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Article

Heterocycles [h]Fused onto 4-Oxoquinoline-3-Carboxylic Acid, Part IV. Convenient Synthesis of Substituted Hexahydro [1,4]Thiazepino[2,3-h]quinoline-9-carboxylic Acid and Its Tetrahydroquino[7,8-b]benzothiazepine Homolog

by
Mohammed H. Al-Huniti
1,
Mustafa M. El-Abadelah
1,
Jalal A. Zahra
1,*,
Salim S. Sabri
2 and
Arnd Ingendoh
3
1
Chemistry Department, Faculty of Science, The University of Jordan, Amman 11942, Jordan
2
University of Sharjah, Sharjah, P. O. Box 27272, United Arab Emirates (UAE)
3
Bruker Daltonik GmbH, Fahrenheitstr. 4, D-28359 Bremen, Germany
*
Author to whom correspondence should be addressed.
Molecules 2007, 12(8), 1558-1568; https://doi.org/10.3390/12081558
Submission received: 4 June 2007 / Revised: 19 July 2007 / Accepted: 19 July 2007 / Published: 27 July 2007
Browse Figures
Versions Notes

Abstract

:
Substituted [1,4]thiazepino[2,3-h]quinolinecarboxylic acid 3 is prepared by PPA-catalyzed thermal lactamization of the respective 8-amino-7-[(2-carboxyethyl)thio]-1,4-dihydroquinoline-3-carboxylic acid 9. The latter synthon is obtained by reduction of the 8-nitro-1,4-dihydroquinoline precursor 8 which, in turn, is made accessible via interaction of 3-mercaptopropionic acid with 7-chloro-1-cyclopropyl-6-fluoro-8-nitro-1,4-dihydroquinoline-3-carboxylic acid 7 in the presence of triethylamine. A benzo-homolog of 3, namely tetrahydroquino[7,8-b]benzothiazepine-3-carboxylic acid 6, is analogously prepared via the raction of 2-mercaptobenzoic acid with 7, followed by reduction of the resulting 7-[(2-carboxyphenyl)thio]-8-nitro product 10 into the corresponding 8-amino derivative 11, and subsequent lactamization. The structures assigned to 3, 6 and 8-11 are based on microanalytical and spectral (IR, MS, NMR) data.

Introduction

Synthetic fluoroquinolones (e.g. ciprofloxacin (1a) [2]) represent a successful achievement towards the design and development of potent antiinfectious drugs [2,3], while some related derivatives, such as 1b [4], exhibit antitumor activity[4,5,6]. On the other hand, 2,3-dihyro-1,5-benzothiazpin-4(5H)-one (2a) and several derivatives thereof, e.g diltiazem [7] (2b, Figure 1), are of considerable interest both synthetically [8] and pharmacologically [9,10,11,12,13]. Depending on the nature of substituents at C-2, C-3 and N-5 of the parent skeleton (ring C, Figure 1), such derivatives exhibit coronary vasodilator [9], calcium antagonist [10], antidepressant [11], anticonvulsant [12] or antimicrobial [13] activities.
Molecules 12 01558 g001 550
Figure 1. Structures of 4-oxoquinolines 1a, 1b, dihydro-1,5-benzothiazepin-4(5H)-ones 2a, 2b and 2,8-dioxo-hexahydro[1,4]thiazepino[2,3-h]quinoline 3.
Figure 1. Structures of 4-oxoquinolines 1a, 1b, dihydro-1,5-benzothiazepin-4(5H)-ones 2a, 2b and 2,8-dioxo-hexahydro[1,4]thiazepino[2,3-h]quinoline 3.
Molecules 12 01558 g001
Several dibenzo[b,f][1,4]thiazepin-11(10H)-ones (e.g. 4, Figure 2) were also prepared [14,15,16,17], some of which were reported to exhibit activity against the HIV virus [15] or useful agents for the prevention and treatment of AIDS [16], while others act as leukotriene antagonists [17]. Compounds of type 4 have been readily transformed into 11-piperazinyldibenzo[b,f][1,4]thiazepines, exemplified by 11-{4-[2-(2-Hydroxyethoxy)-ethyl]piperazinyl}dibenzo[b,f][1,4]thiazepine, commonly known as quetiapine [18] (5, Figure 2).
The latter compound and its congeners are useful agents for treating anxiety [19] and substance-related disorders [20], act as calcium channel antagonists [21], neuroleptic and antipsychotic agents [22], and display antidopaminergic activity [23].
Herein, we wish to report on the synthesis of new heterocyclic ring systems incorporating a 4-oxopyridine entity condensed either to 1,5-benzothiazepinone (compound 3, Figure 1), or to dibenzo [b,f][1,4]thiazepinone (compound 6, Figure 2) as depicted in Scheme 1 and Scheme 2, respectively. The tricyclic system 3 encompasses the structural features both of fluoroquinolone (rings A, B) and 1,5-benzothiazepinone (rings B, C), while the tetracyclic assembly 6 incorporates fluoroquinolone (rings A, B) and dibenzo[1,4]thiazepinone (rings B, C, D) chemotypes. Such new hybrid heterocyclics might display interesting bioproperties.
Molecules 12 01558 g002 550
Figure 2. Structures of dibenzo[b,f][1,4]thiazepine-11(10H)-ones 4, quetiapine 5 and tetrahydroquino[7,8-b][1,4]benzothiazepine 6.
Figure 2. Structures of dibenzo[b,f][1,4]thiazepine-11(10H)-ones 4, quetiapine 5 and tetrahydroquino[7,8-b][1,4]benzothiazepine 6.
Molecules 12 01558 g002

Results and Discussion

Direct interaction between 7-chloro-1-cyclopropyl-6-fluoro-8-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (7) [24,25] and 3-mercaptopropionic acid, in aqueous acetone containing triethylamine, produced the corresponding 7-[(2-carboxyethyl)thio]-8-nitro-1,4-dihydroquinoline derivative (8) (Scheme 1).
Molecules 12 01558 g003 550
Scheme 1. Synthesis of hexahydro[1,4]thiazepino[2,3-h]quinoline-9-carboxylic acid 3.
Scheme 1. Synthesis of hexahydro[1,4]thiazepino[2,3-h]quinoline-9-carboxylic acid 3.
Molecules 12 01558 g003
Herein, 3-mercaptopropionic acid acts as 'sulfur' nucleophile that displaces the C(7)- chlorine atom in the substrate (7). This reaction follows a nucleophilc aromatic substitution 'SN-Ar' (addition –elimination) path, and is facilitated by the presence of the electron withdrawing C(6)-fluoro, C(4)-keto, and C(8)-nitro groups. Reduction of the latter 8-nitro compound 8 with sodium dithionite in aqueous potassium carbonate gives the respective 8-amino derivative 9. In a separate step, compound 9 underwent lactamization upon heating with polyphosphoric acid (PPA) to afford a tricyclic system, namely 2,8-dioxohexahydro[1,4]thiazepino[2,3-h]quinoline-3-carboxylic acid (3). Likewise, the reaction of 2-mercaptobenzoic acid with 7 provided the corresponding 7-[(2-carboxyphenyl)thio]-8-nitro-1,4-dihydroquinoline derivative 10 which was then reduced to the respective 7-amino-1,4-dihydroquinoline-3-carboxylic acid 11 (Scheme 2). Subsequent lactamization of 11, using PPA, afforded the target tetracyclic product, namely 4,12-dioxotetrahydroquino[7,8-b]benzothiazepine-3-carboxylic acid (6). The elemental analyses and spectral (IR, MS, NMR) data of 3, 6 and 8-11, given in the Experimental part, are in conformity with the suggested structures. Thus, their MS spectra display the correct molecular ion peaks for which the measured HRMS data are in good agreement with the values calculated for the molecular formulae. Assignments of the 1H- and 13C- signals to the different respective protons and carbons are based on DEPT and 2D (COSY, HMQC, HMBC) experiments which showed correlations consistent with these assignments.
Molecules 12 01558 g004 550
Scheme 2. Synthesis of tetrahydroquino[7,8-b]benzothiazepine-3-carboxylic acid 6.
Scheme 2. Synthesis of tetrahydroquino[7,8-b]benzothiazepine-3-carboxylic acid 6.
Molecules 12 01558 g004
For compound 3, distinct ''three-bond'' (1H, 13C)–correlations are observed between H-10 and each of CO2H, C-8, C-11a and C-1', as well as between H-7 and each of C-8, C-11a and C-5a, and between H-1' and each of C-10 and C-11a. Corresponding long-range correlations are also observed for compounds 6 and 8-11 between H-2, H-5, H-1' and their neighbor carbons. The skeletal carbons of benzo-fused entity (ring B) in 3, 6 and 8-11 are recognizable by their doublet signals originating from scalar (through bond) coupling with the neighboring fluorine atom. Also, the C-3'' methylene carbon in 8 appears as a doublet due to through-space (dipolar) coupling with the nearby fluorine atom.

Experimental

General

Ethyl 3-(N,N-dimethylamino)acrylate, 2,4-dichloro-5-fluoro-3-nitrobenzoic acid and cyclopropyl-amine were purchased from Acros. 3-Mercaptopropionic acid and 2-mercaptobenzoic acid were purchased from Aldrich. Melting points were determined on a Gallenkamp capillary melting point apparatus and are uncorrected. 1H- (300 MHz), 13C-NMR (75 MHz) and DEPT spectra, and 2D (H-H COSY, HMQC, HMBC) experiments were measured on a Bruker DPX-300 instrument with Me4Si as internal reference and DMSO-d6 as solvent. High resolution mass spectra (HRMS) were measured in positive ion mode by Electrospray (ESI) on Bruker APEX-Qe 94 instrument. The samples were dissolved in acetonitrile, diluted in spray solution (methanol/water 1:1 v/v + 0.1% formic acid) and infused using a syringe pump with a flow rate of 2 µL/min. External calibration was conducted using the arginine cluster in a mass range m/z 175-871. Electron-impact mass spectra (EIMS) were obtained using a Varian MAT-212 spectrometer at 70 eV and at ion source temperature of 200 oC. IR spectra were recorded as KBr discs on a Nicolet Impact-400 FT-IR spectrophotometer. Elemental analyses were preformed at the Microanalytical Laboratory of the Hashemite University, Zarqa, Jordan.

7-Chloro-1-cyclopropyl-6-fluoro-8-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid(7)

This compound [mp 256-257oC (decomp); Lit. [25] 261oC (decomp)] was prepared according to literature methods [24] by acid-catalyzed hydrolysis of the corresponding ethyl ester, in turn prepared from 2,4-dichloro-5-fluoro-3-nitrobenzoic acid, ethyl 3-(N,N-dimethylamino)acrylate and cyclopropyl- amine by following the stepwise synthetic procedures as reported for the corresponding methyl ester analog [mp 175-176 oC (decomp); Lit. [24] 174-176 oC (decomp)] [25,26].

7-[(2-Carboxyethyl)thio]-1-cyclopropyl-6-fluoro-8-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (8)

3-Mercaptopropionic acid (0.18 g, 1.7 mmol) was added to a stirred solution of 7 (0.5 g, 1.5 mmol) in aqueous acetone (45 mL, 1:2 v / v) and Et3N (6 mL) at room temperature (rt) and kept in the dark for 7 h. Thereafter, the reaction mixture was washed with CHCl3 (2 x 10 mL), the aqueous layer was separated and acidified with 3N HCl. The resulting yellow precipitate was collected and recrystallized from CHCl3. Yield 0.54 g (91%); mp 205-207oC; IR (cm-1) 3500, 3430, 3080, 2914, 2742, 1720, 1679, 1564, 1532, 1481, 1430, 1347, 1329, 1259; 1H-NMR δ 1.00/1.10 (2 m, 4H, 2H-2'/2H-3'), 2.45 (t, J = 6.7 Hz, 2H, H-2''), 3.20 (t, J = 6.7 Hz, 2H, H-3''), 3.70 (m, 1H, H-1'), 8.29 (d, 3JH-F = 9 Hz, 1H, H-5), 8.78 (s, 1H, H-2), 13.05 (br s, 2H, 2CO2H); 13C-NMR δ 11.1 (C-2'/C-3'), 30.5 (d, JC-F = 7.3 Hz, C-3''), 34.9 (C-2''), 39.6 (C-1'), 109.2 (C-3), 114.4 (d, 2JC-F = 25.6 Hz, C-5), 126.9 (d, 2JC-F = 24.7 Hz, C-7), 129.0 (d, 3JC-F = 7.9 Hz, C-4a), 131.3 (d, 4JC-F = 2.6 Hz, C-8a), 144.9 (d, 3JC-F = 1.5 Hz, C-8), 153.3 (C-2), 158.5 (d, 1JC-F = 248 Hz, C-6), 164.9 [C(3)CO2H], 172.7 [C(2'')CO2H], 175.6 (d, 4JC-F = 2.3 Hz, C-4). EIMS m/z (%): 396 (M+, 6), 378 (9), 352 (64), 334 (56), 307 (29), 269 (43), 263 (68), 233 (52), 200 (47), 191 (71), 172 (35), 108 (15), 55 (100); HRMS (EI): Calcd. for C16H13FN2O7S 396.04271; found 396.03918; Anal. calcd. for C16H13FN2O7S (396.35):C, 48.49; H, 3.31; N, 7.07; S, 8.09. Found: C, 48.26; H, 3.24; N, 7.16; S, 7.93.

8-Amino-7-[(2-carboxyethyl)thio]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (9)

A solution of sodium dithionite (0.87 g, 5 mmol) in water (5 mL) was added dropwise at rt to a stirred solution of 8 (0.4 g, 1.0 mmol) in water (20 mL) containing K2CO3 (0.96 g, 7 mmol). The reaction mixture was stirred at rt for an additional 8 h and then extracted with CHCl3 (2 X 10 mL). The aqueous layer was then acidified with 6N HCl, whereby the title compound was obtained as a pale yellow precipitate which was collected and recrystallized from CHCl3/MeOH. Yield 0.3 g (81%); mp 216-218oC; IR (cm-1) 3498, 3343, 3080, 3919, 1730, 3919, 1730, 1595, 1582, 1530, 1492, 1447, 1337, 1254, 1170; 1H-NMR δ 1.04, 1.16 (2 m, 4H, 2H-2' / 2H-3'), 2.44 (t, J = 7 Hz, 2H, 2H-2''), 2.93 (t, J = 7 Hz, 2H, 2H-3''), 4.53 (m, 1H, H-1'), 6.51 (br s, 2H, NH2), 7.20 (d, 3JH-F = 8.4 Hz, 1H, H-5), 8.72 (s, 1H, H-2), 14.70 (br s, 2H, 2CO2H); 13C-NMR δ 10.6 (C-2'/C-3'), 29.4 (C-3''), 34.6 (C-2''), 39.9 (C-1'), 97.0 (d, 2JC-F = 27.1 Hz, C-5), 107.2 (C-3), 109.9 (d, 2JC-F = 23.4 Hz, C-7), 126.9 (d, 4JC-F = 1 Hz, C-8a), 129.2 (d, 3JC-F = 9.8 Hz, C-4a), 145.2 (d, 3JC-F = 3.3 Hz, C-8), 151.5 (C-2), 161.4 (d, 1JC-F = 240 Hz, C-6), 166.0 [C(3)CO2H), 173.1 [ C(2″)-CO2H], 177.2 (d, 4JC-F = 2 Hz, C-4); HRMS(ESI): calcd for C16H16FN2O5S+ [M+H]+ : 367.07640, found: 367.07568; Anal. calcd. for C16H15FN2O5S (366.36):C, 52.45; H, 4.13; N, 7.65; S, 8.75. Found: C, 52.31; H, 4.08; N, 7.55; S, 8.48.

11-Cyclopropyl-6-fluoro-2,8-dioxo-1,2,3,4,8,11-hexahydro[1,4]thiazepino[2,3-h]quinoline-9-carboxylic acid (3)

Compound 9 (0.2 g, 0.55 mmol) was suspended in polyphosphoric acid (PPA, 7 g) and heated at 145-150 °C for 2h. The reaction mixture was then poured into water (30 mL) and stirred for 20 min. The resulting white precipitate was collected and recrystalised from CHCl3/MeOH. Yield 0.13g (68%); mp 307-309 oC; IR (cm-1) 3427, 3286, 3080, 2932, 1717, 1595, 1530, 1498, 1460, 1408, 1389, 1312, 1254, 1228, 1183; 1H-NMR δ 1.03 (m, 4H, 2H-2' / H-3'), 2.74 (t, J = 7 Hz, 2H, 2H-4), 3.53 (t, J = 7 Hz, 2H, 2H-3), 4.29 (m, 1H, H-1'), 7.94 (d, 3JH-F = 8.1 Hz, 1H, H-7), 8.79 (s, 1H, H-10), 10.02 (br s, 1H, N(1)H), 13.42 (br s, 1H, CO2H); 13C-NMR δ 9.5 ( C-2'/C-3'), 33.2 (C-4), 34.6 (C-3), 41.0 (C-1'), 108.2 (C-9), 108.6 (d, 3JC-F = 26.1 Hz, C-7), 126.6 (d, 2JC-F = 20.7 Hz, C-5a), 128.6 (d, 3JC-F = 8.6 Hz, C-7a), 133.7 (d, 3JC-F = 2.2 Hz, C-11a), 135.9 (d, 3JC-F = 1.6 Hz, C-11b), 152.5 (C-10), 159.6 (d, 1JC-F = 244 Hz, C-6), 165.5 (C(9)-CO2H), 172.0 (C-2), 176.8 (d, 4JC-F = 3 Hz, C-8); EIMS m/z (%): 348(M+, 27), 320(5), 276(15), 247(15), 233(12), 220(20), 193(8), 118(6), 152(4), 135(14), 108(9), 55(100); HRMS (ESI): calcd for C16H14FN2O4S+ [M+H]+: 349.06583. Anal. calcd. for C16H13FN2O4S (348.35):C, 55.17; H, 3.76; N, 8.04; S, 9.20. Found: C, 55.86; H, 3.74; N, 7.91; S, 9.27.

7-[(2-Carboxyphenyl)thio]-1-cyclopropyl -6-fluoro-8-nitro-4-oxo-1,4-dihydroquinolin-3-carboxylic acid (10)

Prepared from 2-mercaptobenzoic acid (0.26 g, 1.7 mmol) and 7 (0.5 g, 1.5 mmol) using the procedure and experimental conditions described above in the preparation of 8. The title compound was obtained as a white precipitate which was collected and recrystallized from chloroform/petroleum ether. Yield 0.62 g (93 %); mp 279-281oC. IR (cm-1) 3395, 3067, 2971, 2932, 2669, 2605, 1692, 1605, 1542, 1351, 1459, 1419, 1339, 1328, 1288, 1115; 1H-NMR δ 1.02, 1.18 (2 m, 4H, 2H-2' / 2H-3'), 3.74 (m, 1H, H-1'), 6.80 (dd, J = 7.9, 1.0 Hz, 1H, H-6''), 7.30 (ddd, J = 7.3, 7.5, 1 Hz, 1H, H-4''), 7.38 (ddd, J = 7.9, 7.3, 1.6 Hz, 1H, H-5''), 7.97 (dd, J = 7.5, 1.6 Hz,1H, H-3''), 8.33 (d, 3JH-F = 8 Hz, 1H, H-5), 8.82 (s, 1H, H-2), 13.75 (br s, 2H, 2CO2H); 13C-NMR δ 11.2 (C-2'/C-3'), 39.6 (C-1'), 109.4 (C-3), 115.0 (d, 2JC-F = 25.6 Hz, C-5), 124.3 (d, 2JC-F = 25.7 Hz, C-7), 126.9 (C-4''), 127.4 (C-6''), 128.5 (C-2''), 130.9 (d, 3JC-F = 7.8 Hz, C-4a), 131.6 (d, 3JC-F = 2.6 Hz, H-8a), 131.7 (C-3''), 133.7 (C-5''), 137.6 (C-1''), 146.3 (C-8), 153.3 (C-2), 155.1 (d, 1JC-F = 262 Hz, C-6), 165.0 [C(3)-CO2H], 168.1 [C(2″)-CO2H], 175.6 (d, 4JC-F = 2.2 Hz, C-4); HRMS (ESI): calcd. for C20H14FN2O7S+[M+H]+ : 445.05058 , found: 445.04989; Anal. calcd. for C20H13FN2O7S (444.39):C, 54.05; H, 2.95; N, 6.30; S, 7.22. Found: C, 54.23; H, 3.04; N, 6.18; S, 7.01.

8-Amino-7-[(2-carboxyphenyl)thio]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (11)

A solution of sodium dithionite (0.52 g, 3.0 mmol) in water (5 mL) was added dropwise to a stirred solution of 10 (0.4 g, 0.9 mmol) in water (10 mL) containing dissolved K2CO3 (0.56 g. 4.0 mmol) at rt. Thereafter, the reaction mixture was stirred at rt for 5 h and then washed with CHCl3 (2 X 8 mL). The aqueous layer was neutralized with 6N HCl, the precipitated product was collected, dried, and recrystallized from CHCl3. Yield = 0.29 g (77%); mp 312-313 oC; IR (cm-1) 3491, 3379, 3086, 2771, 2610, 1704, 1678, 1582, 1524, 1453, 1350, 1235, 1138; 1H-NMR δ 1.09 (m, 4H, 2H-2'/2H-3'), 4.51 (m, 1H, H-1'), 6.49 (br s, 2H, NH2), 6.66 (d, J = 7.9 Hz, 1H, H-6''), 7.22 (dd, J = 6.8, 7.2 Hz, 1H, H-4''), 7.29 (d, 3JH-F = 8.3 Hz, 1H, H-5), 7.34 (dd, J = 7.9, 7.2 Hz, 1H, H-5''), 7.97 (d, J = 6.8 Hz, 1H, H-3''), 8.76 (s, 1H, H-2), 13.40 [br s, 1H, C(2'')-CO2H], 14.80 [br s, 1H, C(3)-CO2H]; 13C-NMR δ 10.6 (C-2'/C-3'), 39.8 ( C-1'), 97.2 (d, 2JC-F = 27.1 Hz, C-5), 107.5 (C-3), 107.6 (d, 2JC-F = 23.2 Hz, C-7), 125.2 (C-6''), 125.6 (C-4''), 127.3 (C-8a), 128.7 (C-2''), 130.3 (d, 3JC-F = 10.3 Hz, C-4a), 132.0 (C-3''), 133.2 (C-5''), 138.3 (C-1''), 146.0 (d, 3JC-F = 3 Hz, C-8), 151.7 (C-2), 161.4 (d, 1JC-F = 242 Hz, C-6), 166.0 [C(3)-CO2H], 168.1 [C(2'')-CO2H], 177.2 (d, 4JC-F = 3 Hz, C-4); EIMS m/z (%): 414 (M+, 8), 396 (10), 370 (64), 352 (82), 323 (100), 295 (31), 217 (46), 189 (59), 154 (19), 136 (50), 108 (11); HRMS (EI): calcd. for C20H15FN2O5S: 414.06854; found: 414.07027; Anal. calcd. for C20H15FN2O5S (414.41): C, 57.97; H, 3.65; N, 6.76; S, 7.74. Found: C, 57.68; H, 3.54; N, 6.72; S, 7.88.

1-cyclopropyl-6-fluoro-4,12-dioxo-1,4,12,13-tetrahydroquino[7,8-b]benzothiazepine-3-carboxylic acid (6)

Prepared from compound 11 (0.2 g, 0.48 mmol) by heating in PPA (7 g) at 145-150 °C for 2h. Work-up of the reaction mixture, as described for the preparation of 3, produced a brown precipitate which was collected, washed with cold EtOH (1 mL) and dried. Yield 0.14 g (74 %) mp 317-319 °C (decomp); IR (cm-1) 3433, 3247, 3086, 2929, 1713, 1674, 1614, 1349, 1490, 1466, 1425, 1383, 1330, 1259, 1235, 1193; 1H-NMR δ 0.36 , 1.06 (2m, 2H) and 0.91, 1.30 (2m, 2H) (2H-2' / 2H-3'), 4.37 (m, 1H, H-1'), 7.53 (m, 2H, H-9 + H-10), 7.62 (dd, J = 7.1, 1.4 Hz, 1H, H-8), 7.81 (dd, J = 7.3, 1.5 Hz, 1H, H-11), 7.90 (d, 3JH-F = 8.0 Hz, 1H, H-5), 8.80 (s, 1H, H-2), 10.99 (br s, 1H, N(1)-H), 13.30 (br s, 1H, CO2H); 13C-NMR δ 7.6, 11.9 ( C-2' /C-3'), 40.9 (C-1'), 108.3 (d, 2JC-F = 26 Hz, C-5), 108.5 (C-3), 128.7 (d, 3JC-F = 8.2 Hz, C-4a), 130.7 (C-9), 132.0 (C-11), 132.4 (d, 2JC-F = 22.4 Hz, C-6a), 132.6 (d, 4JC-F = 1.7 Hz, C-13a), 132.9 (C-10), 133.0 (C-8), 134.2 (d, 4JC-F = 1.9 Hz, C-13b), 135.3 (C-11a), 138.3 (C-7a), 152.6 (C-2), 157.3 (d, 1JC-F = 245 Hz, C-6), 165.5 (CO2H), 168.4 (C-12), 176.8 (d, 4JC-F = 2.9 Hz, C-4); EIMS m/z (%): 396 (M+, 43), 378 (5), 352 (100),337 (6), 323 (19), 319 (46), 295 (16), 269 (10), 241 (9), 214 (11), 196 (6), 168 (5), 157 (4), 107 (11); HRMS (ESI): calcd. for C20H14FN2O4S+ [M+H]+: 397.06583, found:397.06535; Anal. calcd. for C20H13FN2O4S (396.36): C, 60.60; H, 3.31; N, 7.07; S, 8.09. Found: C, 60.48; H, 3.23; N, 7.02; S, 7.87.

Acknowledgements

We wish to thank the Deanship of Scientific Research-The University of Jordan, Amman-Jordan for financial support.

References and Notes

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Al-Huniti, M.H.; El-Abadelah, M.M.; Zahra, J.A.; Sabri, S.S.; Ingendoh, A. Heterocycles [h]Fused onto 4-Oxoquinoline-3-Carboxylic Acid, Part IV. Convenient Synthesis of Substituted Hexahydro [1,4]Thiazepino[2,3-h]quinoline-9-carboxylic Acid and Its Tetrahydroquino[7,8-b]benzothiazepine Homolog. Molecules 2007, 12, 1558-1568. https://doi.org/10.3390/12081558

AMA Style

Al-Huniti MH, El-Abadelah MM, Zahra JA, Sabri SS, Ingendoh A. Heterocycles [h]Fused onto 4-Oxoquinoline-3-Carboxylic Acid, Part IV. Convenient Synthesis of Substituted Hexahydro [1,4]Thiazepino[2,3-h]quinoline-9-carboxylic Acid and Its Tetrahydroquino[7,8-b]benzothiazepine Homolog. Molecules. 2007; 12(8):1558-1568. https://doi.org/10.3390/12081558

Chicago/Turabian Style

Al-Huniti, Mohammed H., Mustafa M. El-Abadelah, Jalal A. Zahra, Salim S. Sabri, and Arnd Ingendoh. 2007. "Heterocycles [h]Fused onto 4-Oxoquinoline-3-Carboxylic Acid, Part IV. Convenient Synthesis of Substituted Hexahydro [1,4]Thiazepino[2,3-h]quinoline-9-carboxylic Acid and Its Tetrahydroquino[7,8-b]benzothiazepine Homolog" Molecules 12, no. 8: 1558-1568. https://doi.org/10.3390/12081558

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