Source of materialAsolution of the cbz (cbz =benzyloxycarbon)protected (S)-N-((S)-1-phenylethyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide (1.0 g, 2.41 mmol) in THF (20 ml) was added to a suspension of activated 10 wt %Pd/C (0.5 g) in MeOH (20 ml). The mixture was connected to ahydrogen source at 1atmosphere and stirred at room temperature for 2hours. Completion of the reaction wasm onitored through TLC in hexane/ethyla cetate (50/50, R f =0.3). ThePd/C was filtered through acelite pad and washed with methanol (20 ml). The filtrate was evaporated under reduced pressure affording the crude amino ester, which was purified by columnc hromatography using ethyl acetate/hexane (50:50) as the eluent to yield the precusor (0.60 g, 89%) as awhite solid. M.p. =414-416 K. This compound was then dissolved in acetone and by slow evaporation, crystals suitable for x-ray diffraction were obtained. Experimental detailsAll hydrogen atomswere positioned geometrically with C-H distances ranging from 0.95 Åto1.00 Åand refined as riding on their parent atoms, with U iso (H) =1.2 -1.5 U eq (C). Crystals were very fragile and readily crumble when cut, so needles with length beinglargerthanthe x-raybeam size were used. The structure containssolvent accessible voidsof180.0 Å 3 andtwo residualswith largeelectrondensities of 1.53 and1.26e/Å -3 were observed. Attempts to model the solvent molecule failed despite data having been collectedtwice on twodifferent crystals. The solvent molecule waslocated on thefourfoldscrew axis whichrunning along [001]d irection and was severely disordered. Therefore the solvent was omitted from the final structure model. With unmerged reflections the Flack xp arameter equals to -0.7836 with esd 2.5357. So the final structure was refined with averaging Friedel pairs and the Rfactor is 0.05. Structure Contains Solvent Accessible VOIDS of 178 A 3 .SQUEEZE estimated atotal count of 40 electrons per unit cell contributed by the disordered solvents, which could not be modelled as discrete atomic sites. DiscussionAs part of our ongoing study into novel tetrahydroisquinoline (TIQ)based catalysts, the precusor to the title compound was synthesised [1][2][3]. In attempt to grow as ingle crystal of this compound, arange of different solvents were used by the method of slow evaporation. To ours urprise, the titlec ompound had recrystallised when acetone was used as the solvent. From literature tetrahydroindole based compounds undergo asimilar cyclisation in the presence of acetone [4]. These compounds are of interest due to its biological activity for its dual-acting ability to reverseresistanceand anti-cancer activity [5]. It is the first report of this tetrahydroisquinoline class with cyclisation between the secondary amine in the 6-membered ringa nd the amide nitrogen. Theabsolute stereochemistry of the crystal was confirmed to be S,S at C9 andC11 positions, respectively by proton NMRspectroscopy in keepingwiththe chiral starting aminoacidand amine. From theplain formed by theatoms C8-C7-C2-C1-N1-C9the di...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.