Synthesis and antibacterial activities of N-substituted-glycinyl 1H-1,2,3-triazolyl oxazolidinones

Article abstract of DOI:10.1016/j.ejmech.2013.05.041

A series of 1H-1,2,3-triazolyl piperazino oxazolidinone analogs with optionally varied glycinyl substitutions were synthesized and their antibacterial activity assessed against a panel of susceptible and resistant Gram-positive and selected Gram-negative

Full text of DOI:10.1016/j.ejmech.2013.05.041

Accepted Manuscript
Synthesis and antibacterial activities of N-substituted-glycinyl 1H-1,2,3-triazolyl
oxazolidinones
Oludotun A. Phillips, Edet E. Udo, Mohammed E. Abdel-Hamid, Reny Varghese
PII:
S0223-5234(13)00359-0
10.1016/j.ejmech.2013.05.041
EJMECH 6219
DOI:
Reference:
To appear in: European Journal of Medicinal Chemistry
Received Date: 2 March 2013
Revised Date: 28 May 2013
Accepted Date: 29 May 2013
Please cite this article as: O.A. Phillips, E.E. Udo, M.E. Abdel-Hamid, R. Varghese, Synthesis and
antibacterial activities of N-substituted-glycinyl 1H-1,2,3-triazolyl oxazolidinones, European Journal of
Medicinal Chemistry (2013), doi: 10.1016/j.ejmech.2013.05.041.
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ACCEPTED MANUSCRIPT
Graphic Abstract
Synthesis and antibacterial activities of N-substitutedglycinyl 1H-1,2,3-triazolyl oxazolidinones
Oludotun A. Phillips, Edet E. Udo, Mohammed E. Abdel-Hamid and Reny Varghese
A series of N-substituedglycinyl-1H-1,2,3-triazolyl oxazolidinone derivatives were synthesized and
evaluated for antibacterial activities against Gram-positive and Gram-negative susceptible and
resistant clinical isolates.

ACCEPTED MANUSCRIPT
Synthesis and antibacterial activities of N-substituted-glycinyl 1H-1,2,3-triazolyl
oxazolidinones
a †
b
a
Oludotun A. Phillips , Edet E. Udo , Mohammed E. Abdel-Hamid ,
a
Reny Varghese
a
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kuwait University,
b
P. O. Box 24923, Safat 13110, Kuwait, Department of Microbiology, Faculty of
Medicine, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait.
†
Author to whom correspondence should be addressed; Tel: +(965) 2463-6070
Fax: +(965) 2463-6898; e-mail: dphillips@hsc.edu.kw
E-mail addresses: edet@hsc.edu.kw; abdel-hamid@hsc.edu.kw; renynv@hsc.edu.kw
Running Title Head
Antibacterial Activity of Glycinyl Triazolyl Oxazolidinones.
Key Words: Antibacterial activity, Gram-positive bacteria, Linezolid, Substituted-
glycinyl oxazolidinone, Triazolyl-oxazolidinone.
1

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Abstract
A series of 1H-1,2,3-triazolyl piperazino oxazolidinone analogs with optionally varied
glycinyl substitutions were synthesized and their antibacterial activity assessed
against a panel of susceptible and resistant Gram-positive and selected Gram-negative
bacteria including clinical isolates. The N-aroyl- and N-heteroaroyl-glycinyl (MIC:
0
.06-4 µg /ml) derivatives were more potent than the N-acylglycinyl (2-8 µg/ml)
derivatives against all Gram-positive bacteria tested. Nitro substitution on aryl and
heteroaryl rings significantly enhanced activity against Gram-positive bacteria, as
noted with the 3,5-dinitrobenzoyl (6m and 6n) and 5-nitro-2-furoyl (6u and 6v)
derivatives with MIC ranges of and 0.25-0.5 and 0.06-0.5 µg /ml, respectively. These
nitro analogs also showed more potent extended activity against M. catarrhalis, with
MICs ranges of 0.25-1 µg /ml, compared to linezolid (MIC: 8 µg /ml). Hence, the
presence of the N-aroyl and / or N-heteroaroyl glycinyl structural motifs as spacer
group could significantly enhance the antibacterial activities of 1H-1,2,3-triazolyl
oxazolidinone class of compounds.
2

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1
.0 Introduction
The increasing frequency of bacterial infections with antibiotic-resistant strains,
particularly the Gram-positive organisms both in the community and hospital settings
world-wide continue to serve as impetus for search for new, more effective and safer
antibacterial agents. Oxazolidinones, exemplified by Linezolid (Lzd, 1; Fig. 1),
represent a relatively new class of antibacterial agents with potent activity against
Gram-positive bacteria pathogens, including multidrug-resistant strains namely,
methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant
Streptococcus pneumoniae (PRSP) and vancomycin-resistant enteroccoci (VRE) [1].
These Gram-positive bacteria are frequent causes of serious infection among patients
in the hospital and community [2]. The emergence of bacterial resistance to known
antibacterial agents continue to be a major health problem world-wide and thus
provides an impetus for the efforts directed towards the discovery of novel, more
efficacious and safer antibacterial agents [2-3].
Oxazolidinone class of compounds have been extensively studied and shown to
inhibit bacterial protein biosynthesis by binding to sites on the bacterial ribosomes,
thus preventing formation of the functional 70S initiation complex [4-5]. However,
the most recent studies by Duffy et.al. [6] divulged that linezolid binds to the A-site of
the 50S subunit, thus preventing binding of the aminoacyl-tRNA to this site.
Extensive structural modifications around the phenyl-oxazolidinone moiety have been
performed with the aim of identifying novel derivatives with extended antibacterial
spectrum and decreased side-effects [7-8]. Other studies have shown that
incorporation of diverse substituents such as the 3-aryl or heteroaryl ring at the 4-
position of the 3-phenyloxazolidinone moiety significantly enhanced antibacterial
potency, even when the C-5 position contains an acetamidomethyl or hydroxymethyl
3

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group (4a-b; Fig 1) [8]. Furthermore, these substituent groups have been
demonstrated to extend antibacterial potency against linezolid-resistant MRSA
ribosomal mutants, with MIC ranges of 0.5 to 1 µg/ml in comparison to Lzd with
MIC ranges of 2-32 µg/ml. We have been interested in the triazolyl-oxazolidinone
derivatives and have reported the potent activities for the several triazolyl
oxazolidinone derivatives bearing the morpholino group, general structure 2 (PH027,
PH084; Fig 1) and N-substitutedpiperazino (3, Fig 1) moieties at the position 4 of the
phenyl ring [9-11]. In addition, structure-activity relationships studies from others [8]
have yielded other derivatives (4a-b, Fig 1) having the biheteroaryl or heteroaryl-
substitutedphenyl groups at the position 4 of the phenyl-oxazolidinone. These
derivatives showed improved antibacterial activities coupled with significantly
improved binding at the bacterial ribosomal site. The introduction of “spacer groups”
containing hydrogen bond donor and / or acceptor groups on the terminal substituent
moiety at the C-4 position of the phenyl-oxazolidinone pharmacophore have been
implicated in the potent antibacterial activities due to enhanced interactions at the
bacterial 50S ribosomal binding sites [8, 12-14]. Recently, introduction of substituted-
glycinyl moieties as spacer on the 4N-piperazinyl position of eperezolid yielded
compounds with the general structure 5 (Fig 1). Computational structural analysis
studies of the binding of these compounds at the bacterial ribosomal active site
revealed that a H-bond acceptor and / or donor group is an essential structural motif
that would fit a potential pocket identified at the bacterial ribosomal receptor site [12].
Based on these observations we synthesized the substituted-glycinyl derivatives of
general structure (6a-x, Fig 1) containing varied H-bond donor and acceptor groups at
the terminal N-glycinyl position. We herein report the synthesis of a series of new 5-
(4-methyl-1H-1,2,3-triazole)methyl and 5-(4-methyl-1H-1,2,3-triazole)
4

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oxazolidinones, which are expected to exhibit enhanced binding at the active site and
improve antibacterial activity against susceptible and multidrug-resistant Gram-
positive bacteria.
Insert: Figure 1.
2
.0 Chemistry
The synthesis of the final piperazine oxazolidinone derivatives 16a-x is illustrated in
Scheme 1. Starting from the readily available piperazine 7 and 3,4-difluoroaniline 8
the intermediate trifluoroacetic acid salt derivatives 13 and 14 were obtained in
quantitative yields, respectively, in multi-step reactions according to previously
published procedures [11, 15-16]. Further chemical transformation of 13 and 14 were
by reacting with N-tert-butoxycarbonylglycine activated with DCC and 1-HOBT as
coupling reagents gave the boc-protected glycinyl-derivatives 6a-b in very good
yields. Deprotection of the boc-protected glycinyl-oxazolidinones 6a-b with
o
trifluoroacetic acid in CH
2
Cl
2
at 0 C to room temperature gave the key-intermediate
N-glycinyl-oxazolidinones derivatives 15 and 16 as the trifluoroacetic acid salts in
quantitative yields. To obtain the target compounds (6c-x), further derivatization of
the intermediate oxazolidinone derivatives 15 and 16 were performed by subsequent
reactions with appropriate acid chlorides or anhydrides and arylsulfonyl chlorides in
2 2 3
CH Cl /CH CN and triethylamine in moderate to excellent yields.
Insert: Scheme 1.
5

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3
.0 Results and Discussion
The synthesized N-substitutedglycinyl oxazolidinones 6a-x were evaluated for in
vitro antibacterial activity against selected antibiotic-susceptible and -resistant
clinical isolates, and standard strains of Gram-positive and Gram-negative bacteria.
Gram-positive strains tested included MRSA, methicillin-susceptible S. aureus
(MSSA), methicillin-resistant coagulase-negative staphylococci (MR-CNS),
methicillin-sensitive coagulase-negative staphylococci (MS-CNS), PRSP, VRE, and
vancomycin-sensitive (VSE) enterococci. The selected Gram-negative organisms
were limited to E. coli ATCC 25922, H. influenzae ATCC 49247 and M. catarrhalis
ATCC 8176 and clinical strains of M. catarrhalis. The standard agar dilution method
according to the National Committee for Clinical Laboratory [17] was employed to
determine the minimum inhibitory concentration (MIC, µg/ml) values in vitro. The
results of in vitro antibacterial activity against several bacterial strains are
summarized in Table 1. Overall, most of the compounds showed potent to moderate
(MIC range < 0.25 to 8 µg/ml) antibacterial activity against staphylococcal and
enterococcal strains with the exception of the tetrahydrofuran-2-carbonyl (6j) and
thiophene-2-sulfonamide (6x) derivatives with MIC ranges of ≥ 8-32 µg/ml. Both of
these compounds contain a methyl group at the C-5 position of the triazole ring. All
the tested compounds exhibited potent antibacterial activity against S. pneumoniae
(MIC ranges of < 0.25 - 4 µg/ml), with the exception of the tert-butoxycarbonyl
derivative 6b. The substitution of an aroyl and / or heteroaroyl moieties on the N-
glycine enhanced antibacterial activity against Gram-positive bacterial strains. While
the nitro substitution on the furan ring resulted in compounds 6u-v, which are found
to be 4-8 -fold more active than linezolid and other reference compounds evaluated in
this study.
6

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Insert: Table 1.
From the antibacterial evaluation results (Table 1), none of the compounds showed
activity against E. coli and only selected compounds, namely, the nicotinoyl (6o), 2-
furoyl (6t), and the 5-nitro-2-furoyl (6u-v) derivatives showed comparable activity to
linezolid (MIC = 8 µg/ml) against the H. influenzae reference strain ATCC49247 with
MIC value ranges of ≥ 2-8 µg/ml. A number of the benzoyl (6l) and heteroaroyl (6o-r
and 6t) derivatives exhibited antibacterial activity comparable to that of linezolid
(MIC = 8 µg/ml) against a standard strain of M. catarrhalis. While the 3,5-dinitro-
benzoyl (6m-n, MIC = 0.5 and 1 µg/ml) and 5-nitro-2-furoyl (6u-v, MIC = 1 and 0.5
µg/ml) derivatives were 8-10 -fold more active than linezolid (MIC = 8 µg/ml)
against the same strain. Based on this activity, a total of 10 compounds were selected
and further evaluated against M. catarrhalis clinical isolates (n=8). The results are
presented in Table 2. The superior antibacterial activities of the 3,5-dinitrobenzoyl
(6m-n) and 5-nitro-2-furoyl (6u-v) derivatives compared to linezolid were obvious in
all the strains.
These nitroaroyl and nitroheteroaroyl substituted compounds demonstrate more potent
antibacterial activities against Gram-positive bacterial and M. catarrhalis strains
compared to linezolid and the eperezolid analogs with glycinyl substitutions of
general structure 5 reported by Wang et al. [13]. Although Wang et al.[13] did not
report any activity against M. catarrhalis strains they suggested that N-acyl-, N-aroyl-
or N-heteroaroyl-glycinyl structural motif plays a key role in enhancing antibacterial
activity. In addition, a recently published study from our laboratory have shown that
incorporation of the 5-nitro-2-furoyl and dinitrobenzoyl groups selectively enhanced
7

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antibacterial activity of some piperazinyl triazolyl-oxazolidinones against Gram-
positive bacterial strains [16]. However, the results from our presence study showed
that the combined presence of N-(3,5-dinitrobenzoyl)- or N-(5-nitro-2-furoyl)-
glycinyl structural motif and a 5-triazolyl or 5-(4-methyltriazolyl) groups resulted in
more potent triazolyl-oxazolidinone analogs with extended antibacterial activity
against M. catarrhalis strains.
Insert: Table 2.
In order to assess the extent of plasma binding and / or plasma instability, test
compounds were evaluated against S. aureus ATTC 25923 in Mueller-Hinton (MH)
broth supplemented with 50% human plasma, and the results are presented in Table 3.
In general, only a few of the compounds showed a fourfold or higher MIC values in
the presence of 50% human plasma, which indicated potential significant plasma
protein binding. Of the most active derivatives in this series of compounds, the of N-
(3,5-dinitrobenzoyl)- glycinyl derivatives 6n-m exhibited 16 and 4-fold increases in
MIC in the presence of 50% plasma. On the other hand, the N-(5-nitro-2-furoyl)-
glycinyl derivatives retained their activity in 50% human plasma. Overall, no direct
correlations could be established between antibacterial activity or plasma protein
binding and the calculated log of partition coefficient (C log P) values.
Insert: Table 3.
8

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4
.0 Conclusions
The synthesis and antibacterial activities of a number of new 1H-1,2,3-triazolyl
piperazino oxazolidinone analogs bearing optionally substituted N-glycinyl groups
have been reported. These compounds showed moderate to strong antibacterial
activities against standard reference strains and clinical isolates of streptococci,
enterococci and staphylococci. While the nitrofuran-2-carbonyl analogs 6u-v, showed
antibacterial activity that is 4-8 -fold more active than linezolid and other reference
compounds used. Furthermore, the N-(3,5-dinitrobenzoyl)- (6m-n) and N-(5-nitro-2-
furoyl)- (6u-v) derivatives were also 8-10 -fold more active than linezolid against the
fastidious Gram-negative bacteria M. catarrahlis strains. This study highlighted the
presence of the N-aroyl and / or N-heteroaroyl glycinyl structural motifs as potential
spacer group that could significantly enhance both the antibacterial activities of the
1
H-1,2,3-triazolyl oxazolidinone class of compounds and their affinity at the bacterial
ribosomal binding site.
5
.0 Experimental
5
.1 Characterization
Column chromatography was carried out with silica gel (Kieselgel 60, 70-230 mesh;
Aldrich) and TLC conducted on 0.25 mm pre-coated silica gel plates (60F , Merck).
254
Melting points were determined on a Stuart Scientific melting point apparatus (SMP1,
1
UK) and were uncorrected. H-NMR spectra were recorded on Bruker Avance II 600
13
NMR spectrometer. In addition, the C-NMR spectrum of representative compounds
6
k, 6q, 6u, 6v, 6w and 6x, were recorded on Bruker Avance II 600 NMR
1
3
13
spectrometer. The C-NMR experiments performed included C-NMR decoupled,
9

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1
3
13
C-DEPT-135 (Distortionless Enhancement by Polarization Transfer-139) and C-
APT (Attached Proton Test). Chemical shifts of protons are reported in parts per
million (ppm) downfield from tetramethylsilane (TMS) as an internal reference or
6
DMSO-d (δ=2.5; 39.7) as solvent. Mass spectra were recorded on a Thermo
Scientific DFS High Resolution Gas Chromatography / Mass Spectrometer (DFS GC-
MS) and Quattro LC (Micro Mass, UK) Mass Spectrometer. Infrared (IR) spectra
were recorded on JASCO FT-IR-6300 (JASCO, Japan) spectrometer. Elemental
analyses were performed on an Elementar Vario Micro Cube CHN Analyzer
apparatus (Elementar, Germany), and analyses indicated by the symbols of the
elements were within ± 0.4% of the theoretical values. Analyses were performed at
the Science Analytical Facilities (SAF), Faculty of Science, and Department of
Pharmaceutical Chemistry, Faculty of Pharmacy, Kuwait University, Kuwait. The
structures of the oxazolidinones were sketched and the Clog P values estimated using
PerkinElmer, ChemDraw Ultra 13.0 (CambridgeSoft, USA, 2012).
5
.2. Syntheses
5
.2.1. (R)-2-(4-(4-(5-((1H-1,2,3-Triazol-1-yl)methyl)-2-oxooxazolidin-3-yl)-2-
fluorophenyl) piperazin-1-yl)-2-oxoethanaminium 2,2,2-trifluoroacetate (15)
A solution of N-tert-butoxycarbonylglycine (1.52 g, 8.69 mmol) in anhydrous DCM
(
15 mL) under N
benzotriazole (1.47 g, 10.86 mmol) and the mixture stirred for 2 hrs at r.t. under N
The reaction mixture was filtered directly into a round bottom flask containing (R)-4-
4-(5-((1H-1,2,3-triazol-1-yl)methyl)-2-oxooxazolidin-3-yl)-2-fluorophenyl)
piperazin-1-ium 2,2,2-trifluoroacetate (13; 4.0 g, 8.69 mmol) and triethylamine (3.51
mL) in anhydrous CH CN (60 mL). The reaction mixture was stirred overnight at r.t.
2
was treated with DCC (2.24 gm, 10.86 mmol) and 1-hydroxy-
2
.
(
3
1
0

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under N
2
and concentrated under vacuum to give a gum, which was dissolved in ethyl
2 3 2 4
acetate (40 mL), washed with 10% Na CO , water, brine, dried (Na SO ) and
concentrated on rotovap to afford a white solid. Recrystallization (Ethyl acetate –
o
1
hexane) gave 6a as a solid (3.20 g, yield, 80%), mp- 150-152 C. H-NMR (DMSO-
d
1
6
, 600 MHz): δ 8.16 (s, 1H, NH), 7.76 (s, 1H, triazolyl H), 7.42 (dd, 1H, J=2.5 Hz,
4.7 Hz, phenyl H), 7.12 (dd, 1H J=2.5 Hz, 8.8 Hz, phenyl H), 7.05 (t, 1H, J=9.0 Hz,
phenyl H), 6.77 (br. t, 1H, NH), 5.10-5.13 (m, 1H, oxazolidinone H), 4.81 (d, 2H,
J=5.2 Hz, CH ), 4.20 (t, 1H, J=9.0 Hz, oxazolidinone H), 3.85 (dd, 1H, J=5.8 Hz, 9.4
Hz, oxazolidinone H), 3.81 (d, 1H, J=5.9 Hz, CH ), 3.55-3.59 (m, 4H, piperazinyl H),
2
2
-
1
2
3
1
6
3 3
.92-2.96 (m, 4H, piperazinyl H), 1.38 (s, 9H, C(CH ) ). IR (KBr pellet, cm ): ν
437, 2987, 2928, 1744, 1683, 1657, 1521, 1446, 1417, 1455, 1368, 1317, 1290,
+
227, 1190, 1063, 1029. MS 503.2 (M ). Anal calcd for C23
H
30FN
7
O
5
: C: 54.86, H:
.01, N: 19.47 found C: 54.85, H: 6.16, N: 19.19.
o
A mixture of 6a (3.40 g, 6.75 mmol) in DCM (7 mL) and TFA (7 mL) at 0 C was
stirred to r.t. overnight. The reaction mixture was concentrated on a rotavap to give a
semisolid 6g, which was triturated with a mixture of THF-Et
2
O 1:1 ratio to give 15 as
): δ 8.16 (s,1H,
O), 7.76 (s,1H, triazolyl H),
.42 (dd, 1H, J=2.5 Hz, 14.7 Hz, phenyl H), 7.14 (dd,1H, J=2.3 Hz, 8.8 Hz, phenyl
H), 7.06 (t, 1H, J=9.4 Hz, phenyl H), 5.11-5.15 (m, 1H, oxazolidinone H), 4.83 (d ,
H, J=5.0 Hz, CH ), 4.20 (t, 1H, J=9.2 Hz, oxazolidinone H), 3.92-3.94 (m, 2H,
piperazinyl H), 3.86 (dd, 1H, J=5.7 Hz, 9.3 Hz, oxazolidinone H), 3.66 (m, 2H ,
1
a white solid (3.49 g, quant yield). H-NMR (DMSO-d
6
, 600 MH
Z
triazolyl H), 8.03 (br. d, 2H, NH, exchangeable with D
2
7
2
2
-1
piperazinyl H), 2.95-3.00 (br. d, 4H, piperazinyl H). IR (KBr pellet, cm ): ν 3425,
+
2
975, 2930, 1760, 1678, 1521, 1486, 1430, 1204, 1136, 1024. MS 405.01 (M + H
1
1

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minus CF
purification.
.2.2. (R)-2-(4-(2-Fluoro-4-(5-((4-methyl-1H-1,2,3-triazol-1-yl)methyl)-2-oxo-
3
CO
2
). This product was used for subsequent reactions without further
5
oxazolidin-3-yl)phenyl)piperazin-1-yl)-2-oxoethanaminium 2,2,2-trifluoroacetate (16)
In a similar manner, compound 6b was prepared from 4-(2-fluoro-4-(5-((4-methyl-
1
H-1,2,3-triazol-1-yl)methyl)-2-oxooxazolidin-3-yl)phenyl)piperazin-1-ium 2,2,2-
trifluoroacetate (14; 1.0 gm, 2.12 mmol) as reported for 6a. Recrystallization (ethyl
o
1
acetate - hexane) gave 6b as a white solid (900 mg, yield, 83 %), mp- 175-177 C. H-
NMR (DMSO-d , 600 MHz): δ 7.86 (s, 1H, triazolyl H), 7.43 (dd, 1H, J=2.5 Hz, 14.7
Hz, phenyl H), 7.13 (dd, 1H J=2.5 Hz, 9.0 Hz, phenyl H), 7.06 (t, 1H, J=9.0, Hz,
phenyl H), 6.77 (br. t, 1H, NH, exchangeable with D O), 5.07-5.10 (m, 1H,
oxazolidinone H), 4.74 (d, 2H, J=5.2 Hz, CH ), 4.19 (t, 1H, J=9.0 Hz, oxazolidinone
H), 3.82-3.85 (m, 3H, CH and oxazolidinone H), 3.55-3.59 (m, 4H, piperazinyl H),
.92-2.97 (m, 4H, piperazinyl H) 2.22 (s, 3H, triazolyl CH ), 1.39 (s, 9H, C(CH ) ).
6
2
2
2
2
3
3 3
-1
IR (KBr pellet, cm ): ν 3444, 2977, 2932, 1741, 1708, 1668, 1517, 1427, 1440, 1455,
+
1
367, 1339, 1283, 1230, 1165, 1049, 1034. MS 517.4 (M ). Anal calcd for
24 7 5
C H32FN O : C: 55.70, H: 6.23, N: 18.94 found C: 55.74, H: 6.52, N: 18.74.
Compound 6b (2.77 g, 5.22 mmol) was then converted to 16 by a similar procedure
1
reported for 15 to give the title compound 16 as a solid (2.68 g, quant yield). H-NMR
(DMSO-d
6 2
, 600 MHz): δ 7.70-7.82 (m, 3H, amine +NH3, exchangeable with D O),
7
.64 (s, 1H, triazolyl H), 7.21 (dd, 1H, J=2.6 Hz, 14.7 Hz, phenyl H), 6.93 (dd, 1H,
J=2.1 Hz, 8.6 Hz, phenyl H), 6.84 (t, 1H, J=9.5 Hz, phenyl H), 4.86-4.88 (m, 1H,
oxazolidinone H), 4.52 (d, 2H, J=5.2 Hz, CH ), 3.97 (t, 1H, J=9.2 Hz, oxazolidinone
2
H), 3.71 (q, 2H, J=5.7 Hz, 11.4 Hz, CH ), 3.61 (dd, 1H, J=5.9 Hz, 9.3 Hz,
2
oxazolidinone H), 3.4-3.5 (m, 4H, piperazinyl H), 2.7-2.8 (m, 4H, piperazinyl H),
1
2

ACCEPTED MANUSCRIPT
+
-1
2
2
.00 (s, 3H, triazolyl CH
3
). Full MS 418.75 (M +H). IR (KBr pellet, cm ): ν 3444,
+
977, 2932, 1760, 1678, 1521, 1486, 1430, 1204, 1136, 1024. MS 419.06 (M + H
3 2
minus CF CO ). This product was used for subsequent reactions without further
purification.
5
.2.3. General procedure for the synthesis of the N-substitued-glycinyl derivatives
(6c-x)
The final compounds 6c-x were prepared from a solution of compound 15 or 16 in
DCM and / or CH CN and TEA (1.5 mL) treated with 1.1 eq. of suitable acid
3
anhydride or acid chloride or an activated acid (activated by reaction with DCC or 1-
[
3-(diethylamine)propyl]-3-ethyl carbodiimide hydrochloride and 1-hydroxy-
o
benzotriazole or by oxalyl chloride) or the arylsulfonyl chloride under stirring at 0 C.
Stirring was continued to r.t. overnight and the reaction mixture was concentrated on
a rotovap to give a crude, which was dissolved in DCM (60 mL), washed successively
with water, dilute aq. Na CO solution, water, dried (anhydrous Na SO ), filtered and
2
3
2
4
concentrated to obtain a crude product. The purification of the crude was performed
either by silica gel column chromatography and/or recrystallized from suitable
organic solvents to give the final products.
5
.2.3.1. (R)-N-(2-(4-(4-(5-((1H-1,2,3-Triazol-1-yl)methyl)-2-oxooxazolidin-3-yl)-2-
fluoro-phenyl piperazin-1-yl)-2-oxoethyl)acetamide (6c)
Compound 6c was prepared via the general procedure from 15 (500 mg, 0.97 mmol)
and acetic anhydride (200 mg, 0.18 mL, 1.94 mmol) in TEA, DCM (5 mL) and
CH CN (5 mL) to give a crude gum. Purification by silica gel column
3
chromatography (EtOAc-MeOH 9:1) afforded the title compound 6c as a white solid
1
3

ACCEPTED MANUSCRIPT
1
(
210 mg, yield, 49%), mp- 205-207 °C. H-NMR (DMSO-d
6
, 600 MHz): δ 8.16 (s,
O), 7.76 (s, 1H,
1
H, triazolyl H), 7.99 (t, 1H, J=5.5 Hz, NH, exchangeable with D
2
triazolyl H), 7.42 (dd, 1H, J=2.5 Hz, 14.7 Hz, phenyl H), 7.13 (dd, 1H, J=2.3 Hz, 8.8
Hz, phenyl H), 7.06 (t, 1H, J=9.3 Hz, phenyl H), 5.09-5.14 (m, 1H, oxazolidinone H),
4
.82 (d, 2H, J=5.1 Hz, CH ), 4.20 (t, 1H, J= 9.2 Hz, oxazolidinone H), 3.97 (d, 2H,
2
J=5.5 Hz, CH
2
), 3.85 (dd, 1H, J=5.7 Hz, 9.3 Hz oxazolidione H), 3.56-3.61 (br. d, 4H,
CO). IR (KBr
piperazinyl H), 2.92-2.98 (m, 4H, piperazinyl H), 1.87 (s, 3H, CH
3
-1
pellet, cm ): ν 3370, 2916, 2840, 1763, 1746, 1633, 1517, 1435, 1328, 1234, 1163,
+
1
113, 1034. MS 445.2 (M ). Anal calcd for C H FN O : C: 53.93, H: 5.43, N: 22.01
20
24
7
4
found C: 53.96, H: 5.08, N: 21.97
5
.2.3.2. (R)-N-(2-(4-(2-Fluoro-4-(5-((4-methyl-1H-1,2,3-triazol-1-yl)methyl)-2-oxo-
oxazolidin -3-yl)phenyl)piperazin-1-yl)-2-oxoethyl)acetamide (6d)
Compound 6d was prepared via the general procedure from 16 (500 mg, 0.94 mmol)
and acetic anhydride (190 mg, 0.18 mL, 1.88 mmol) in TEA and DCM (5 mL) and
3
CH CN (5 mL) to give the crude solid (470 mg). Purification by silica gel column
chromatography (EtOAc ꢀ EtOAc-methanol 9:1) gave 6d as a white solid (370 mg,
1
yield, 86%), mp- 215-217°C. H-NMR (DMSO-d
6
, 600 MHz): δ 7.99 (t, 1H, J= 6.0
Hz, NH, exchangeable with D O), 7.86 (s, 1H, triazolyl), 7.43 (dd, 1H, J=2.5 Hz, 14.7
2
Hz, phenyl), 7.14 (dd, 1H, J=2.7 Hz, 10.3 Hz, phenyl), 7.06 (t, 1H, J= 9.6, phenyl),
5
.05-5.10 (m, 1H, oxazolidinone H), 4.74 (d, 2H, J= 5.2 Hz, CH
Hz, oxazolidinone H), 3.97 (d, 2H, J=5.5 Hz, CH ), 3.83 (dd, 1H, J=5.9 Hz, 9.6 Hz
oxazolidione H), 3.56-3.61 (m, 4H, piperazinyl H), 2.92-2.98 (m, 4H, piperazinyl H),
2
), 4.19 (t, 1H, J= 9.3
2
-
1
2
2
.22 (s, 3H, triazolyl CH ), 1.87 (s, 3H, CH CO). IR (KBr pellet, cm ): ν 3364, 3341,
3 3
976, 2896, 2857, 1749, 1640, 1518, 1475, 1442, 1415, 1327, 1232, 1211, 1161,
1
4

ACCEPTED MANUSCRIPT
+
1
2
136, 1111, 1054. MS 459.4 (M ). Anal calcd for C21
7 4
H26FN O : C: 54.89, H: 5.70, N:
1.34 found C: 54.99, H: 6.00, N: 20.99
5
.2.3.3. (R)-2,2,2-Trifluoro-N-(2-(4-(2-fluoro-4-(5-((4-methyl-1H-1,2,3-triazol-1-
yl)methyl)-2-oxooxazolidin-3-yl)phenyl)piperazin-1-yl)-2-oxoethyl)acetamide (6e)
Compound 6e was prepared via the general procedure from 16 (400 mg, 0.75 mmoL)
and trifluoroacetic anhydride (236 mg, 159 µL, 1.125 mmol) in TEA and CH
mL) to give a crude solid (330 mg). Purification by silica gel column chromatography
EtOAc ꢀ EtOAc-methanol 10:1) gave 6e as a white powder (50 mg, yield 13%),
3
CN (10
(
o
1
mp- 205-207 C. H-NMR (DMSO-d
exchangeable with D O), 7.86 (s, 1H, triazolyl H), 7.43 (dd, 1H, J=2.4 Hz, 14.3 Hz,
phenyl H), 7.14 (dd, 1H, J=2.3 Hz, 8.8 Hz, phenyl H), 7.07 (t, 1H, J=8.8 Hz, phenyl
H), 5.06-5.09 (m, 1H, oxazolidinone H), 4.64-4.74 (m, 2H, CH ), 4.18 (t, 1H, J=10.7
Hz, oxazolidinone H) 4.11 (s, 2H, CF CONHCH ), 3.80-3.90 (m, 5H, oxazolidinone
6
, 600 MHz): δ 9.54 (br. s, 1H, NH,
2
2
3
2
&
3
piperazinyl H), 2.94-3.00 (br, 4H, piperazinyl H), 2.20 (s, 3H, triazolyl CH ). IR
-1
(
KBr pellet, cm ): ν 3524, 2919, 1741, 1724, 1653, 1518, 1517, 1436, 1336, 1228,
+
1
185, 1162, 1035. MS 513.2 (M ). Anal calcd for C21
H
23
F
4
N
7
O
4
: C: 49.12, H: 4.52,
N: 19.10; found C: 48.92, H: 4.62, N: 19.20.
5
.2.3.4. (R)-2,2-Dichloro-N-(2-(4-(2-fluoro-4-(5-((4-methyl-1H-1,2,3-triazol-1-
yl)methyl)-2-oxooxazolidin-3-yl)phenyl)piperazin-1-yl)-2-oxoethyl)acetamide (6f)
Compound 6f was prepared via the general procedure from 16 (400 mg, 0.75 mmol)
and dichloroacetyl chloride (160 mg, 1.28 mmol) in TEA and CH
3
CN (20 mL) to
give a crude solid (350 mg). Recrystallization (THF) gave 6f as a white solid (190
o
1
6
mg, yield 48%), mp- 206-208 C. H-NMR (DMSO-d , 600 MHz): δ 8.67 (t, 1H,
1
5

ACCEPTED MANUSCRIPT
J=5.4 Hz, NH, exchangeable with D
2
O), 7.56 (s, 1H, triazolyl H), 7.43 (dd, 1H, J=3.2
Hz, 15.6 Hz, phenyl H), 7.14 (dd, 1H, J=3.2 Hz, 10.6 Hz, phenyl H), 7.07 (t, 1H,
J=10.5 Hz, phenyl H), 6.68 (s, 1H, Cl
2
CH), 5.06-5.09 (m, 1H, oxazolidinone H), 4.74
(
d, 2H, J=5.5 Hz, CH ), 4.19 (t, 1H, J=10.5 Hz, oxazolidinone H) 4.12 (d, 2H, J=5.2
2
Hz, Cl CONHCH ), 3.83 (dd, 1H, J=5.9 Hz, 9.2 Hz, oxazolidinone H), 3.56-3.63 (br.
2
2
4
3
H, piperazinyl H), 2.94-3.00 (br, 4H, piperazinyl H), 2.22 (s, 3H, triazolyl CH ). IR
-1
(
KBr pellet, cm ): ν 3389, 3281, 2919, 1745, 1704, 1627, 1516, 1445, 1418, 1327,
+
1
4
233, 1107, 1031. MS 528.96 (M + H). Anal calcd for C21
2 7 4
H24Cl FN O : C: 47.74, H:
.58, N: 18.56; found C: 47.88, H: 4.78, N: 18.80.
5
.2.3.5. (R)-Ethyl 3-((2-(4-(4-(5-((1H-1,2,3-triazol-1-yl)methyl)-2-oxooxazolidin-3-
yl)-2-fluorophenyl)piperazin-1-yl)-2-oxoethyl)amino)-3-oxopropanoate (6g)
Compound 6g was prepared via the general procedure from 15 (700 mg,1.35 mmol)
and mono ethyl malonate (270 mg, 240 µL, 2.02 mmol) activated by oxalyl chloride
(
1.33 g, 910 µL, 10.50 mmol), in TEA, DCM (5 mL) and CH CN (25 mL) to give a
3
crude solid (750 mg). Purification by silica gel column chromatography (EtOAc-
MeOH 10:1 ꢀ 9:2), gave the title compound as white powder (210 mg, yield 30%),
o
1
mp- 198-200 C. H-NMR (DMSO-d
6 Z
, 600 MH ): δ 8.26 (t, 1H, J=5.2 Hz, NH,
exchangeable with D O), 8.16 (s, 1H, triazolyl H), 7.76 (s, 1H, triazolyl H), 7.42 (dd,
2
1
1
H, J=2.5 Hz, 14.7 Hz, phenyl H), 7.13 (dd,1H ,J=2.3 Hz, 8.8 Hz, phenyl H), 7.06 (t,
H, J=9.3 Hz, phenyl H), 5.10-5.14 (m, 1H, oxazolidinone H), 4.82 (d, 2H, J=5.1 Hz,
CH
2
), 4.20 (t, 1H, J=9.2 Hz, oxazolidinone H), 4.07 (q, 2H, J=7.1 Hz, CH
2
), 4.03 (d,
2
H, J=5.3 Hz, CH
2
), 3.86 (dd, 1H, J=5.9 Hz, 9.4 Hz, oxazolidinone H), 3.58-3.64 (br.
t, 2H, piperazinyl H), 3.55-3.58 (br. t, 2H, piperazinyl H), 2.96-3.00 (br. t, 2H,
piperazinyl H), 2.93-2.96 (br. t, 2H, piperazinyl H), 1.17 (t, 3H, J=7.1 Hz, CH ). IR
3
1
6

ACCEPTED MANUSCRIPT
-1
(
KBr pellet, cm ): ν 3429, 2911, 2859, 1753, 1638, 1518, 1473, 1442, 1417, 1329,
+
1
5
282, 1225, 1192, 1163, 1111, 1034. MS 517.2 (M ). Anal calcd for C23
7 6
H28FN O : C:
3.38, H: 5.45, N: 18.95; found C: 53.20, H: 5.12, N: 18.68.
5
.2.3.6. (R)-Ethyl 3-((2-(4-(2-fluoro-4-(5-((4-methyl-1H-1,2,3-triazol-1-yl)methyl)-2-
oxo oxazolidin-3-yl)phenyl)piperazin-1-yl)-2-oxoethyl)amino)-3-oxopropanoate (6h)
Compound 6h was prepared via the general procedure from 16 (500 mg, 0.94 mmol)
and mono ethyl malonate (190 mg, 170 µL, 1.41 mmol) activated by oxalyl chloride
(
930 mg, 640 µL, 7.3 mmol), in TEA, DCM (5 mL) and CH CN (20 mL) to give a
3
crude solid (560 mg). Purification by silica gel column chromatography (EtOAc-
MeOH 10:1) gave the title compound as white powder (130mg, yield 26%), mp- 205-
o
1
2
07 C. H-NMR (DMSO-d
with D O), 7.86 (s, 1H, triazolyl H), 7.44 (dd, 1H, J=2.5 Hz, 14.7 Hz, phenyl H), 7.14
dd,1H ,J=2.3 Hz, 8.8 Hz, phenyl H), 7.06 (t, 1H, J=9.3 Hz, phenyl H), 5.07-5.09 (m,
H, oxazolidinone H), 4.74 (d, 2H, J=5.3 Hz, CH ), 4.19 (t, 1H, J=9.1 Hz,
6 Z
, 600 MH ): δ 8.27 (t, 1H, J=5.2 Hz, NH, exchangeable
2
(
1
2
oxazolidinone H), 4.07 (q, 2H, J=7.1 Hz, CH
2
2
), 4.04 (d, 2H, J=5.2 Hz, CH ), 3.83 (dd,
1
3
H, J=5.9 Hz, 9.3 Hz, oxazolidinone H), 3.60-3.64 (br. t, 2H, piperazinyl H), 3.56-
.60 (br. t, 2H, piperazinyl H), 2.96-3.00 (br. t, 2H, piperazinyl H), 2.93-2.96 (br. t,
H, piperazinyl H), 2.22(s, 3H, CH ), 1.18 (t, 3H, J=7.1 Hz, CH ). IR (KBr pellet, cm
-
2
3
3
1
): ν 3429, 2911, 2859, 1753, 1638, 1518, 1473, 1442, 1417, 1329, 1282, 1225, 1192,
+
1
1
163, 1111, 1034. MS 531.3 (M ). Anal calcd for C24
7 6
H30FN O : C: 54.23, H: 5.69, N:
8.45; found C: 53.98, H: 5.72, N: 18.15.
5
.2.3.7. N-(2-(4-(4-((R)-5-((1H-1,2,3-Triazol-1-yl)methyl)-2-oxooxazolidin-3-yl)-2-
fluoro- phenyl)piperazin-1-yl)-2-oxoethyl)tetrahydrofuran-2-carboxamide (6i)
1
7

ACCEPTED MANUSCRIPT
Compound 6i was prepared via the general procedure from 15 (500 mg,0.97 mmol)
and tetrahydrofuran-2-carboxylic acid (340 mg, 280 µL, 2.91 mmol) activated by
oxalyl chloride (3.69 mg, 2.54 mL, 29.1 mmol), in TEA, DCM (5 mL) and CH
3
CN
(
10 mL) to give a crude solid (400 mg). Recrystallization (CH CN-Et O) gave 6i as a
3
2
o
1
solid (150 mg, yield 31%), mp- 198-200 C. H-NMR (DMSO-d , 600 MH ): δ 8.16
6
Z
(
s, 1H, triazolyl H), 7.76 (s, 1H, triazolyl H), 7.74 (t, 1H, J=5.3 Hz, NH, exchangeable
with D O), 7.42 (dd, 1H ,J=3.74 Hz, 15.66 Hz, phenyl H), 7.13 (dd, 1H,J=3.24 Hz,
.96 Hz, phenyl H), 7.06 (t, 1H, J=9.72 Hz, phenyl H), 5.12-5.13 (m, 1H,
2
9
oxazolidinone H), 4.82 (d, 2H, J=4.0 Hz, CH ), 4.26 (dd, 1H, J=5.3 Hz, 9.0 Hz,
2
tetrahydrofuran H), 4.19 (t, 1H, J=8.9 Hz, oxazolidinone H), 4.00 (dd, 2H, J=4.9 Hz,
1
2
6.7 Hz, CH ), 3.91 (q, 1H, J=8.9 Hz, tetrahydrofuran H), 3.86 (dd, 1H, J=6.3 Hz, 9.8
Hz, oxazolidinone H), 3.79 (q, 1H, J=6.6 Hz, tetrahydrofuran H), 3.56-3.62 (br. d, 4H,
piperazinyl H), 2.92-2.99 (br. d, 4H, piperazinyl H), 2.11-2.12 (m, 1H,
-1
tetrahydrofuran H), 1.82-1.90 (m, 3H, tetrahydrofuran H). IR (KBr pellet, cm ): ν
3
5
408, 2871, 1747, 1649, 1518, 1437, 1330, 1279, 1232, 1164, 1111, 1075, 1032. MS
+
01.2 (M ). Anal calcd for C23
H28FN
7
O
5
: C: 55.08, H: 5.63, N: 19.55; found C: 54.94,
H: 5.47, N: 19.25.
5
.2.3.8. N-(2-(4-(2-Fluoro-4-((R)-5-((4-methyl-1H-1,2,3-triazol-1-yl)methyl)-2-oxo-
oxazolidin -3-yl)phenyl)piperazin-1-yl)-2-oxoethyl)tetrahydrofuran-2-carboxamide
6j)
(
Compound 6j was prepared via the general procedure from 16 (800 mg, 1.50 mmol)
and tetrahydrofuran-2-carboxylic acid (200 mg, 1.80 mmol) activated by 1-hydroxy-
benzotriazole (300 mg, 2.16 mmol) and 1-[3-(diethylamine) propyl)3-ethyl
carbodimide hydrochloride (680 mg, 3.6 mmol), in TEA, DCM / CH CN (25-25 mL)
3
1
8

ACCEPTED MANUSCRIPT
to give a crude solid (280 mg). Purification by silica gel column (EtOAc-MeOH
1
0:1), gave the title compound as a white powder (60 mg, yield 8%), mp- 100-102
o
1
C. H-NMR (DMSO-d
6
, 600 MHz): δ 7.86 (s, 1H, triazolyl H), 7.74 (t, 1H, J=5.4 Hz,
NH, exchangeable with D O), 7.43 (dd, 1H, J=2.5 Hz, 14.7 Hz, phenyl H), 7.14 (dd,
2
1
H, J=2.5 Hz, 9.6 Hz, phenyl H), 7.06 (t, 1H, J=9.4 Hz, phenyl H), 5.05-5.12 (m, 1H,
oxazolidinone H), 4.73 (d, 2H, J=5.0 Hz, CH ), 4.18-4.28 (m, 2H), 3.78-4.04 (m, 5H),
.55-3.62 (br, 4H, piperazinyl H), 2.94-3.00 (br, 4H, piperazinyl H), 2.20 (s, 3H,
2
3
-1
CH
3
), 2.08-2.13 (m, 1H), 1.81-1.87 (m, 3H). IR (KBr pellet, cm ): ν 3524, 2923,
+
1
745, 1654, 1517, 1444, 1331, 1332, 1233, 1133, 1039. MS 517.02 (M + H). Anal
7 5
calcd for C24H30FN O : C: 55.91, H: 5.87, N: 19.02; found C: 55.71, H: 5.78, N:
1
8.91.
5
.2.3.9. (R)-N-(2-(4-(4-(5-((1H-1,2,3-Triazol-1-yl)methyl)-2-oxooxazolidin-3-yl)-2-
fluorophenyl)piperazin-1-yl)-2-oxoethyl)benzamide (6k)
Compound 6k was prepared via the general procedure from 15 (500 mg, 0.97 mmol)
and benzoyl chloride (200 mg, 0.17 mL, 1.46 mmol) in TEA and CH
3
CN (5 mL) to
give a crude solid (580 mg). Purification by silica gel column chromatography
(EtOAc-MeOH 10: 0.5) afforded 6k as a white solid (390 mg, yield 79%), mp- 228-
1
2
30 °C. H-NMR (DMSO-d ,600 MHz): 8.59 (t, 1H, J=5.2 Hz, NH, exchangeable
6
with D
2
O), (s, 1H, triazolyl H), 7.87-7.89 (m, 2H, phenyl H), 7.77 (s, 1H, triazolyl H),
.53-7.56 (m, 1 H, phenyl H), 7.48-7.50 (m, 2H, phenyl H), 7.43 (dd, 1H, J= 2.5 Hz,
4.6 Hz, phenyl H), 7.14 (dd, 1H, J=2.4 Hz, 8.8 Hz, phenyl H), 7.08 (t, 1H, J=9.4 Hz,
), 4.21 (t,
H, J=9.2, oxazolidinone H), 4.18 (d, 2H, J=5.7 Hz, CH ), 3.86 (dd, 1H, J=5.7 Hz, 9.3
7
1
phenyl H), 5.10-5.14 (m, 1H, oxazolidinone H), 4.83 (d, 2H, J=5.1 Hz , CH
2
1
2
Hz, oxazolidinone H), 3.65 (br d, 4H, piperazinyl H), 2.98 (br d, 4H, piperazinyl H).
1
9

ACCEPTED MANUSCRIPT
1
3
C-NMR (DMSO-d
6
): δ 167.08, 166.36, 155.80, 153.50, 153.37, 135.51, 134.13,
1
1
2
33.42, 133.35, 131.33, 128.35, 127.25, 125.90, 119.81, 119.77, 114.29, 106.88,
-1
06.62, 70.81, 54.93, 51.73, 50.62, 50.26, 47.09, 44.18. IR (KBr pellet, cm ): ν 3357,
+
992, 2898, 1731, 1650, 1516, 1429, 1328, 1232, 1114, 1031. MS 507.5 (M ). Anal
7
calcd for C25H26FN O4: C: 59.16, H: 5.16, N: 19.32 found C: 58.90, H: 4.98, N:
1
8.98.
5
.2.3.10. (R)-N-(2-(4-(2-Fluoro-4-(5-((4-methyl-1H-1,2,3-triazol-1-yl)methyl)-2-oxo-
oxazolidin-3-yl)phenyl)piperazin-1-yl)-2-oxoethyl)benzamide (6l)
Compound 6l was prepared via the general procedure from 16 (500 mg, 0.94 mmol)
and benzoyl chloride (200 mg, 0.17 mL, 1.41 mmol) in TEA and CH
3
CN (5 mL) to
give a crude solid (580 mg). Purification by silica gel chromatography (EtOAc-MeOH
1
2
0:0.5 ꢀ EtOAc-MeOH 10:1) gave 6l as a white solid (400 mg, yield 82%), mp- 205-
1
07 °C. H-NMR (DMSO-d , 600 MHz): δ 8.60 (t, 1H, J=5.8, NH, exchangeable with
6
D
2
O), 7.86-7.88 (m, 3H, phenyl H, triazolyl H), 7.53-7.56 (m, 1H, phenyl H), 7.47-
.50 (m, 2H, phenyl H), 7.44 ( dd, 1H, J=2.6 Hz, 14.9 Hz, phenyl H), 7.15 (dd, 2H,
J=2.4 Hz, 9.5 Hz, phenyl H), 7.08 (t, 1H, J=9.5 Hz, phenyl), 5.06-5.11 (m, 1H,
oxazolidinone H), 4.74 (d, 2H, J=5.4 Hz, CH ), 44.18-4.21 (m, 3H, oxazolidinone H,
CH ), 3.84 (dd, 4H, J=5.1 Hz, 9.6 Hz oxazolidinone H), 3.62-3.67 (br d, 4H,
7
2
2
3
piperazinyl H), 2.94-2.95 (br d, 4H, piperazinyl H), 2.22 (s,3H, triazolyl CH ). IR
-1
(
KBr pellet, cm ): ν 3428, 2918, 1745, 1636, 1517, 1465, 1425, 1337, 1224, 1135,
+
1
041. MS 521.1 (M ). Anal calcd for C26
H
7
28FN O
4
: C: 59.88, H: 5.41, N: 18.80 found
C: 59.64, H: 5.40, N: 18.83.
2
0

ACCEPTED MANUSCRIPT
5
.2.3.11. (R)-N-(2-(4-(4-(5-((1H-1,2,3-Triazol-1-yl)methyl)-2-oxooxazolidin-3-yl)-2-
fluorophenyl)piperazin-1-yl)-2-oxoethyl)-3,5-dinitrobenzamide (6m)
Compound 6m was prepared via the general procedure from 15 (500 mg, 0.97 mmol)
and 3,5-dinitrobenzoyl chloride (666 mg, 2.89 mmol) in TEA and CH CN (25 mL) to
3
give a yellow solid. Recrystallization (CH CN) gave the title compound as a yellow
3
o
1
solid (290 mg, yield 50%), mp- 199-201 C. H-NMR (DMSO-d
t, 1H, J=6.8 Hz, NH, exchangeable with D O), 9.08 (d,2H, J=2.1 Hz, nitrophenyl H),
.98 (t, 1H, J=2.2 Hz, nitrophenyl H), 8.17 (s, 1H, triazolyl H), 7.77 (s, 1H, triazolyl
6 Z
, 600 MH ): δ 9.46
(
2
8
H), 7.43 (dd,1H, J=2.6 Hz,15.0 Hz, phenyl H), 7.14 (dd, 1H,J=3.0 Hz,8.2 Hz, phenyl
H),7.08 (t, 1H, J=8.8 Hz, Phenyl H), 5.11-5.14 (m, 1H, oxazolidinone H), 4.83 (d, 2H,
2 2
J=5.1Hz, CH ), 4.28 (d, 2H, J=5.2 Hz , CH ), 4.21 (t, 1H, J=9.2 Hz, oxazolidinone
H),3.86 (dd, 1H, J=5.4 Hz, 8.7 Hz, oxazolidinone H), 3.64-3.69 (br. d, 4H, piperazinyl
-1
H), 2.95-3.04 (br. d, 4H, piperazinyl H). IR (KBr pellet, cm ): ν 3389, 2918, 1750,
1
678, 1651, 1539, 1428, 1338, 1299, 1234, 1200, 1176, 1105, 1076, 1031. MS 597.3
+
(
M ). Anal calcd for C H FN O : C: 50.25, H: 4.05, N: 21.10; found C: 50.17, H:
25
24
9
8
4
.02, N: 20.96.
5
.2.3.12. (R)-N-(2-(4-(2-Fluoro-4-(5-((4-methyl-1H-1,2,3-triazol-1-yl)methyl)-2-oxo-
oxazolidin-3-yl)phenyl)piperazin-1-yl)-2-oxoethyl)-3,5-dinitrobenzamide (6n)
Compound 6n was prepared via the general procedure from 16 (450 mg, 0.85 mmol)
and 3,5-dinitrobenzoyl chloride (290 mg, 1.28 mmol) in TEA and CH
give a reddish-yellow gum (620 mg). Purification by silica gel column
chromatography (EtOAc ꢀ EtOAc-MeOH 10:1) gave 6n as a solid (260 mg, yield
3
CN (10 mL) to
o
1
5
2%), mp- 234-236 C. H-NMR (DMSO-d
6
, 600 MHz): δ 9.46 (t, 1H, J=6.0 Hz, NH,
exchangeable with D O), 9.08 (s, 2H, J=2.2 Hz, phenyl H), 8.98 (t, 1H, J=2.1 Hz,
2
2
1

ACCEPTED MANUSCRIPT
phenyl H), 7.86 (s, 1H, triazolyl H), 7.44 (dd, 1H, J=2.5 Hz, 14.7 Hz, phenyl H), 7.15
(dd, 1H, J=2.7 Hz, 8.7 Hz, phenyl H), 7.09 (t, 1H, J=9.3 Hz, phenyl H), 5.08-5.10 (m,
1
4
H, oxazolidinone H), 4.74 (d, 2H, J=5.02 Hz, CH
2 2
), 4.29 (d, 2H, J=5.7 Hz, CH ),
.20 (t, 1H, J=9.1 Hz, oxazolidinone H), 3.84 (dd, 1H, J=5.9 Hz, 9.3 Hz,
oxazolidinone H), 3.65-3.68 (two br t, 4H, J=5.3 Hz, piperazine H), 2.95-3.04 (two br
-1
t, 4H, J=5.3 Hz, piperazine H), 2.23 (s, 3H, triazolyl CH
3
). IR (KBr pellet, cm ): ν
3
6
5
401, 3089, 2821, 1750, 1655, 1535, 1525, 1443, 1344, 1300, 1236, 1103, 1033. MS
+
12.2 (M + H). Anal calcd for C26
H
26FN
9
O
8
: C: 51.06, H: 4.29, N: 20.61; found C:
0.80, H: 4.62, N: 20.08.
5
.2.3.13. (R)-N-(2-(4-(4-(5-((1H-1,2,3-Triazol-1-yl)methyl)-2-oxooxazolidin-3-yl)-2-
fluorophenyl)piperazin-1-yl)-2-oxoethyl)nicotinamide (6o)
Compound 6o was prepared via the general procedure from 15 (500 mg,0.97 mmol)
and nicotinoyl chloride (515 mg, 2.89 mmol) in TEA and CH CN (10 mL) to give a
3
crude solid (580 mg). Recrystallization (MeOH-Et O) gave 6o as a solid (60 mg, yield
2
o
1
2
9%), mp- 198-200 C. H-NMR (DMSO-d
nicotinoyl H), 8.85 (br. t, 1H, NH, exchangeable with D
nicotinoyl H), 8.22 (d, 1H, J=7.9 Hz, nicotinoyl H), 8.17 (s, 1H, triazolyl H), 7.77 (s,
H, triazolyl H), 7.53 (dd,1H, J=4.1 Hz, 8.3 Hz, nicotinoyl H), 7.43 (dd, 1H, J=2.8
Hz, 14.6 Hz , phenyl H), 7.14 (dd, 1H, J=2.7 Hz, 9.1 Hz, phenyl H), 7.08 (t, 1H, J=8.7
Hz, phenyl H), 5.11-5.14 (m, 1H, oxazolidinone H), 4.83 (d, 2H, J=5.0 Hz , CH ),
.20-4.25 (m, 3H, CH & oxazolidinone H), 3.86 (dd, 1H, J=6.7 Hz, 9.0 Hz,
oxazolidinone H), 3.63-3.67 (br. d, 4H, piperazinyl H), 2.95-3.03 (br. d, 4H,
6
, 600 MH
Z
): δ 9.04 (d, 1H, J=1.8 Hz,
2
O), 8.73 (d, 1H, J=4.8 Hz,
1
2
4
2
-1
piperazinyl H). IR (KBr pellet, cm ): ν 3370, 2942, 1743, 1639, 1588, 1518, 1465,
+
1
444, 1420, 1335, 1284, 1230, 1201, 1162, 1107, 1078, 1026. MS 509.99 (M + H).
2
2

ACCEPTED MANUSCRIPT
8 4
Anal calcd for C24H25FN O : C: 56.69, H: 4.96, N: 22.04; found C: 56.78, H: 4.85, N:
2
2.21.
5
.2.3.14. (R)-N-(2-(4-(2-Fluoro-4-(5-((4-methyl-1H-1,2,3-triazol-1-yl)methyl)-2-oxo-
oxazolidin-3-yl)phenyl)piperazin-1-yl)-2-oxoethyl)nicotinamide (6p)
Compound 6p was prepared via the general procedure from 16 (400 mg, 0.75 mmol)
3
and nicotinoyl chloride (200 mg, 2.25 mmol) in TEA and CH CN (10 mL) to give a
crude solid (190 mg). Purification by silica gel column chromatography (EtOAc ꢀ
EtOAc-MeOH 10:1 ꢀ 10:2) afforded 6p as a while solid (110 mg, yield 28%), mp-
o
1
1
85-187 C. H-NMR (DMSO-d
6
, 600 MHz): δ 8.99 (s, 1H, triazolyl), 8.88 (t, 1H,
O), 8.70 (d, 1H, J=5.9 Hz, pyridyl H), 8.19-8.21
m 1H, pyridyl H), 7.83 (s, 1H, pyridyl H), 7.53 (dd, 1H, 7.5 Hz, 15.1 Hz, pyridyl H),
J=5.9 Hz, NH, exchangeable with D
2
(
7
.44 (dd, 1H, J=2.5 Hz, 14.7 Hz, phenyl H), 7.10 (dd, 1H, J=2.7 Hz, 8.8 Hz, phenyl
H), 7.05-7.11 (m, 2H, phenyl H), 5.08-5.10 (m, 1H, oxazolidinone H), 4.70-4.72 (m,
2
3
3
1
H, CH
2
), 4.18-4.24 (m, 3H, oxazolidinone H, ), 3.80-3.85 (m, 1H, oxazolidinone H),
.59-3.66 (br, 4H, piperazinyl H), 2.95-3.04 (two br s, 4H, piperazinyl H), 2.20 (s,
-1
H, triazolyl CH
3
). IR (KBr pellet, cm ): ν 3392, 2921, 1745, 1649, 1518, 1472,
+
420, 1334, 1228, 1033. MS 523.98 (M + H). Anal calcd for C25
H
27FN
8
O
4
: C: 57.46,
H: 5.21, N: 21.44; found C: 57.12, H: 5.40, N: 21.04.
5
.2.3.15. (R)-N-(2-(4-(4-(5-((1H-1,2,3-Triazol-1-yl)methyl)-2-oxooxazolidin-3-yl)-2-
fluorophenyl)piperazin-1-yl)-2-oxoethyl)thiophene-2-carboxamide (6q)
Compound 6q was prepared via the general procedure from 15 (500 mg,0.97 mmol)
and 2-thiophene- carbonyl chloride (424 mg, 2.89 mmol) in TEA and CH CN (10
3
3
mL) to give a crude solid. Recrystallization (CH CN) gave 6q as a crystalline solid
2
3

ACCEPTED MANUSCRIPT
o
1
(
320 mg, yield 61%), mp- 230-232 C. H-NMR (DMSO-d
6 Z
, 600 MH ): δ 8.62 (t, 1H,
J=5.7 Hz, NH, exchangeable with D O), 8.16 (s, 1H, triazolyl H), 7.62-7.82 (m, 3H,
2
triazolyl H & thiophene H), 7.43 (dd, 1H, J=2.5 Hz,14.7 Hz, phenyl H), 7.16 (dd, 1H,
J=3.8 Hz, 4.9 Hz, thiophene H), 7.13 (dd, 1H, J=2.3 Hz, 8.8 Hz, phenyl H), 7.07 (t,
1
H, J=9.4, Hz, phenyl H), 5.11-5.13 (m, 1H, oxazolidinone H), 4.83 (d, 2H, J=5.1 Hz,
CH ), 4.21 (t, 1H, J=9.2 Hz, oxazolidinone H), 4.15 (d, 2H, J=5.6 Hz, CH ), 3.86,(dd,
H, J=5.7 Hz, 9.3 Hz, oxazolidinone H), 3.63-3.65 (m, 4H, piperazinyl H), 2.94-3.01
2
2
1
1
3
(
br. d, 4H, piperazinyl H). C-NMR (DMSO-d
6
): δ 166.98, 161.34, 155.80, 153.50,
1
1
3
1
39.64, 135.50, 133.40, 133.35, 130.89, 128.36, 127.98, 125.90, 119.81, 114.27,
-1
06.88, 106.62, 70.81, 51.74, 50.62, 50.27, 47.10, 44.21. IR (KBr pellet, cm ): ν
422, 3368, 2915, 1735, 1635, 1518, 1441, 1335, 1281, 1227, 1200, 1164, 1104,
+
024. MS 513.2 (M ). Anal calcd for C23
H
7
24FN O
4
S: C: 53.79, H: 4.71, N: 19.09;
found C: 53.57, H: 4.64, N: 18.86.
5
.2.3.16. (R)-N-(2-(4-(2-Fluoro-4-(5-((4-methyl-1H-1,2,3-triazol-1-yl)methyl)-2-
oxooxazolidin-3-yl)phenyl)piperazin-1-yl)-2-oxoethyl)thiophene-2-carboxamide (6r)
Compound 6r was prepared via the general procedure from 16 (400 mg, 0.75 mmol)
and 2-thiophene carbonyl chloride (330 mg, 2.25 mmol) in TEA and CH
3
CN (10 mL)
to give a crude light yellow solid (580 mg). Recrystallization (CH CN) gave 6r as an
3
o
1
off-white solid (150 mg, yield, 37%), m.p. 212-215 C. H-NMR (DMSO-d
6
, 600
MH ): δ 8.62 (t, 1H, J=6.8 Hz , NH, exchangeable with D O), 7.86 (s, 1H, triazolyl
Z
2
H), 7.81 (dd, 1H, J=1.1 Hz, 3.7 Hz, thiophene H), 7.77 (dd, 1H, J=1.1 Hz, 5.0 Hz,
thiophene H), 7.44 (dd, 1H, J=2.5 Hz, 14.7 Hz, phenyl H), 7.13-7.17 (m, 2H, phenyl
H, thiophene H), 7.07 (t, 1H, J=9.3 Hz, phenyl H), 5.07-5.09 (m, 1H, oxazolidinone
2
H), 4.74 (d, 2H, J=5.0 Hz, CH ), 4.19 (t, 1H, J=9.1 Hz, oxazolidinone H), 4.15 (d, 2H,
2
4

ACCEPTED MANUSCRIPT
J=5.7 Hz, CH
2
), 3.84 (dd, 1H, J=5.9 Hz, 9.3 Hz, oxazolidinone H), 3.63-3.65 (dd, 4H,
2
piperazinyl H), 3.32 (dd, 1H, oxazolidinone H overlapping partly with D O signal),
-
1
2
3
.94-3.01 (br. d, 4H, piperazinyl H), 2.23 (s, 3H, triazolyl H). IR (KBr pellet, cm ): ν
+
428, 2920, 1740, 1633, 1523, 1475, 1429, 1338, 1232, 1204, 1051. MS 527.3 (M ).
Anal calcd for C H FN O S: C: 54.64, H: 4.97,N: 18.58, found C: 54.49, H: 4.90,
24
26
7
4
N: 18.35.
5
.2.3.17. (R)-N-(2-(4-(4-(5-((1H-1,2,3-Triazol-1-yl)methyl)-2-oxooxazolidin-3-yl)-2-
fluorophenyl)piperazin-1-yl)-2-oxoethyl)furan-2-carboxamide (6s)
Compound 6s was prepared via the general procedure from 15 (500 mg,0.97 mmol)
and 2-furoyl chloride (377 mg, 2.89 mmol) in TEA and CH
crude solid. Recrystallization (CH CN) gave 6s as a crystalline solid (230mg, yield
0%), mp- 198-200 C. H-NMR (DMSO-d , 600 MH ): δ 8.30 (t, 1H, J=5.6 Hz, NH,
exchangeable with D O), 8.16(s, 1H, triazolyl H), 7.86 (s, 1H , thiophene H), 7.76 ( s,
3
CN (10 mL) to give a
3
o
1
5
6
Z
2
1
H, triazolyl H), 7.43 (dd, 1H, J=2.5 Hz, 14.6 Hz, phenyl H), 7.12-7.14 (m, 2H, furan
H & phenyl H), 7.07 (t, 1H, J=9.3 Hz, phenyl H), 6.64 (dd, 1H, J=1.7 Hz, 3.4 Hz,
furan H), 5.10-5.14 (m, 1H, oxazolidinone H), 4.83 (d, 2H, J=5.1 Hz, CH ), 4.21(t,
H, J=9.2 Hz , oxazolidinone H), 4.13 (d,1H, J=5.4 Hz , CH ), 3.86 (dd, 1H, J=5.7
Hz, 9.3 Hz, oxazolidinone H), 3.60-3.63 br. s, 4H, piperazinyl H), 2.94-3.00 (br. s,
2
1
2
-
1
4
1
H, piperazinyl H). IR (KBr pellet, cm ): ν 3422, 3362, 2918, 1735, 1643, 1592,
+
516, 1440, 1337, 1225, 1200, 1166, 1105, 1068, 1026. MS 497.2 (M ). Anal calcd
7 5
for C23H24FN O : C: 55.53, H: 4.86, N: 19.71; found C: 55.34, H: 4.89, N: 19.51.
5
.2.3.18. (R)-N-(2-(4-(2-Fluoro-4-(5-((4-methyl-1H-1,2,3-triazol-1-yl)methyl)-2-
oxooxazolidin-3-yl)phenyl)piperazin-1-yl)-2-oxoethyl)furan-2-carboxamide (6t)
2
5

ACCEPTED MANUSCRIPT
Compound 6t was prepared via the general procedure from 16 (400 mg, 0.75 mmol)
3
and 2-furoyl chloride (290 mg, 2.25 mmol) in TEA and CH CN (10 mL) to give a
crude solid (620 mg). Recrystallization (CH
3
CN) gave the title compound as a with
o
1
powder (220 mg, yield 58%), mp- 206-208 C. H-NMR (DMSO-d , 600 MH ): δ
6
Z
8
7
.29 (t,1H, J=6.8 Hz , NH, exchangeable with D O) , 7.86 (d, 2H , triazolyl, furan H),
2
Z Z
.44 (dd, 1H, J=3.8 H , 13.7 H , phenyl H), 7.14 (dd, 2H, J=3.1, Hz, 10.5 Hz, phenyl
H, furan H), 7.08 (t, 1H, J=10.4 Hz, phenyl H), 6.64 (dd, 1H, J=1.8 Hz, 3.4 Hz, furan
H), 5.07-5.09 (m, 1H, oxazolidinone H), 4.74 (d, 2H, J=5.1 Hz, oxazolidinone H),
4
.19 (t, 1H, J=9.6 H , oxazolidinone H), 4.14 (d, 2H, J=5.4 Hz, CH ), 3.84 (dd, 1H,
Z 2
J=6.0 Hz, 13.1 Hz, oxazolidinione H), 3.63 (br, 4H, piperazinyl H), 2.94-3.00 (br. d,
-
1
4
1
H, piperazinyl H), 2.23 (s, 3H, triazolyl H). IR (KBr pellet, cm ): ν 3371, 2921,
+
741, 1642, 1596, 1518, 1469, 1429, 1339, 1232, 1203, 1022. MS 511.51 (M ). Anal
7 5
calcd for C24H26FN O : C: 56.36, H: 5.12, N: 19.17; found C: 56.20, H: 5.02, N:
1
8.90.
5
.2.3.19. (R)-N-(2-(4-(4-(5-((1H-1,2,3-Triazol-1-yl)methyl)-2-oxooxazolidin-3-yl)-2-
fluorophenyl)piperazin-1-yl)-2-oxoethyl)-5-nitrofuran-2-carboxamide (6u)
Compound 6u was prepared via the general procedure from 15 (600 mg,1.16 mmol)
5
-nitrofuran-2-carboxylic acid (360 mg, 2.32 mmol) activated by oxalyl chloride; in
TEA and CH CN (20 mL) to give a crude yellow solid (1.60 g). Recrystallization
3
o
1
(
DCM) gave 6u as a yellow solid (620 mg, yield 35%), mp- 210-213 C. H-NMR
DMSO-d , 600 MH ): δ 8.93 (t,1H, J=5.8 Hz, NH, exchangeable with D O), 8.17 (s,
H, triazolyl H), 7.76 (d, 2H, J=3.4 Hz, furan H, triazolyl H), 7.47 (d, 1H, J=3.9 Hz,
(
6
Z
2
1
furan H), 7.43 (dd, 1H, J=2.5 Hz, 14.7 Hz, phenyl H), 7.14 (dd, 1H, J=2.3 Hz, 8.8 Hz,
phenyl H), 7.07 (t, 1H, J=9.3 Hz, phenyl H), 5.11-5.13 (m, 1H, oxazolidinone H),
2
6

ACCEPTED MANUSCRIPT
4
.83 (d, 2H, J=5.1 Hz, CH
2 2
), 4.20 (m, 3H, CH , oxazolidinone H), 3.85 (dd, 1H, J=5.7
Hz, 9.3 Hz, oxazolidinone H), 3.63 (br. s, 4H, piperazinyl H), 2.98 (br. d, 4H,
13
piperazinyl H). C-NMR (DMSO-d
6
): δ 166.23, 156.25, 155.34, 153.73, 153.45,
1
7
2
47.96, 135.42, 133.31, 125.38, 119.76, 115.78, 114.25, 113.41, 106.81, 106.64,
-1
0.75, 51.69, 51.69, 50.53, 50.16, 47.06, 45.48, 44.14. IR (KBr pellet, cm ): ν 3422,
+
928, 1742, 1665, 1520, 1446, 1407, 1348, 1292, 1239, 1135, 1033. MS 542.2 (M ).
8 7
Anal calcd for C23H23FN O : C: 50.92, H: 4.27, N: 20.66; found C: 50.55, H: 4.55, N:
2
0.46.
5
.2.3.20. (R)-N-(2-(4-(2-Fluoro-4-(5-((4-methyl-1H-1,2,3-triazol-1-yl)methyl)-2-oxo-
oxazolidin-3-yl)phenyl)piperazin-1-yl)-2-oxoethyl)-5-nitrofuran-2-carboxamide (6v)
Compound 6v was prepared via the general procedure from 16 (500 mg,0.94 mmol)
and 5-nitrofuran carboxylic acid (290 mg, 1.88 mmol) activated by oxalyl chloride, in
TEA and CH CN (10 mL) to give a crude yellow solid (500 mg). Purification by
3
silica gel column chromatography (EtOAc, ꢀEtOAc-MeOH 10:1) gave 6v as a
o
1
yellow solid (240 mg, yield 48%), mp- 160-162 C. H-NMR (DMSO-d
δ 8.94 (t,1H J=5.6 Hz, NH, exchangeable with D O), 7.86 (s, 1H, triazolyl H), 7.77
d, 1H, J=3.9 Hz, furan H), 7.47(d, 1H J=3.9 Hz, furan H), 7.44 (dd, 1H, J=2.5 Hz,
6 Z
, 600 MH ):
2
(
1
4.7 Hz, phenyl H), 7.15 (dd, 1H, J=2.3 Hz, 8.8 Hz, phenyl H), 7.08 (t, 1H, J=9.5 Hz,
), 4.18-
, oxazolidinone H), 3.84 (dd, 1H, J=5.9 Hz, 9.5 Hz, oxazolidinone
H), 3.62-3.64 (m, 4H, piperazinyl H), 3.01(dd, J=4.9 Hz, piperazinyl H), 2.95 (dd,
phenyl H), 5.07-5.10 (m, 1H, oxazolidinone H), 4.73 (d, 2H, J=5.3 Hz, CH
.21 (m, 3H, CH
2
4
2
1
3
J=4.9 Hz, piperazinyl H), 2.22 (s, 3H, triazolyl CH
3
). ). C-NMR (DMSO-d
66.23, 156.25, 155.35, 153.74, 153.47, 147.96, 135.40, 133.30, 123.19, 119.76,
15.78, 114.26, 113.40, 106.81, 106.65, 70.85, 51.66, 50.54, 50.17, 47.10, 44.14,
6
): δ
1
1
2
7

ACCEPTED MANUSCRIPT
-
1
1
1
5
0.36. IR (KBr pellet, cm ): ν 3429, 2925, 2855, 1751, 1655, 1519, 1449, 1350,
+
291, 1235, 1136, 1108, 1037. MS 556.2 (M ). Anal calcd for C24
1.80, H: 4.53, N: 20.14 found C: 51.72, H: 4.29, N: 19.89.
8 7
H25FN O : C:
5
.2.3.21. (R)-N-(2-(4-(4-(5-((1H-1,2,3-Triazol-1-yl)methyl)-2-oxooxazolidin-3-yl)-2-
fluorophenyl)piperazin-1-yl)-2-oxoethyl)thiophene-2-sulfonamide (6w)
Compound 6w was prepared via the general procedure from 15 (500 mg, 0.97 mmol)
2
-thiophenesulfonyl chloride (529 mg, 2.89 mmol), in TEA and CH
3
CN (10 ml) to
give a crude solid. Recrystallized (CH CN) gave the title compound as brown crystals
3
o
1
(
320 mg, yield 60%), mp- 195-197 C. H-NMR (DMSO-d , 600 MH ): δ 8.16 (s, 1H,
6 Z
2
triazolyl H), 7.93 (br., 1H, NH, exchangeable with D O, overlaps partly with
thipohene H), 7.92 (dd, 1H, J=1.1 Hz, 4.9 Hz, thiophene H), 7.76 (s, 1H, triazolyl H),
.64 (dd, 1H, J=1.2 Hz, 3.7 Hz, thiophene H), 7.41 (dd, 1H, J=2.4 Hz, 14.7 Hz,
7
phenyl H), 7.18 (dd, 1H, J=3.9 H , 4.8 Hz, thiophene H), 7.13 (dd, 1H, J=2.2 Hz, 8.8
Z
Hz, phenyl H), 7.04 (t, 1H, J=9.3 Hz, phenyl H), 5.10-5.14 (m,1H, oxazolidinone H),
4
.82 (d, 2H, J=5.1 Hz, CH
oxazolidinone H, CH ), 3.51-3.54 (m, 4H, piperazinyl H), 2.91 (br. d, 4H, piperazinyl
H). ). C-NMR (DMSO-d ): δ 164.38, 154.20, 152.58, 139.92, 134.24, 132.10,
31.34, 130.65, 126.47, 124.71, 118.61, 113.14, 106.82, 69.53, 50.56, 49.19, 48.92,
2
), 4.20 (t, 1H, J=9.2 Hz, oxazolidinone H), 3.86 (m, 3H,
2
1
3
6
1
4
1
-1
5.94, 43.10, 41.43. IR (KBr pellet, cm ): ν 3437, 2912, 1743, 1642, 1520, 1484,
+
412, 1396, 1346, 1286, 1226, 1158, 1109, 1031. MS 549.2 (M ). Anal calcd for
22 7 5 2
C H24FN O S : C: 48.08, H: 4.40, N: 17.84; found C: 48.01, H: 4.31, N: 17.70.
5
.2.3.22. (R)-N-(2-(4-(2-Fluoro-4-(5-((4-methyl-1H-1,2,3-triazol-1-yl)methyl)-2-oxo-
oxazolidin -3-yl)phenyl)piperazin-1-yl)-2-oxoethyl)thiophene-2-sulfonamide (6x)
2
8