Solid phase reductive alkylation of secondary amines

Khan, Nawaz; Arumugam, Vijayalakshmi; Balasubramanian, Shankar

doi:10.1016/0040-4039(96)00945-8

Cited by 47 publications

(20 citation statements)

References 19 publications

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“…In order to chain extend the resin bound polyamine two methods of reductive amination were investigated. The most frequently used method uses the reducing agent NaBH 3 CN in trimethyl orthoformate (Look et al 1995) and, in an alternative method, reduction is performed using a borane± pyridine complex in THF under argon (Khan et al 1996, Bilodeau & Cunningham 1998. In our study, the best results for condensation of 8 to 3 were obtained with the borane±pyridine complex.…”

Section: Resultsmentioning

confidence: 71%

Solid-phase Organic Synthesis of Unnatural Polyamine Analogues Bearing a Dansyl or Acridine Moiety

Carrington¹,

Renault²,

Tomasi³

et al. 1999

Pharmacy and Pharmacology Communications

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The synthesis of unnatural polyamines and polyamine conjugates from a protected triamine anchored to Wang resin is described. The use of solid‐phase organic synthesis for such hydrophilic compounds is of interest because it removes the need for often awkward chromatographic purification of intermediates and is easily applied to the synthesis of compound libraries. Chain elongation was achieved by reductive amination and the resulting resin bound tetraamine was functionalized with dansyl and acridine moieties. The conjugates were cleaved from the resin and these studies should lead to the rapid synthesis of libraries for biological evaluation.

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Section: Resultsmentioning

confidence: 71%

Solid-phase Organic Synthesis of Unnatural Polyamine Analogues Bearing a Dansyl or Acridine Moiety

Carrington¹,

Renault²,

Tomasi³

et al. 1999

Pharmacy and Pharmacology Communications

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“…[25][26][27][28][29] In the case of secondary amines, due to the relative instability of the iminium ion intermediate, the classical method (aldehyde in the presence of a reducing agent such as NaBH 4 or NaCNBH 3 ) provides low yields. We employed the borane-pyridine complex (BAP) as a method for the synthesis of tertiary amines via reductive amination of 11d (Scheme 3, Table III), 30 but despite the good purity of the resulting final products, the reaction time (4 d) proved to be inconvenient for the efficient synthesis of other analogs in this series. Using TMOF as solvent and NaCNBH 3 as reducing agent, 31 we were able to perform the reductive amination of 11g (Scheme 4, Table IV).…”

Section: Resultsmentioning

confidence: 99%

Synthesis and biological evaluation of a targeted library of protein phosphatase inhibitors

Wipf

Aslan

Luci

et al. 2000

Biotechnol. Bioeng.

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Phosphorylation of serine, threonine, and tyrosine controls fundamental mammalian cell events and is achieved by kinases which, in turn, are in dynamic relationship with phosphatases. Few selective inhibitors of protein tyrosine and dual specificity phosphatases are readily available. Based on SAR studies of naturally occurring phosphatase inhibitors and following up on previously published research, we have designed a new pharmacophore model V and synthesized a new library of functional analogues of V. All synthetic steps were carried out and optimized employing combinatorial chemistry methods on Wang resin. All compounds were tested in vitro for their ability to inhibit recombinant human protein tyrosine (PTP1B) and dual‐specificity (Cdc25B2 and VHR) phosphatases. Three of the approximately 70 compounds in our library inhibited Cdc25B2 by 50% at 375–490 μM. No compounds inhibited PTP1B, and only one blocked VHR. Cell‐culture studies revealed no toxicity to human breast cancer cells with two of the phosphatase inhibitors. © 2000 John Wiley & Sons, Inc. Biotechnol Bioeng (Comb Chem) 71:58–70, 2000.

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“…After the deprotection step, the resulting secondary amines were subjected to reductive alkylation with aldehydes 16 (Scheme 2). This was achieved in situ using BAP, [26] resulting in clean reactions and high yields of products. Other reducing reagents examined, including NaBH 3 CN, NaBH(OAc) 3 , and Ti(OiPr) 4 , were found to be less effective.…”

Section: Synthesis Of Compounds 8 By Reductive Alkylation Of the Secomentioning

confidence: 99%

An Expeditious Library Synthesis of N‐Monoalkylated Aminopiperidines and ‐pyrrolidines

Ayesa¹,

Argyropoulos²,

Maltseva³

et al. 2004

Eur J Org Chem

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N‐Monosubstituted aminopiperidines and ‐pyrrolidines are important building blocks for the synthesis of small‐molecule compound libraries. We have developed a practical solid‐phase route to N‐monosubstituted aminopiperidines and ‐pyrrolidines utilizing a selective reductive alkylation of primary or secondary amines attached to a Merrifield or Wang resin. Purification is achieved by simple filtration after each reaction step. The synthetic route developed can be readily applied to an extensive pool of commercially available aromatic and aliphatic aldehydes for conversion into the corresponding N‐monoalkylated diamino templates. Solid‐phase NMR spectroscopy was used to monitor the reactions. The new pulse sequences described in this report have further extended the usefulness of this nondestructive analytical methodology. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

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Solid phase reductive alkylation of secondary amines

Cited by 47 publications

References 19 publications

Solid-phase Organic Synthesis of Unnatural Polyamine Analogues Bearing a Dansyl or Acridine Moiety

Solid-phase Organic Synthesis of Unnatural Polyamine Analogues Bearing a Dansyl or Acridine Moiety

Synthesis and biological evaluation of a targeted library of protein phosphatase inhibitors

An Expeditious Library Synthesis of N‐Monoalkylated Aminopiperidines and ‐pyrrolidines

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