain 4-chloro-2-trifluoroacetyl aniline, carrying out reaction with cyclopropyl acetylene magnesium chloride in a catalytic system formed by a ligand (1R, 2S)-1-phenyl-2-(1-pyrrolidyl)-1-propyl alcohol, and carrying out an asymmetrical self-catalytic reaction to obtain the efavirenz key intermediate. The synthetic method of the efavirenz key intermediate, provided by the invention, is cheap and easily available in raw material, low in toxicity of reagent and mild in reaction condition, amino protection and deprotection are not carried out frequently, the line is concise, the yields of reaction of each step are excellent, and the total yield is high.
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Paragraph 0018

(2019/01/08)

Rhodium(III)-catalysed, redox-neutral C(sp2)-H alkenylation using pivalimide as a directing group with internal alkynes
In the presence of [RhCp?Cl2]2, N-pivaloyl anilines react with internal alkynes to give the corresponding 2-alkenylpivalimides under redox neutral conditions through C-H activation. This redox neutral hydroarylation, which does not require an external organic acid, unlocks a regioselective synthetic route to 2-alkenyl anilines and is generally applicable to diversely substituted electron rich and electron poor pivalimides.
Kathiravan, Subban,Nicholls, Ian A.
supporting information
p. 1 - 4
(2016/12/23)

A unified strategy for silver-, base-, and oxidant-free direct arylation of C-H bonds
Here, we report a dual catalytic approach for room temperature direct arylation of C-H bonds with aryldiazonium salts as a simple aryl group donor, also working as an internal oxidant via C-N2 bond cleavage. This unified strategy has been achieved by the synergistic combination of visible-light metal-free photoredox and palladium catalysis under silver-, base- and/or additive-free conditions. The broad substrate scope, functional group tolerance, excellent regioselectivity and redox-neutral conditions of this process make it attractive for the effective synthesis of a wide range of important N-heterocyclic commodities such as dibenzo[b,d]azepine, carbazole and phenanthridine.
Sahoo, Manoj K.,Midya, Siba P.,Landge, Vinod G.,Balaraman, Ekambaram
supporting information
p. 2111 - 2117
(2017/07/24)

Insights into the Mechanism of Anodic N-N Bond Formation by Dehydrogenative Coupling
The electrochemical synthesis of pyrazolidine-3,5-diones and benzoxazoles by N-N bond formation and C,O linkage, respectively, represents an easy access to medicinally relevant structures. Electrochemistry as a key technology ensures a safe and sustainabl
Gieshoff, Tile,Kehl, Anton,Schollmeyer, Dieter,Moeller, Kevin D.,Waldvogel, Siegfried R.
p. 12317 - 12324
(2017/09/12)

Rhodium-Catalyzed oxidative amidation of sterically hindered aldehydes and alcohols
A rhodium-catalyzed oxidative amidation reaction has been developed with sterically hindered aldehydes and alcohols for the synthesis of amides containing a quaternary carbon at the α position. A variety of amine nucleophiles, both aliphatic and aromatic, are employed and afford the corresponding amides in good to excellent yields. Finally, mechanistic studies are performed to gain insight into both catalytic cycles.
Nguyen, Trang T.,Hull, Kami L.
p. 8214 - 8218
(2018/05/23)

Preparation method of 4-chloro-2-(trifluoroacetyl) aniline hydrochloride hydrate
The invention discloses a preparation method of a 4-chloro-2-(trifluoroacetyl) aniline hydrochloride hydrate and belongs to the field of compound synthesis. The method adopts parachloroaniline as a raw material and comprises steps as follows: 1, parachlor
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Paragraph 0006; 0018; 0022; 0026; 0030

(2016/11/21)

Palladium-Catalysed Synthesis of α-(Trifluoromethyl)styrenes by Means of Directed C-H Bond Functionalization
We report the first introduction of 2-bromo-3,3,3-trifluoropropene (BTP) by directed C-H bond functionalization. The developed method gives straightforward access to α-(trifluoromethyl)styrene derivatives without prior prefunctionalization of the substrates. This palladium-catalysed transformation was applied to a broad range of substrates, and the corresponding trifluoromethylated products were obtained in good yields. This approach represents an alternative pathway to the classical method previously used to access such molecules.
Zhao, Qun,Besset, Tatiana,Poisson, Thomas,Bouillon, Jean-Philippe,Pannecoucke, Xavier
p. 76 - 82
(2016/01/26)

Amine Activation: Synthesis of N-(Hetero)arylamides from Isothioureas and Carboxylic Acids
A novel method for N-(hetero)arylamide synthesis based on rarely explored amine activation, rather than classical acid activation, is reported. The activated amines are easily prepared using a three-component reaction with commercial reagents. The new method shows a broad scope including challenging amides not (efficiently) accessible via classical protocols.
Zhu, Yan-Ping,Sergeyev, Sergey,Franck, Philippe,Orru, Romano V. A.,Maes, Bert U. W.
supporting information
p. 4602 - 4605
(2016/09/28)

AN IMPROVED PROCESS FOR THE PREPARATION OF A NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR
The present invention relates to an improved process for the preparation of a non-nucleoside reverse transcriptase inhibitor. Specifically, the present invention relates to an improved process for the preparation of Efavirenz of Formula 1. The present invention also relates to a process for the preparation of compound of Formula 2, an intermediate used in the preparation of Efavirenz, wherein X is a halogen atom; X1 is a leaving group.
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Page/Page column 9

(2015/09/22)

Imidazolium Salt Catalyzed para -Selective Halogenation of Electron-Rich Arenes
A highly para-selective halogenation of arenes bearing coordinating groups in the presence of a dimidazolium salt as a catalyst is reported. A series of electron-rich p-haloarenes were prepared in good yields and good to excellent selectivities. We also propose a plausible mechanism for the catalytic reaction.
Chen, Jie,Xiong, Xiaoyu,Chen, Zenghua,Huang, Jianhui
supporting information
p. 2831 - 2834
(2015/12/18)

PROPHYLACTIC OR THERAPEUTIC METHOD FOR SJOGREN'S SYNDROME
The present invention provides a prophylactic or therapeutic agent and a prophylactic or therapeutic method superior in the prophylaxis or treatment of Sjogren's syndrome. Provided are a prophylactic or therapeutic agent for Sjogren's syndrome, containing
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Paragraph 0106; 0107

(2014/06/23)

CuCl-catalyzed ortho trifluoromethylation of arenes and heteroarenes with a pivalamido directing group
The CuCl catalyzed direct trifluoromethylation of sp2 C-H bonds has been realized, using the Togni reagent as the CF3 source. This reaction achieves the goal of regio-selectively converting C-H into C-CF 3 with ecological and readily available starting materials.
Cai, Shangjun,Chen, Chao,Sun, Zelin,Xi, Chanjuan
supporting information
p. 4552 - 4554
(2013/06/04)

Discovery of a new 2-aminobenzhydrol template for highly potent squalene synthase inhibitors
To obtain small and efficient squalene synthase inhibitors, a flexible 2-aminobenzhydrol open form structure was designed and showed potent inhibitory activity comparable to 4,1-benzoxazepin compounds. Further chemical modification led to the discovery of a novel template with a strong squalene synthase inhibitory activity, and its basic structure-activity relationship was revealed. The X-ray crystallographic data of compound 12 bound to the active site of squalene synthase provided an important insight into the binding mode of this alternative template that formed 11-membered ring conformations with an intramolecular hydrogen bond.
Ichikawa, Masanori,Yokomizo, Aki,Itoh, Masao,Sugita, Kazuyuki,Usui, Hiroyuki,Shimizu, Hironari,Suzuki, Makoto,Terayama, Koji,Kanda, Akira
experimental part
p. 1930 - 1949
(2011/05/03)

Trifluoromethyl-promoted homocamptothecins: Synthesis and biological activity
The homocamptothecin (hCPT) represents a new class of topoisomerase inhibitor which combines enhanced plasma stability and strong antitumor activity. Fluorine imparts desirable characteristics to drugs by modulating both the pharmacokinetics and pharmacodynamic properties of a drug. Therefore, in an attempt to improve the antitumor activity of homocamptothecins, seven new 7-trifluoromethylated homocamptothecin derivatives were prepared by proline-catalyzed Friedlander annulation. The antitumor activity in vitro and in vivo on cancer cell lines, and inhibitory properties of topoisomerase I-mediated DNA cleavage of compounds 6c and 8b were evaluated. Several of these trifluoromethylated hCPT derivatives (such as 6a, 6b and 6c) possessed higher in vitro antitumor activity than topotecan (TPT). Especially, the compound 6c showed effective in vivo antitumor activity comparable to that of TPT.
Zhu, Lingjian,Miao, Zhenyuan,Sheng, Chunquan,Guo, Wei,Yao, Jianzhong,Liu, Wenfeng,Che, Xiaoying,Wang, Wenya,Cheng, Pengfei,Zhang, Wannian
experimental part
p. 2726 - 2732
(2010/08/07)

An alternative route for synthesis of o-trifluoroacetylanilines as useful fluorine-containing intermediates
A series of o-trifluoroacetyl aniline derivatives were synthesized in three steps. In this method, we first utilized trifluoroacetic anhydride to introduce trifluoroacetyl group to the ortho position of aniline with higher yield than that of some previously reported methods. In addition, the procedure is shown to be highly regiospecific. This type of compounds can be used as the key intermediates in the preparation of a variety of inhibitors of HIV reverse transcriptase which is an important pharmacological target of many anti-AIDS agents.
Zhu, Lingjian,Miao, Zhenyuan,Sheng, Chunquan,Yao, Jianzhong,Zhuang, Chunlin,Zhang, Wannian
experimental part
p. 800 - 804
(2010/09/04)

Substituted Nitrogen Heterocycles and Synthesis and Uses Thereof
The invention relates to a nitrogen heterocycle compound of formula 1: Also disclosed are a method of synthesizing the compound and use of the compound for treating various diseases and conditions.
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Page/Page column 27

(2009/10/06)

INDOLES USEFUL IN THE TREATMENT OF INFLAMATION
There is provided compounds of formula (I), Wherein T, Y, X1 , R1, R2, R3, R4 and R5 have meanings given in the description, and pharmaceutically-acceptable salts thereof, which compounds are useful in the treatment of diseases in which inhibition of the activity of a member of the MAPEG family is desired and/or required, and particularly in the treatment of inflammation.
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Page/Page column 114

(2008/06/13)

CHEMICAL COMPOUNDS
The use of a compound of formula I, Y is a single bond, C=O, C=S or S(O)m where m is 0, 1 or 2; the ring is a 6 membered oaromatic ring or is a 5 or 6 membered heteroaromatic ring; Z and Z' are =C- or -N- provided that both are not N; R1/
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Page/Page column 127

(2008/06/13)

RECEPTOR ANTAGONIST
An agent for modulating the function of an RFRP receptor, characterized by containing either a compound represented by the formula (I) [wherein ring A represents an optionally substituted aromatic ring; ring B represents an optionally substituted benzene
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Page/Page column 52

(2008/06/13)

HIGHLY SELECTIVE NOVEL AMIDATION METHOD
The present invention provides an industrial production method with a short process having a high yield of an aliphatic cyclic carboxamide having carboxyl group, which comprises reacting functional group-selectively using an inexpensive condensing agen
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Page/Page column 30-31

(2010/02/15)

RECEPTOR AGONISTS
The present invention provides a TGR5 receptor agonist comprising a fused ring compound represented by the formula wherein ring A is an optionally substituted aromatic ring; and ring B' is a 5- to 8-membered ring having one or more substituents or a salt
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Page/Page column 89

(2008/06/13)

Bis-aryl sulfonamides
Compounds are provided that act as potent antagonists of chemokine receptors. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of chemokine receptor-mediated diseases, and as controls in assays for the identification of chemokine antagonists.
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(2008/06/13)

Infrared spectra of N-aryl substituted amides 2/4-XC6H 4NHCOR (R = H, CH3-iXi, C6H 5 or C6H5Cl; X = H, Cl or CH3 and i = 0, 1, 2 or 3)
Several N-(aryl)-substituted amides of the general formula, 2/4-XC 6H4NHCOR (where X = H, Cl or CH3 and R = H, CH3, CH2CH3, CH(CH3)2, C(CH3)3, C6H5 or C6H 5Cl) are prepared, characterised and their infrared spectra measured in the solid state and analysed. Generally chloro substitution in the side chain increases the C=O absorptions, while that of methyl groups lower the wave numbers. Amides with trimethyl substituted side chains absorb at higher wavenumbers. But the N-H and C-N stretching vibrations do not show particular trends on side chain substitution. This may be due to the fact that the spectra were recorded in the solid state and the compounds may crystallise in different forms in the solid state. The intercorrelations of C=O and N-H absorption frequencies of all the amides have been made. The correlations are reasonably linear with some exceptions for the reasons stated above.
Gowda, B. Thimme,Jyothi,Jayalakshmi,Damodara
p. 564 - 568
(2007/10/03)

ARYL SULFONAMIDES
Compounds are provided that act as potent antagonists of the CCR9 receptor, and which have been further confirmed in animal testing for inflammation, one of the hallmark disease states for CCR9. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR9-mediated diseases, and as controls in assays for the identification of CCR9 antagonists.
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Page 52-53

(2008/06/13)

Crystalline Efavirenz
The potent reverse transcriptase inhibitor Efavirenz is produced in crystalline form. Crystalline Efavirenz exists in several physical forms which are-designated Forms 1, 2, 3 and 4, and are characterized by x-ray powder diffraction and differential scanning calorimetry. Pharmaceutical compositions and methods are useful for the treatment of the human immunodeficiency virus (HIV).
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(2008/06/13)

CCR9 INHIBITORS AND METHODS OF USE THEREOF
The invention relates to compounds represented by Structural Formula I, which can bind to CCR9 receptors and block the binding of a ligand (e.g., TECK) to the receptors. The invention also relates to a method of inhibiting a function of CCR9, and to the use compounds represented by Structural Formula I in research, therapeutic, prophylactic and diagnostic methods.
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Page 74-75

(2008/06/13)

Cyclizations of substituted benzylidene-3-alkenylamines: Synthesis of the tricyclic core of the martinellines
The martinellines (1 and 2) are natural products that possess both interesting biological activity and chemical structure. During the investigation of a hetero Diels-Alder route to these molecules, alternate Lewis acid-dependent cyclizations of (2'-amino-N'-tert-butoxycarbonyl-5'- chlorobenzylidene)-3-butenylamine (10) were observed. The reaction of a variety of imines with TMSOTf or TiCl4 led to the formation of different heterocycles including iminodibenzo[b,f][1,5]diazocines, hexahydropyrido[1,2- c]quinazolin-6-ones, tetrahydropyrrolo[1,2-c]quinazolin-5-ones, 2- arylpiperidines, and 2-arylpyrrolidines. Tetrahydropyrrolo[1,2-c]quinazolin- 5-one 54, obtained via this new methodology, was used as an intermediate in the synthesis of the tricyclic ring system (65) of the martinellines.
Frank, Kristine E.,Aube, Jeffrey
p. 655 - 666
(2007/10/03)

Synthesis of cyclopropylacetylene
The present invention relates generally to novel methods for the synthesis of cyclopropylacetylene which is a reagent in the asymmetric synthesis of (S)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one which is a useful human immunodeficiency virus (HIV) reverse transcriptase inhibitor.
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(2008/06/13)

Asymmetric synthesis of benzoxazinones
The present invention provides novel methods for the asymmetric synthesis of (S)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one of formula (VI-i) STR1 which is useful as a human immunodeficiency virus (HIV) reverse transcriptase inhibitor.
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(2008/06/13)

Asymmetric synthesis of benzoxazinones
The present invention provides novel methods for the asymmetric synthesis of (S)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one of formula (VI-i) STR1 which is useful as a human immunodeficiency virus (HIV) reverse transcriptase inhibitor.
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(2008/06/13)

Practical asymmetric synthesis of Efavirenz (DMP 266), an HIV-1 reverse transcriptase inhibitor
A highly enantioselective and practical synthesis of the HIV-1 reverse transcriptase inhibitor efavirenz (1) is described. The synthesis proceeds in 62% overall yield in seven steps from 4-chloroaniline (6) to give efavirenz (1) in excellent chemical and optical purity. A novel, enantioselective addition of Li-cyclopropyl acetylide (4a) to p-methoxybenzyl-protected ketoaniline 3a mediated by (1R,2S)-N-pyrrolidinylnorephedrine lithium alkoxide (5a) establishes the stereogenic center in the target with a remarkable level of stereocontrol.
Pierce, Michael E.,Parsons Jr., Rodney L.,Radesca, Lilian A.,Lo, Young S.,Silverman, Stuart,Moore, James R.,Islam, Qamrul,Choudhury, Anusuya,Fortunak, Joseph M. D.,Nguyen, Dieu,Luo, Chi,Morgan, Susan J.,Davis, Wayne P.,Confalone, Pat N.,Chen, Cheng-Yi,Tillyer, Richard D.,Frey, Lisa,Tan, Lushi,Xu, Feng,Zhao, Dalian,Thompson, Andrew S.,Corley, Edward G.,Grabowski, Edward J. J.,Reamer, Robert,Reider, Paul J.
p. 8536 - 8543
(2007/10/03)

Synthesis of 6-chloro 2(-ethylamino)-4-methyl-4-phenyl-[-4-14c]-4h,- 3,1-benzoxazine (etifoxine)
Carbonation of phenyl lithium with 14CO2, followed by reduction of [14CO2] benzoic acid, led to [α-14C] benzyl alcohol 3, the oxidation of which afforded the [α-14C] benzaldehyde 4. The lat
Azim, Elmostafa,Dupuy, Jean Michel,Lepage, Francis,Veyre, Annie,Madelmont, Jean Claude
p. 907 - 914
(2007/10/03)

Synthesis of cyclopropylacetylene
An improved synthesis of cyclopropylacetylene involving cyclization of 5-halo-1-pentyne in strong base is disclosed, and is useful for preparing compounds with a cyclopropylethynyl substituent, such as an intermediate for a highly potent HIV reverse transcriptase inhibitor or other pharmaceutically active compounds.
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(2008/06/13)

Benzoxazinones as inhibitors of HIV reverse transcriptase
Certain benzoxazinones are useful in the inhibition of HIV reverse transcriptase (including its resistant varieties), the prevention or treatment of infection by HIV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.
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(2008/06/13)

L-743,726 (DMP-266): A novel, highly potent nonnucleoside inhibitor of the human immunodeficiency virus type 1 reverse transcriptase
The clinical benefit of the human immunodeficiency virus type 1 (HIV-1) nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) is limited by the rapid selection of inhibitor-resistant vital variants. However, it may he possible to enhance the clinical utility of this inhibitor class by deriving compounds that express both high levels of antiviral activity and an augmented pharmacokinetic profile. Accordingly, we developed a new class of NNRTIs, the 1,4-dihydro-2H-3,1-benzoxazin-2-ones. L-743,726 (DMP-266), a member of this class, was chosen for clinical evaluation because of its in vitro properties. The compound was a potent inhibitor of the wild-type HIV-1 RT (K(i) = 2.93 nM) and exhibited a 95% inhibitory concentration of 1.5 nM for the inhibition of HIV-1 replicative spread in cell culture. In addition, L-743,726 was found to be capable of inhibiting, with 95% inhibitory concentrations of ≤1.5 μM, a panel of NNRTI-resistant mutant viruses, each of which expressed a single RT amino acid substitution. Derivation of virus with notably reduced susceptibility to the inhibitor required prolonged cell culture selection and was mediated by a combination of at least two RT amino acid substitutions. Studies of L-743,726 in rats, monkeys, and a chimpanzee demonstrated the compound's potential for good oral bioavailability and pharmacokinetics in humans.
Young,Britcher,Tran,Payne,Lumma,Lyle,Huff,Anderson,Olsen,Carroll,Pettibone,O'Brien,Ball,Balani,Lin,Chen,Schleif,Sardana,Long,et al.
p. 2602 - 2605
(2007/10/03)