450-88-4Relevant academic research and scientific papers
Preparative scale synthesis of the biaryl core of anacetrapib via a ruthenium-catalyzed direct arylation reaction: Unexpected effect of solvent impurity on the arylation reaction
Ouellet, Stephane G.,Roy, Amelie,Molinaro, Carmela,Angelaud, Remy,Marcoux, Jean-Francois,OShea, Paul D.,Davies, Ian W.
, p. 1436 - 1439 (2011)
In this report, we disclose our findings regarding the remarkable effect of a low-level impurity found in the solvent used for a ruthenium-catalyzed direct arylation reaction. This discovery allowed for the development of a robust and high-yield arylation protocol that was demonstrated on a multikilogram scale using carboxylate as the cocatalyst. Finally, a practical, scalable, and chromatography-free synthesis of the biaryl core of Anacetrapib is described.(Figure Presented)
Transition-metal-free decarboxylative bromination of aromatic carboxylic acids
Quibell, Jacob M.,Perry, Gregory J. P.,Cannas, Diego M.,Larrosa, Igor
, p. 3860 - 3865 (2018/04/26)
Methods for the conversion of aliphatic acids to alkyl halides have progressed significantly over the past century, however, the analogous decarboxylative bromination of aromatic acids has remained a longstanding challenge. The development of efficient methods for the synthesis of aryl bromides is of great importance as they are versatile reagents in synthesis and are present in many functional molecules. Herein we report a transition metal-free decarboxylative bromination of aromatic acids. The reaction is applicable to many electron-rich aromatic and heteroaromatic acids which have previously proved poor substrates for Hunsdiecker-type reactions. In addition, our preliminary mechanistic study suggests that radical intermediates are not involved in this reaction, which is in contrast to classical Hunsdiecker-type reactivity. Overall, the process demonstrates a useful method for producing valuable reagents from inexpensive and abundant starting materials.
INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL
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Paragraph 0166; 0168, (2016/10/06)
The present invention provides compounds of Formula Ia and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and conditions associated with excessive salt and water retention.
Preparation method of Anacetrapib key intermediate
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, (2017/04/25)
The invention relates to a preparation method of an Anacetrapib key intermediate 1-bromo-4-fluoro-5-isopropyl-2-methoxybenzene. The preparation method comprises the following steps: hydrolyzing an initial raw material 2,4-difluoronitrobenzene to obtain 4-fluoro-2-hydroxynitrobenzene, methylating 4-fluoro-2-hydroxynitrobenzene to obtain 4-fluoro-2-methoxynitrobenzene, carrying out nitro group reduction to form 4-fluoro-2-methoxyaniline, carrying out diazo bromination to obtain 4-fluoro-2-methoxybromobenzene, carrying out Friedel-Crafts acylation to obtain 2-fluoro-4-methoxy-5-bromoacetophenone, carrying out a condensation reaction to obtain 2-(2-fluoro-4-methoxy-5-bromophenyl)-propane-2-ol, carrying out an elimination reaction to obtain 1-bromo-4-fluoro-2-methoxy-5-(1-methylvinyl)benzene, and hydrogenating the 1-bromo-4-fluoro-2-methoxy-5-(1-methylvinyl)benzene to obtain 1-bromo-4-fluoro-5-isopropyl-2-methoxybenzene. The preparation method has the advantages of realization of low cost, good quality and high yield of the above final product, mild reaction conditions, simplicity in operation, and easiness in industrialization.
Chemical Compounds
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Paragraph 0505; 0506, (2014/06/25)
The present invention relates to imidazopyridazine derivatives. More particularly, it relates to 4-(biphenyl-3-yl)-7H-imidazo[4,5-c]pyridazine derivatives of formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4 and R5 are as defined in the description. The imidazopyridazine derivatives of the present invention modulate the activity of the GABAA receptor. They are useful in the treatment of a number of conditions, including pain.
INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL
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Page/Page column 64, (2014/07/08)
The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kirl.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and conditions associated with excessive salt and water retention.
INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL
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Page/Page column 69; 72, (2013/03/26)
The present invention provides compounds of Formula Ia and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and conditions associated with excessive salt and water retention.
SYNTHESIS OF INTERMEDIATES FOR PREPARING ANACETRAPIB AND DERIVATIVES THEREOF
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Page/Page column 37, (2013/07/05)
The present invention relates to the field of organic chemistry, more specifically to the synthesis of intermediate compounds which can be used in the synthesis of pharmaceutically active agents such as anacetrapib or derivatives thereof.
Synthesis of intermediates for preparing anacetrapib and derivates thereof
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Page/Page column 31, (2012/07/03)
The present invention relates to the field of organic chemistry, more specifically to the synthesis of intermediate compounds which can be used in the synthesis of pharmaceutically active agents such as anacetrapib or derivatives thereof.
Regioselective SNAr reactions of substituted difluorobenzene derivatives: practical synthesis of fluoroaryl ethers and substituted resorcinols
Ouellet, Stéphane G.,Bernardi, Anna,Angelaud, Remy,O'Shea, Paul D.
supporting information; experimental part, p. 3776 - 3779 (2009/10/11)
In this Letter, we describe a practical and highly selective method for the preparation of fluoroaryl ethers and differentially substituted resorcinol derivatives. This synthetic strategy relies on a selective SNAr of substituted difluorobenzen
