Preparation of 1,5-Methano-2,3,4,5- tetrahydro-1<i>H</i>-3-benzazepine via Pd-Catalyzed Cyclization

Singer, Robert A.; McKinley, Jason D.; Barbe, and Guillaume; Farlow, Robin A.

doi:10.1021/ol049316s

Cited by 27 publications

(9 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, as both of these routes were found to be cumbersome upon scale-up due to the use of unstable and toxic reagents, a third strategy was developed utilising non-toxic commodity reagents (Scheme 44, pathway C) [110]. Therefore, 2-bromophenylacetonitrile ( 4.7 ) was subjected to a Michael addition with acrylate 4.8 followed by a Pd-catalysed cyclisation yielding indene 4.9 [111]. Under hydrogenation conditions this material furnished an amino-ester intermediate, which upon treatment with base produces lactam 4.10 .…”

Section: Reviewmentioning

confidence: 99%

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

Baumann¹,

Baxendale²

2013

Beilstein J. Org. Chem.

723

336

View full text Add to dashboard Cite

This review which is the second in this series summarises the most common synthetic routes as applied to the preparation of many modern pharmaceutical compounds categorised as containing a six-membered heterocyclic ring. The reported examples are based on the top retailing drug molecules combining synthetic information from both scientific journals and the wider patent literature. It is hoped that this compilation, in combination with the previously published review on five-membered rings, will form a comprehensive foundation and reference source for individuals interested in medicinal, synthetic and preparative chemistry. 2265

show abstract

Section: Reviewmentioning

confidence: 99%

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

Baumann¹,

Baxendale²

2013

Beilstein J. Org. Chem.

723

336

View full text Add to dashboard Cite

show abstract

“…The C–H arylation of 13 with 4-iodo- o -xylene was conducted on scales ranging from 77 mg to 2.5 g of substrate, with nearly identical yields of 14e (43% and 38% isolated yield, respectively). Based on the established synthesis of varenicline, an independent synthesis of these analogues by more traditional methods would require parallel multistep sequences 30 . In a similar fashion, our method proved effective for the late-stage C–H functionalization of the natural product cytisine ( 15 , a nicotine addiction treatment), converting 16 to 17 in 25% yield.…”

mentioning

confidence: 99%

Palladium-catalysed transannular C–H functionalization of alicyclic amines

Topczewski

Cabrera

Saper

et al. 2016

Nature

301

157

View full text Add to dashboard Cite

The discovery of pharmaceutical candidates is a resource-intensive enterprise that frequently requires the parallel synthesis of hundreds or even thousands of molecules. Carbon-hydrogen bonds are present in almost all pharmaceutical agents. As such, the development of selective, rapid, and efficient methods for converting carbon-hydrogen bonds into new chemical entities has the potential to dramatically streamline pharmaceutical development1,2,3,4. Saturated nitrogen-containing heterocycles (alicyclic amines) feature prominently in pharmaceuticals, including treatments for depression (paroxetine, amitifadine), diabetes (gliclazide), leukemia (alvocidib), schizophrenia (risperidone, belaperidone), and nicotine addiction (cytisine and varenicline)5. However, existing methods for the C–H functionalization of saturated nitrogen heterocycles, particularly at sites remote to nitrogen, remain extremely limited 6,7. Here we report a new approach to selectively manipulate the carbon–hydrogen bonds of alicyclic amines at sites remote to nitrogen. Our reaction leverages the boat conformation of the substrates to achieve the palladium-catalyzed amine-directed conversion of C–H bonds to C–C bonds on various alicyclic amine scaffolds. This approach is applied to the synthesis of novel derivatives of several bioactive molecules, including the top-selling smoking cessation drug varenicline (Chantix®). We anticipate that this method should prove broadly useful in medicinal chemistry.

show abstract

“…This prompted the search for an alternative strategy, not based on a DA reaction, which ultimately proved to be compatible with commercial‐scale requirements 113. 118 This example illustrates the typical difficulties of scaling up a DA reaction (especially when using cyclopentadiene monomer as a reagent) because of the heat of formation of the product and polymerization of the starting material. In this example, even though clinical batches were prepared by using this [4+2] cycloaddition pathway, a more competitive route was eventually found for industrial manufacturing.…”

Section: Active Pharmaceutical Ingredientsmentioning

confidence: 92%

Determination of Sudan IV in hot chilli powder with luminol/dissolved oxygen chemiluminescence system

2009

View full text Add to dashboard Cite

The proposed method was successfully applied to the determination of Sudan IV in contaminated hot chilli powder, with recoveries ranging from 89.3 to 108.4%. The possible mechanism of enhancement of the luminol/dissolved oxygen CL reaction by Sudan IV can be attributed to the acceleration of electron transfer. Compared with other procedures, the proposed CL method offers the highest sensitivity and the least reagent consumption for the determination of Sudan IV.

show abstract

Preparation of 1,5-Methano-2,3,4,5- tetrahydro-1H-3-benzazepine via Pd-Catalyzed Cyclization

Cited by 27 publications

References 4 publications

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

Palladium-catalysed transannular C–H functionalization of alicyclic amines

Determination of Sudan IV in hot chilli powder with luminol/dissolved oxygen chemiluminescence system

Contact Info

Product

Resources

About