New method for the methylation of amines

Borch, Richard F.; Hassid, Aviv

doi:10.1021/jo00975a049

Cited by 357 publications

(154 citation statements)

References 0 publications

Supporting

Mentioning

149

Contrasting

Unclassified

Order By: Relevance

“…33 Reaction times for ketones were far longer than for aldehydes, and zinc chloride was required to activate the ketone carbonyl group 34 to produce QJ035, QJ036, and QJ040. However, the reaction of pivaldehyde to produce 16 was very slow, even in the presence of zinc chloride.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Structure−Activity Relationship Studies of CD4 Down-Modulating Cyclotriazadisulfonamide (CADA) Analogues

et al. 2006

View full text Add to dashboard Cite

HIV attachment via the CD4 receptor is an important target for developing novel approaches to HIV chemotherapy. Cyclotriazadisulfonamide (CADA) inhibits HIV at submicromolar levels by specifically downmodulating cell-surface and intracellular CD4. An effective five-step synthesis of CADA in 30% overall yield is reported. This synthesis has also been modified to produce more than 50 analogues. Many tailgroup analogues have been made by removing the benzyl tail of CADA and replacing it with various alkyl, acyl, alkoxycarbonyl and aminocarbonyl substituents. A series of sidearm analogues, including two unsymmetrical compounds, have also been prepared by modifying the CADA synthesis, replacing the toluenesulfonyl sidearms with other sulfonyl groups. Testing 30 of these compounds in MT-4 cells shows a wide range of CD4 down-modulation potency, which correlates with ability to inhibit HIV-1. Threedimensional quantitative structure-activity relationship (3D-QSAR) models were constructed using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) approaches. The X-ray crystal structures of four compounds, including CADA, show the same major conformation of the central 12-membered ring. The solid-state structure of CADA was energy minimized and used to generate the remaining 29 structures, which were similarly minimized and aligned to produce the 3D-QSAR models. Both models indicate that steric bulk of the tail group, and, to a lesser extent, the sidearms mainly determine CD4 down-modulation potency in this series of compounds.

show abstract

Section: Resultsmentioning

confidence: 99%

Synthesis and Structure−Activity Relationship Studies of CD4 Down-Modulating Cyclotriazadisulfonamide (CADA) Analogues

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Reductice Al/g.lations at Acidic p H Having demonstrated that reductive alkylations carried out at alkaline p H give partially racemized Bzl-amino acids (Table 3), the use of cyanoborohydrides as reducing agent was examined; Tnese reagents of Borcht and Hassid (20) are stable down to p H 3, and effective at acidic pH. Indeed.…”

Section: Methylation By Successive Reducti~e Alkylationsmentioning

confidence: 99%

N-Methylamino acids in peptide synthesis. VII. Studies on the enantiomeric purity of N-methylamino acids prepared by various procedures

Cheung¹,

Benoiton²

1977

Can. J. Chem.

View full text Add to dashboard Cite

The enantiomeric purity of N-methylamino acids and their derivatives obtained by various procedures has been examined by analysis with an amino-acid analyzer of the diastereomeric lysyl dipeptides formed by coupling them with a lysyl derivative. N-Benzyloxycarbonyl, and N-tert-butyloxycarbonyl,N-methylamino acids obtained by methylation of the parent derivative using sodium hydride and methyl iodide, and N-methylamino acids obtained by methylation of the p-toluenesulfonylamino acid followed by treatment with sodium in liquid ammonia, are optically pure. Compounds obtained by other procedures which include reductive alkylations or the use of silver oxide – methyl iodide are generally not optically pure.

show abstract

“…In our hands this one pot method proved unsatisfactory for gram scale batches. We examined a stepwise approach and investigated a number of reagents for reductive methylation, including sulfuric acid mediated sodium borohydride / formaldehyde, 7 sodium cyanoborohydride formaldehyde in glacial acetic acid, 8 and direct treatment with dimethyl sulfate. 9 From this we determined that the combination of sodium cyanoborohydride / formaldehyde in methanol and 1 N hydrochloric acid was the most satisfactory method.…”

Section: Resultsmentioning

confidence: 99%

An improved synthesis of (S)-1-[[4-(dimethylamino)-3-methylphenyl]methyl]-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid ditrifluoroacetate dihydrate (PD123319)

Cundy¹,

Gurr²,

Knill³

et al. 2000

Arkivoc

View full text Add to dashboard Cite

show abstract

New method for the methylation of amines

Cited by 357 publications

References 0 publications

Synthesis and Structure−Activity Relationship Studies of CD4 Down-Modulating Cyclotriazadisulfonamide (CADA) Analogues

Synthesis and Structure−Activity Relationship Studies of CD4 Down-Modulating Cyclotriazadisulfonamide (CADA) Analogues

N-Methylamino acids in peptide synthesis. VII. Studies on the enantiomeric purity of N-methylamino acids prepared by various procedures

An improved synthesis of (S)-1-[[4-(dimethylamino)-3-methylphenyl]methyl]-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid ditrifluoroacetate dihydrate (PD123319)

Contact Info

Product

Resources

About