The crystal structure and absolute configuration of the two new title

The crystal structure and absolute configuration of the two new title nelfinavir analogs C24H35ClN4O5 (I) and C27H39ClN4O5 (II) have been determined. refining to 0.967?(6) and 0.033?(8). In both orientations the NO2 group is twisted out of the plane of the phenyl ring; the major orientation is twisted out of the plane less [O1-N1-C3-C2; τ = 10.9?(4)°] than the minor orientation [O1a slight rotation around the N4-C24 bond the site occupancies refining to 0.811?(17) and 0.189?(17). Similar to (I) both six-membered rings of the deca-hydro-iso-quinoline group in (II) adopt a chair conformation with a dihedral angle between the best-fit planes of the cyclo-hexyl and piperidine moieties of 116.3?(17)°. There is one weak intra-molecular hydrogen-bonding inter-action in (II) involving the parameter of 0.036?(19) and the Hooft parameter of 0.03?(2) indicate that the absolute configuration of (II) has been assigned correctly. Table 2 Hydrogen-bond geometry ( ) for (II) Supra-molecular features ? The extended structure of (I) is a two-dimensional sheet of hydrogen-bonded mol-ecules extending in the plane (Fig.?5 ? O-H?O and N-H?O inter-actions; the details of these inter-actions can be found in Table?1 ?. The two-dimensional layers stack in an pattern along the crystallographic axis (Fig.?5 ? and layers allows them to inter-digitate. Figure 5 A plot of the packing of (I) viewed (axis showing a hydrogen-bonded two-dimensional sheet overlaid with the unit cell and (axis showing how two layers stack together along the axis. Only the major component of disordered … The extended structure of (II) is a one-dimensional chain of hydrogen-bonded mol-ecules extending parallel to the crystallographic axis (Fig.?6 ? O-H?O inter-actions the details of these inter-actions can be found in Table?2 ?. The one-dimensional chains are separated from the cumbersome deca-hydro-iso-quinoline groups as well as the additional hydrogen-bonding inter-actions (Fig.?6 ? axis displaying a hydrogen-bonded one-dimensional string and (axis displaying the way the one-dimensional chains pack collectively overlaid with the machine cell. Just the major element of disordered … Data source study ? A search from the Cambridge Crystallographic Data source (CSD; Bridegroom & Allen 2014 ?) results just three crystal constructions using the the substitution in the N-atom placement from the deca-hydro-iso-quinoline group. One substance includes a 3-amino-2-hy-droxy-4-(phenyl-sulfan-yl)butyl group with this placement (CSD refcode QONJUY; Inaba HCl (2?ml). The response was dried as well as the solid URB754 was dissolved in ethyl acetate. The merchandise was washed double with water as soon as with brine dried out over sodium URB754 sulfate and focused by rotary evaporation. The merchandise was purified by silica flash column chromatography (gradient of 0-8% EtOAc URB754 in DCM) to yield racemic 4 as a colorless oil (yield 423?mg 75 yield). 1H NMR (500?MHz CDCl3): δ 7.33-7.28 (complex 5 5.63 (= 6?Hz 1 5.06 (+ H]+ calculated for C11H15ClNO3 244.074 observed 244.0741 For the synthesis of compound (I) compound 5 (104?mg 0.233 was dissolved in methanol (15?ml) with URB754 10% palladium on carbon (74?mg 0.07 The solution was degassed for 30?min before being placed under URB754 1 atm of hydrogen and stirred for 2?h at room temperature. The reaction was filtered through celite dried to a solid and taken up in tetra-hydro-furan (5?ml). 2-Chloro-4-nitro-benzoic acid (52?mg 0.256 3 hydro-chloride (49?mg 0.256 and hy-droxy-benzotriazole hydrate (42?mg 0.256 were added and the reaction was stirred at room CASP3 temperature overnight. The reaction was taken up in ethyl acetate washed once with sodium bicarbonate and once with brine and dried over sodium sulfate. The product was purified by silica flash-column chromatography (gradient of 0-3% MeOH in DCM) to yield (I) as a yellow solid (yield 77?mg 67 Crystals suitable for X-ray diffraction were obtained from the vapor diffusion of pentane into a solution of compound (I) in ethyl acetate at room temperature. 1H NMR (500?MHz CDCl3): δ 8.41 (= 4?Hz 1 8.24 (= 2?Hz 1 8.13 (= 8.5?Hz 1 5.6 (= 12?Hz 1 1.8 (complex 20 13 NMR (500?MHz CDCl3): δ 174.16 167.06 148.39 142 132.8 130.18 124.96 121.56 70.4 68.29 59.09 57.54 51.27 43.27 35.83 33.55 31.02 30.86 28.39 26.19 25.52 20.18 HRMS (+ H]+ calculated for C24H36ClN4O5 495.2374 observed 495.2376 Compound (II) was synthesized through the inter-mediate chloro-methyl hydroxyl 7 (Fig.?2 ?). Chloro-methyl ketone 6.

Comments are closed.

Post Navigation