75659-06-2

Usage

Uses

(αR)-α-Methyl-N-(phenylmethyl)benzenepropanamine is an intermediate in the synthesis of (R,R)-Labetalol (L096500), a specific competitive antagonist at both α-and β-adrenergic receptor sites. (R,R)-Labetalol is used as an antihypertensive.

Upstream product

• 68164-04-5 N-benzyl-1-methyl-3-phenylpropylamine 
• 118620-50-1 Benzyl-[(S)-3-phenyl-1-((R)-toluene-4-sulfinylmethyl)-propyl]-amine 
• 4187-36-4 ((R)-1-Methyl-3-phenyl-propyl)-[1-phenyl-meth-(E)-ylidene]-amine 
• 100-46-9 benzylamine 
• 2344-70-9 1-phenyl-3-butanol 
• 2550-26-7 4-Phenyl-2-butanone 
• 83167-23-1 Benzyl-[1-methyl-3-phenyl-prop-(E)-ylidene]-amine 
• 937-52-0 (R)-1-methyl-3-phenylpropylamine 
• 100-52-7 benzaldehyde 
• 88976-53-8 *,R^*)>-α-methyl-N-(1-phenylethyl)benzenepropanamide 
• 1220-80-0 (S)-4-methyl-2-(toluene-4-sulfonamido)pentanoic acid 
• 1188-21-2 N-Ac-Leu 
• 768-56-9 4-Phenylbut-1-ene 
• 93-58-3 benzoic acid methyl ester 

Downstream Products

• 81580-36-1 (R)-2-hydroxy-5-<acetyl>benzamide 
• 75615-53-1 5-<<<(R)-1-methyl-3-phenylpropyl>(phenylmethyl)amino>acetyl>-2-(phenylmethoxy)benzamide 
• 83167-32-2 (S,R)-labetalol 
• 75659-07-3 (R,R)-labetalol 
• 81602-13-3 *)>-2-hydroxy-5-<1-hydroxy-2-<(1-methyl-3-phenylpropyl)amino>ethyl>benzamide hydrochloride 
• 75659-08-4 (R,R)-Labetalol hydrochloride 
• 75615-55-3 *,R^*)>-5-<1-hydroxy-2-ethyl>-2-(phenylmethoxy)benzamide 
• 81580-37-2 *,S^*)>-5-<1-hydroxy-2-ethyl>-2-(phenylmethoxy)benzamide 

Relevant academic research and scientific papers

Resolution of racemic amines via lipase-catalyzed benzoylation: Chemoenzymatic synthesis of the pharmacologically active isomers of labetalol

Lipase-catalyzed benzoylation of amines was shown to be feasible, in some cases with high enantioselectivity, and the best results were obtained using immobilized lipase from Candida antarctica (Novozym 435) and methyl benzoate as acyl donor in the presence of molecular sieves. The procedure was optimized for the resolution of (±)-1-methyl-3-phenylpropylamine, a key intermediate in the synthesis of antihypertensive drug labetalol, and the enantiopure (R)-benzamide was then converted into the pharmacologically active isomers of the drug. In comparison with the reported synthesis of chiral isomers of labetalol, this chemoenzymatic route offers the advantage in the lack of any chiral stoichiometric auxiliary.

Asymmetric Intra- and Intermolecular Hydroamination Catalyzed by 3,3′-Bis(trisarylsilyl)- and 3,3′-Bis(arylalkylsilyl)-Substituted Binaphtholate Rare-Earth-Metal Complexes

The series of novel 3,3′-bis(trisarylsilyl)- and 3,3′-bis(arylalkylsilyl)-substituted binaphtholate rare-earth-metal complexes 2a-i (SiR3 = Si(o-biphenylene)Ph (a), SiCyPh2 (b), Si-t-BuPh2 (c), Si(i-Pr)3 (d), SiCy2Ph (e), Si(2-tolyl)Ph2 (f), Si(4-t-Bu-C6H4)3 (g), Si(4-MeO-C6H4)Ph2 (h), SiBnPh2 (i)) have been prepared via arene elimination from [Ln(o-C6H4CH2NMe2)3] (Ln = Y, Lu) and the corresponding 3,3′-bis(silyl)-substituted binaphthol. The complexes exhibit high catalytic activity in the hydroamination/cyclization of aminoalkenes, with activities exceeding 1000 h-1 for (R)-2f-Ln, (R)-2g-Ln, and (R)-2h-Ln in the cyclization of 2,2-diphenylpent-4-enylamine (3a) at 25 °C, while the rigid dibenzosilole-substituted complexes (R)-2a-Ln and the triisopropylsilyl-substituted complexes (R)-2d-Ln exhibited the lowest activity in the range of 150-270 h-1. Catalysts (R)-2b-Lu, (R)-2c-Lu, (R)-2f-Lu, and (R)-2i-Lu provide the highest selectivities for the majority of the substrates, while the yttrium congeners are usually less selective. The highest enantioselectivities of 96% ee were observed using (R)-2a-Lu and (R)-2c-Lu in the cyclization of (4E)-2,2,5-triphenylpent-4-enylamine (9). The reactions show apparently zero-order rate dependence on substrate concentration and first-order rate dependence on catalyst concentration, with some reactions exhibiting a slightly accelerated rate at high conversion due to a shift in the equilibrium between a less active, higher coordinate catalyst species in favor of a more active, lower coordinate species as a result of weaker binding of the hydroamination product in comparison to the aminoalkene substrate. The shift in equilibrium from the higher to the lower coordinate species is also entropically favored at elevated temperatures, which results in an unusual increase in selectivity in the cyclization of 2,2-dimethylpent-4-enylamine (3d), presumably due to a higher selectivity of the lower coordinate catalyst species. All binaphtholate yttrium complexes, except (R)-2a-Y, are catalytically active in the intermolecular hydroamination of benzylamines with terminal alkenes. The highest selectivity of 66% ee was observed for the reaction of benzylamine with 4-phenyl-1-butene using (R)-2h-Y at 110 °C.

C1-symmetric rare-earth-metal aminodiolate complexes for intra- and intermolecular asymmetric hydroamination of alkenes

A series of novel C1-symmetric aminodiolate rare-earth-metal complexes have been prepared via arene elimination from [Ln(o-C 6H4CH2NMe2)3] (Ln = Y, Lu) and the corresponding aminodiol proligand. The NOBIN-derived aminodiolate ligands feature sterically demanding triphenylsilyl and methyldiphenylsilyl ortho substituents on the naphtholate moiety and substituents of varying steric demand ranging from tert-butyl to tris(3,5-xylyl)silyl on the phenolate moiety. Complexes with a triphenylsilyl substituent on the naphtholate moiety displayed good catalytic activity in the hydroamination/cyclization of aminoalkenes, while complexes with a methyldiphenylsilyl substituent exhibited somewhat lower reactivity. The highest enantioselectivities for five- and six-membered-ring formation were observed utilizing complex 9c-Lu (R1 = Ph, R 2 = Me, R3 = SiPh3) in the cyclization of (2,2-diphenylpent-4-enyl)amine (92% ee, Nt = 200 h-1 at 25 C) and (2,2-diphenylhex-5-enyl)amine (73% ee, Nt = 20 h-1 at 25 C). The complexes can be applied in asymmetric intermolecular hydroaminations of 1-heptene and 4-phenyl-1-butene with benzylamine with enantioselectivities of up to 40% ee using complex 9b-Y (R1 = Ph, R2 = Me, R3 = SiPh2Me). Here the higher catalytic activities are achieved with catalysts having a methyldiphenylsilyl substituent on the naphtholate moiety. Lanthanum aminodiolate catalysts generated in situ from [La{CH(C6H5)NMe2} 3] did not exhibit improved catalytic activity in the intermolecular hydroamination in comparison to the corresponding yttrium and lutetium catalysts. The overall catalytic activities of the aminodiolate complexes are somewhat diminished in comparison to previously studied binaphtholate complexes due to the presence of the additional amine donor site in the ligand framework.

Asymmetric intermolecular hydroamination of unactivated alkenes with simple amines

A hard nut to crack: The asymmetric intermolecular Markovnikov addition of simple amines to unactivated alkenes can be achieved utilizing binaphtholate rare-earth-metal catalysts with up to 61% ee and 73% de in the case where R 2 contains a stereogenic center.

Towards a practical br?nsted acid catalyzed and hantzsch ester mediated asymmetric reductive amination of ketones with benzylamine

We report the use of benzylamine as the amine component in Hantzsch ester mediated and chiral Br?nsted acid catalyzed enantioselective reductive aminations of ketones. The method is noteworthy because the benzyl group is easily removable, and amine product purification is achieved through Hantzsch ester oxidation product removal via basic hydrolysis.

1,1′-Binaphthyl-2,2′-diyl phosphoroselenoyl chloride as a chiral molecular tool for the preparation of enantiomerically pure alcohols and amines

Enantiomerically pure phosphoroselenoyl chloride bearing a binaphthyl group was synthesized. This phosphoroselenoyl chloride was used to discriminate and resolve simple secondary alcohols. Stereospecific conversions of diastereomerically pure phosphoroselenoic acid esters, obtained by reaction of the chloride with simple secondary alcohols, to enantiomerically pure alcohols and amines were also achieved. Copyright

CONJUGATE ADDITION OF AMINES TO CHIRAL (E) AND (Z) VINYL SULFOXIDES, AN ENANTIOCONVERGENT AND KINETIC PROCESS

The kinetically controlled conjugate addition of benzylamine to isomeric (E) or (Z) chiral vinyl sulfoxides affords the same major diastereomeric adduct.

TREATMENT OF HYPERTENSION

Compositions containing (-)-5-{(R)-1-Hydroxy-2 (R)-1-methyl-3-phenylpropyl)amino!ethyl}salicylamide exhibit potent vasodilating β-adrenergic blocking properties and are useful for the treatment of hypertension.

Synthesis and Comparison of Some Cardiovascular Properties of the Stereoisomers of Labetalol

A useful method for the separation of labetalol into its two racemic diastereomers, as well as a stereoselective synthesis of its four stereoisomers, is described.The absolute stereochemistry of each isomer was determined by analysis of the CD spectra and confirmed by X-ray analysis.The α- and β1-adrenergic blocking properties, as well as the relative antihypertensive activities, have been measured in rats.The R,R isomer, 2a (SCH 19927), possesses virtually all of the β1-blocking activity elicited by labetalol and displays little α-blocking activity.In contrast, the S,R isomer, 3a, has most of the α-blocking activity.Of the four isomers, only 2a has antihypertensive potency comparable to that of labetalol.These findings, coupled with published data showing that labetalol possesses β-adrenergic mediated peripheral vasodilating activity deriving essentially from its R,R isomer, lead to the following conclusion: The antihypertensive activity of labetalol can be ascribed to at least three identified complementary mechanisms, β-adrenergic blockade, β-adrenergic mediated vasodilatation, and α-adrenergic blockade, whereas the antihypertensive activity of 2a derives from the first two mechanisms only.