Synthesis of (2R)-1-(4-Chloro-2-pyridyl)-2-(2-pyridyl)ethylamine: A Selective Oxime Reduction and Crystallization-Induced Asymmetric Transformation

Negi, Shigeto; Matsukura, Masayuki; Mizuno, Megumi; Miyake, Kazutoshi; Minami, Norio

doi:10.1055/s-1996-4325

Cited by 45 publications

(32 citation statements)

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“…Condensation of ketone 1a with hydroxylamine hydrochloride generated the oxime and subsequent reduction with zinc dust and TFA, according to the procedure of Negi, provided amine 1b. 29 Amide coupling of amine 1b with Boc-tranexamic acid gave 1c. The enantiomers of 1c were separated by chiral preparatory HPLC to give (S)-1c.…”

Section: Chemistrymentioning

confidence: 99%

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Orally bioavailable pyridine and pyrimidine-based Factor XIa inhibitors: Discovery of the methyl N-phenyl carbamate P2 prime group

Corte

Fang

Pinto

et al. 2016

Bioorganic & Medicinal Chemistry

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Pyridine-based Factor XIa (FXIa) inhibitor (S)-2 was optimized by modifying the P2 prime, P1, and scaffold regions. This work resulted in the discovery of the methyl N-phenyl carbamate P2 prime group which maintained FXIa activity, reduced the number of H-bond donors, and improved the physicochemical properties compared to the amino indazole P2 prime moiety. Compound (S)-17 was identified as a potent and selective FXIa inhibitor that was orally bioavailable. Replacement of the basic cyclohexyl methyl amine P1 in (S)-17 with the neutral p-chlorophenyltetrazole P1 resulted in the discovery of (S)-24 which showed a significant improvement in oral bioavailability compared to the previously reported imidazole (S)-23. Additional improvements in FXIa binding affinity, while maintaining oral bioavailability, was achieved by replacing the pyridine scaffold with either a regioisomeric pyridine or pyrimidine ring system.

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Section: Chemistrymentioning

confidence: 99%

“…Compound 1b was prepared following a modified procedure of Negi. 29 To a clear, yellow solution of 1a (3.96 g, 17.1 mmol) in MeOH (34 mL) was added hydroxylamine hydrochloride (3.56 g, 51.3 mmol). The resulting suspension was stirred at rt.…”

Section: -(4-chloropyridin-2-yl)-2-phenylethan-1-amine (1b)mentioning

confidence: 99%

Orally bioavailable pyridine and pyrimidine-based Factor XIa inhibitors: Discovery of the methyl N-phenyl carbamate P2 prime group

Corte

Fang

Pinto

et al. 2016

Bioorganic & Medicinal Chemistry

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“…30 Treatment with hydroxylamine hydrochloride yielded the oxime 17. Reduction by Zn in triuoroacetic acid 31 followed by treatment with an aryl-sulfonylchloride derivative yielded the sulfonamide-pyridines 18 and 19, respectively.…”

Section: 27mentioning

confidence: 99%

Human carbonic anhydrase II as host protein for the creation of artificial metalloenzymes: the asymmetric transfer hydrogenation of imines

et al. 2013

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In the presence of human carbonic anhydrase II, aryl-sulfonamide-bearing IrCp* pianostool complexes catalyze the asymmetric transfer hydrogenation of imines. Critical cofactor-protein interactions revealed by the X-ray structure of [(h 5 -Cp*)Ir(pico 4)Cl] 9 3 WT hCA II were genetically optimized to improve the catalytic performance of the artificial metalloenzyme (68% ee, k cat /K M 6.11 Â 10 À3 min À1 mM À1).

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“…They play an important role as synthetic intermediates en route to nitriles [55], nitro compounds [56], nitrones [57], amines [58], and isoxazolines [59], and also as -activating group in synthetic organic chemistry [60]. Oxidative deoximation methods which have been developed in recent years [61] consist of toxic metals such as Ce(IV), Pb (IV) and Cr(VI).…”

Section: Deprotection Of Oximes To Carbo-nyl Groupsmentioning

confidence: 99%

Heteropoly acids, their salts and polyoxometalates as heterogenous, efficient and eco-friendly catalysts in organic reactions: Some recent advances

Firouzabadi

Jafari

2005

JICS

108

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Synthesis of (2R)-1-(4-Chloro-2-pyridyl)-2-(2-pyridyl)ethylamine: A Selective Oxime Reduction and Crystallization-Induced Asymmetric Transformation

Cited by 45 publications

References 0 publications

Orally bioavailable pyridine and pyrimidine-based Factor XIa inhibitors: Discovery of the methyl N-phenyl carbamate P2 prime group

Orally bioavailable pyridine and pyrimidine-based Factor XIa inhibitors: Discovery of the methyl N-phenyl carbamate P2 prime group

Human carbonic anhydrase II as host protein for the creation of artificial metalloenzymes: the asymmetric transfer hydrogenation of imines

Heteropoly acids, their salts and polyoxometalates as heterogenous, efficient and eco-friendly catalysts in organic reactions: Some recent advances

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