3.1. Chemistry
Melting points were obtained on a Barnstead 9001 Electrothermal melting point apparatus (Chula Vista, CA, USA) and are uncorrected. IR spectra were recorded on a Perkin Elmer FT-IR Spectrum BX Spectrometer (Waltham, MA, USA) at cm−1 scale using KBr discs. 1H NMR and 13C NMR were recorded on a JEOL 300 MHz Spectrometer (Tokyo, Japan), Japan and chemical shift values were expressed in δ values (ppm) relative to tetramethylsilane (TMS) as internal standard. Coupling constants are given in Hz. The mass spectra were recorded on GCMC-QP 1000 EX Shimadzu Gas Chromatography MS spectrometer (Kyoto, Japan), Japan E.I.70 ev. Elemental analysis (C, H, N) were carried out at the Micro analytical Center, Faculty of Science, Cairo University, Cairo, Egypt, and were in full agreement with the proposed molecular weights within ± (0.2%–0.3%) of the theoretical values. All reagents were of commercial quality and were used without further purification. Organic solvents were dried in the presence of an appropriate drying agent and were stored over suitable molecular sieves. Reaction progress was monitored by analytical thin layer chromatography (TLC) on precoated (0.75 mm) silica gel GF254 plates and the products were visualized by UV light.
3.1.1. N-2-Chloroacyl-4-[5-(p-tolyl)-3-trifluoromethyl-1H-pyrazol-1-yl] benzene sulfonamide (2a)
According to Reported Method [
19].
N-(2- or 4-Chloroalkyl)-4-[5-(
p-tolyl)-3-trifluoromethyl-1
H-pyrazol-1-yl] Benzene Sulfonamide (
2b,
c). A mixture of celecoxib
1 (0.01 mol) and 1,2-chloropropionyl chloride, or chlorobutyryl chloride (0.04 mol) was heated under reflux for 1 h, the mixture was concentrated by evaporation under vacuum, after cooling the reaction mixture was poured onto ice cold water and the solid formed was filtered off, dried and recrystallized from ethanol to give the compounds
2b,
c respectively.
3.1.2. N-(2-Chloropropionyl)-4-[5-(p-tolyl)-3-trifluoromethyl-1H-pyrazol-1-yl] benzene sulfonamide (2b)
Yield 82%; m.p.: 144–146 °C; IR (νmax/cm−1): 3232 (NH), 1732 (C=O); 1H NMR (DMSO-d6) δ: 1.40 (d, J = 6.5 Hz, 3H, CH3), 2.20 (s, 3H, Ar–CH3), 4.40 (q, 1H, CH–Cl), 6.67 (s, 1H, pyrazole-H), 7.19–7.95 (m, 9H, Ar–H + NH); 13C NMR (DMSO-d6) δ: 20.6 (CH3), 21.3 (Ar–CH3), 56.5 (Cl–CH), 106.1, 125.3, 125.9, 126.7, 128.7, 129.3, 139.0, 141.0, 142.6, 143.9, 145.2, 154.5 (CF3, Ar–C and C=N), 175.2 (C=O); MS: m/z (%): 471, 473 (M+, M+2, 28.8, 11.2)
3.1.3. N-(4-Chlorobutyryl)-4-[5-(p-tolyl)-3-trifluoromethyl-1H-pyrazol-1-yl] benzene sulfonamide (2c)
Yield 75%; m.p.: 135 °C; IR (νmax/cm−1): 3244 (NH), 1735 (C=O); 1H NMR (DMSO-d6) δ: 2.0 (m, 2H, CH2–CH2–CH2), 2.3 (s, 3H, Ar–CH3), 2.39 (t, J = 7.5 Hz, 2H, COCH2), 3.8 (t, J = 7.5 Hz, 2H, CH2Cl), 6.67 (s, 1H, pyrazole–H), 7.0 (d, J = 8 Hz, 2H, H-3, 5 p-tolyl), 7.1 (d, J = 8 Hz, 2H, H-2, 6 p-tolyl), 7.4 (d, J = 9 Hz, 2H, H-2, 6 benzene sulfonamide), 7.9 (d, J = 9 Hz, 2H, H-3, 5 benzene sulfonamide); 13C NMR (DMSO-d6) δ: 18.2 (CH2–CH2–CH2), 22.9 (CH3), 30.3 (CH2CO), 47.3 (CH2Cl), 106.4, 125.3, 125.6, 128.7, 129.1, 129.8, 130.8, 137.2, 139.9, 143.6, 145.3, 154.5 (CF3, Ar–C and C=N), 173.2 (C=O); MS: m/z (%): 485, 487 (M+, M+2, 37.8, 13.2).
3.1.4. General Method for Preparation of N-(2- or 4-(9,10-Dihydro-9,10-dioxoanthracen-2-yl) aminoacyl) 4-[5-(p-tolyl)-3-trifluoromethyl-1H-pyrazol-1-yl] benzene sulfonamide (3a–c)
To a solution of 2a–c (0.01 mol) in ethanol (15 mL), 2-aminoanthraquinone 8 (0.01 mol) in DMF (3 mL) was added. The mixture was then heated to reflux for 4–5 h, the excess solvent was removed under vacuum and after cooling the precipitate formed was collected by filtration, washed with water and recrystallized from the proper solvent to obtain 3a–c, respectively.
3.1.5. N-(2-(9,10-Dihydro-9,10-dioxoanthracen-2-yl) aminoacetyl)-4-[5-(p-tolyl)-3-trifluoromethyl-1H-pyrazol-1-yl] benzene sulfonamide (3a)
Yield 70%; Crystallized from ethanol; m.p.: 156–158 °C; IR (νmax/cm−1): 3345, 3234 (2NH), 1673 (br., 3C=O); 1H NMR (DMSO-d6) δ: 2.30 (s, 3H, Ar–CH3), 4.30 (s, 2H, N–CH2), 6.67 (s, 1H, pyrazole–H), 7.0–7.1 (d, d, J = 8 Hz, 2H, H-3, 4 anthraquione), 7.36 (s, 1H, H-1, anthra quinone), 7.4 (d, J = 8.5 Hz, 2H, H-3, 5 p-tolyl), 7.6–8.1 (m, 10 H, Ar–H), 8.9 (br. s, 2H, 2NH); 13C NMR (DMSO-d6) δ: 21.3 (Ar–CH3), 29.7 (CH2), 106.3, 109.6, 118.0, 121.0, 126.1, 126.3, 126.4, 126.7, 128.7, 128.9, 129.60, 133.0, 133.3, 133.7, 134.3, 134.9, 137.6, 139.2, 142.3, 154.7 (CF3, Ar–C and C=N), 173.9, 180.1, 183.3 (3C=O); MS: m/z (%): 644 (M+, 14.7).
3.1.6. N-(2-(9,10-Dihydro-9,10-dioxoanthracen-2-yl)-aminopropionyl)-4-[5-(p-tolyl)-3-trifluoromethyl-1H pyrazol-1-yl] benzene sulfonamide (3b)
Yield 75%; Recrystallized from dil. ethanol; m.p.: 261–263 °C; IR (νmax/cm−1): 3361, 3228 (2NH), 1672, 1628 (3C=O); 1H NMR (DMSO-d6) δ: 1.4 (d, J = 6.5 Hz, 3H, CH–CH3), 2.2 (s, 3H, Ar–CH3), 3.9 (q, 1H, CH–CH3), 6.67 (s, 1H, pyrazole-H), 7.0–7.1 (d, d, J = 8 Hz, 2H, H-3, 4 anthraquinone), 7.3 (d, J = 8 Hz, 5, 2H, H-3, 5 p-tolyl), 7.4–8.1 (m, 11 H, Ar–H), 10.9 (br. s, 2H, 2-NH); 13C NMR (DMSO-d6) δ: 17.6 (CH3), 21.3 (Ar–CH3), 59.5 (NH–CH), 109.2, 109.6, 110.2, 116.5, 118.0, 121.1, 126.3, 126.9, 129.5, 133.0, 133.3, 133.7, 134.3, 134.9, 139.8, 141.3, 142.5, 144.6, 145.2, 154.7 (CF3, Ar–C and C=N), 175.2, 180.0, 183.3 (3C=O); MS: m/z (%): 658 (M+, 12.9).
3.1.7. N-(4-(9,10-Dihydro-9,10-dioxoanthracen-2-yl-aminobutanoyl)-4-[5-(p-tolyl)-3-trifluoromethyl-1H-pyrazol-1-yl] benzene sulfonamide (3c)
Yield: 82%, Recrystallized from CHCl3; m.p.: 214–216 °C, IR (νmax/cm−1): 3359, 3227 (2NH), 1672 (br, 3C=O), 1H NMR (DMSO-d6) δ: 1.20 (m, 2H, –CH2–CH2–CH2), 2.02 (t, 2H, CH2–CO), 2.30 (s, 3H, Ar–CH3), 3.80 (t, 2H, N–CH2), 6.67 (s, 1H, pyrazole–H), 7.02–7.1 (d, d, J = 8 Hz, 2H, H-3, 4 anthra quione), 7.2 (s, 1H, H-1 anthraquinone), 7.3 (d, J = 8.5 Hz, 2H, H-3, 5 p-tolyl), 7.5 (d, J = 9 Hz, 2H, H-2, 6 p-tolyl), 7.8–8.1 (m, 8H, Ar–H), 10.1, (br. s, 2H, 2-NH); 13C-NMR (DMSO-d6) δ: 17.8 (CH2–CH2–CH2), 20.7 (Ar–CH3), 31.6 (–CH2CO), 47.3 (N–CH2), 106.3, 109.6, 118.0, 121.0, 126.1, 126.3, 126.4, 126.7, 128.7, 128.9, 129.4, 129.6, 133.0, 133.3, 133.7, 134.3, 134.9, 137.6, 139.2, 142.3, 154.7 (CF3, Ar–C and C=N), 173.9, 180.1, 183.3 (3C=O); MS: m/z (%): 672 (M+, 48.1).
3.1.8. N-(2-Isocyanatoethyl)-4-[5-(p-tolyl)-3-trifluoromethyl-1H-pyrazol-1-yl] benzene sulfonamide (4)
A mixture of 1 (0.01 mol) and 2-chloroethyl isocyanate (0.04 mol) was heated under reflux for 1 h. The excess 2-chloroethylisocyanate was removed under vacuum, after cooling, the reaction mixture was poured into ice cold water the solid formed was filtered off, washed with water and recrystallized from ethanol to give compound 4 in 85% yield; m.p.: 115–117 °C; IR (νmax/cm−1), 3321 (NH), 1740 (C=O); 1H NMR (CDCl3) δ: 2.30 (s, 3H, CH3–Ar), 3.60 (t, J = 6.5 Hz, 2H, CH2), 4.2 (t, J = 6.5 Hz, 2H, CH2), 6.67 (s, 1H, pyrazole-H), 7.09 (d, J = 10 Hz, 2H, H-3, 5 p-tolyl), 7.18 (d, J = 11 Hz, 2H, H-2, 6 p-tolyl), 7.4–8.03 (m, 5H, Ar–H and NH); 13C NMR (CDCl3) δ: 20.2 (CH3), 39.9, 41.8, (2CH2), 105.5, 124.1, 124.2, 127.4, 128.0, 128.5, 134.9, 138.7, 142.7, 144.1, 147.3, 150.5, 150.9 (CF3, Ar–C, C=N and N=C=O); MS: m/z (%): 450 (M+, 10.5).
3.1.9. N-(2-(3-(9,10-Dihydro-9,10-dioxoanthracen-2-yl) ureido) ethyl)-4-(5-(p-tolyl)-3-(trifluoro methyl)-1H-pyrazol-1-yl) benzene sulfonamide (5)
To a solution of compound 4 (0.01 mol) in ethanol (15 mL), 2-aminoanthraquinone 8 (0.01 mol) in DMF (3 mL) was added. The mixture was then heated to reflux for 5 h. the excess solvent was removed under vacuum and after cooling the precipitate formed was collected by filtration, washed with water and recrystallized from ethanol to give compound 5 in 68% yield; m.p.: 221–223 °C; IR (νmax/cm−1): 3435, 3345, 3200 (3NH), br. 1673 (3C=O); 1H NMR (DMSO-d6) δ: 2.3 (s, 3H, Ar–CH3), 3.7(t, J = 6.5 Hz, 2H, CH2–NHSO2–), 3.96 (t, J = 6.5 Hz, 2H, CH2–NH–C=O), 6.67 (s, 1H, pyrazole-H), 6.94–6.96 (d, d, J = 8.5 Hz, 2H, H-3, 4 anthraquinone), 7.3 (d, J = 8.8 Hz, 2H, H-3, 5 p-tolyl), 7.6 (d, J = 9 Hz, 2H, H-2, 6 p-tolyl), 7.84–8.08 (m, 9H, Ar–H), 8.25 (br. s, 3H, 3NH); 13C NMR (DMSO-d6) δ: 20.7 (CH3), 41.3, 43.2 (2C, 2CH2), 109.6, 118.0, 121.0, 125.1, 126.2, 126.3, 126.4, 128.7, 129.2, 129.4, 129.6, 133.0, 133.3, 133.7, 134.3, 134.8, 136.8, 139.1, 143.1, 145.4, 151.4, 151.8 (CF3, Ar–C and C=N), 154.7, 180.0, 183.3 (3C=O); MS: m/z (%): 673 (M+, 3.75).
3.1.10. N-[2-(2-Chloroethylamino) ethyl]-4-[5-(p-tolyl)-3-trifluoromethyl-1H-pyrazol-1-yl] benzene sulfonamide (6)
Bis (2-chloroethyl) amine hydrochloride (0.04 mol) was added to a solution of celecoxib 1 (0.02 mol) in dry toluene (10 mL) within 5 min in an ice bath and triethylamine (5 drops) was added and the reaction mixture was refluxed for 4 h. After the reaction was completed the solvent was concentrated, the residue was cooled and poured onto ice-cold water. The reaction mixture was then left at 5 °C overnight. The solid formed was collected by filtration and recrystallized from ethanol to give compound 6 in 84% yield; m.p.: 156–158 °C; IR (νmax/cm−1): 3340, 3234 (2NH), 1H NMR (DMSO-d6) δ: 2.2 (s, 3H, Ar–CH3), 2.5–2.55 (m, 6H, 3CH2NH), 3.8 (t, J = 6.5 Hz, 2H, CH2Cl), 6.7 (s, 1H, pyrazole-H), 7.10 (d, J = 8 Hz, 2H, H-3, 5 p-tolyl), 7.19 (d, J = 8 Hz, 2H, H-2, 6 p-tolyl), 7.5 (d, J = 8.8 Hz, 2H, H2, 6 benzene sulfonamide), 8.1 (d, J = 8.7 Hz, 2H, H-3, 5 benzene sulfonamide), 8.7 (s, 1H, NH), 11.02 (s, 1H, NH); 13C NMR (DMSO-d6) δ: 20.2 (Ar-CH3), 39.5, 40.0, 40.7, 42.0 (4 CH2), 105.5, 124.2, 124.4, 127.5, 128.2, 128.7, 135.0, 138.8, 142.8, 144.2, 150.6, 151.1 (CF3, Ar–C and C=N); MS: m/z (%): 523, 525 (M+, M+2, 75.6, 27).
3.1.11. N-[2-(2-(9,10-Dihydro-9,10-dioxoanthracen-2-yl) aminoethyl) aminoethyl]-4-[5-(p-tolyl)-3-trifluoromethyl-1H-pyrazol-1-yl] benzene sulfonamide (7)
A mixture of 6 (0.01 mol) in ethanol (15 mL), and 2-aminoanthraquinone 8 (0.01 mol) in DMF (3 mL) was heated under reflux for 8 h. The excess solvent was evaporated under vacuum and after cooling the solid formed was filtered off, washed well with water and recrystallized from methanol to give compound 7 in 73% yield; m.p.: 157–159 °C; IR (νmax/cm−1): 3415, 3351, 3234 (3NH), 1672 (2C=O), 1618 (C=C); 1H NMR (DMSO-d6) δ: 2.2 (s, 3H, Ar–CH3), 2.53–2.64 (m, 8H, 4CH2), 6.67 (s, 1H, pyrazole-H), 6.94–6.96 (d, d, J = 8.5 Hz, 2H, H-3,4 anthraquinone), 7.0 (d, J = 8 Hz, 2H, H-3, 5 p-tolyl), 7.1 (d, J = 8.8 Hz, 2H, H-2, 6 p-tolyl), 7.2–8.1 (m, 11H, Ar–H and 2NH); 8.3 (br. s, 1H, NH), 13C NMR (DMSO-d6) δ: 20.3 (Ar–CH3), 39.6, 40.1, 40.9, 42.2 (4CH2), 105.5, 117.2, 124.2, 124.4, 125.1, 126.6, 126.7, 127.5, 128.3, 128.9, 129.2, 129.6, 133.0, 134.0, 134.5, 135.0, 137.8, 138.6, 142.8, 143.1, 144.2, 150.6 (CF3, Ar–C and C=N), 173.8, 180.1, 183.3 (3CO); MS: m/z (%): 709, 711 (M+, M+2, 68.8, 27).
3.1.12. General Method for Preparation of 2- or 4-Chloro-N-(9,10-dihydro-9,10-dioxoanthracen-6-yl) alkanamide (9b,c)
A mixture of anthraquinone 8 (0.01 mol) and 1,2-chloropropionyl chloride, or chlorobutyryl chloride (0.04 mol) was heated under reflux for 1 h, the mixture was concentrated by evaporation under vacuum, after cooling the reaction mixture was poured onto ice cold water and the solid formed was filtered off, dried and recrystallized from ethanol to give the compounds 9b,c respectively.
3.1.13. 2-Chloro-N-(9,10-dihydro-9,10-dioxoanthracen-6-yl) propanamide (9b)
Yield 78%; Crystallized from ethanol; m.p.: 168 °C; IR (νmax/cm−1): 3348 (NH), 1716, 1671 (3C=O); 1H NMR (DMSO-d6) δ: 2.9 (d, J = 7.5 Hz, 3H, CH3), 5.5 (q, 1H, CHCl), 8.3 (s, 1H, H-1 anthraquinone), 9–9.7 (m, 6 H, Ar–H), 10.2 (s, 1H, NH); 13C NMR (DMSO-d6) δ: 17.2 (CH3), 50.7 (CH), 111.9, 119.2, 122.0, 124.0, 124.6, 128.2, 128.3, 128.7, 129.0, 129.4, 137.1, (Ar–C), 162.6 (CO), 176.7, 177.4 (2CO anthraquinone); MS: m/z (%): 313, 315 (M+, M+2, 34.4, 13.5).
3.1.14. 4-Chloro-N-(9,10-dihydro-9,10-dioxoanthracen-6-yl) butanamide (9c)
Yield 75 %; Crystallized from dilute ethanol; m.p.: 219 °C; IR (νmax/cm−1): 3340 (NH), 1698, 1667, 1649 (3C=O); 1H NMR (DMSO-d6) δ: 2.0 (m, 2H, CH2–CH2–CH2), 2.5 (t, J = 6.5 Hz, 2H, COCH2), 3.7 (t, J = 6.5 Hz, 2H, CH2Cl), 7.9–8.2 (m, 6 H, Ar–H), 8.4 (s, 1H, Ar, H-1), 10.6 (s, H, NH); 13C NMR (DMSO-d6) δ: 27.5 (CH2–CH2–CH2), 33.5 (COCH2), 62.9 (CH2Cl), 115.7, 123.6, 126.6, 126.7, 127.7, 128.4, 133.0, 134.1, 134.19, 134.5, 144.6 (Ar–C), 171 (C=O), 181.3, 182.4 (2C=O anthraquinone); MS: m/z (%): 327, 329 (M+, M+2, 28.4, 12.5).
3.1.15. N-(9,10-Dihydro-9,10-dioxoanthracen-2-yl-amino-carbonyl)-4-[5-(p-tolyl)-3-trifluoromethyl-1H-pyrazol-1-yl] benzene sulfonamide derivatives (10a–d)
General method: A mixture of 9a–d (0.01 mol) in ethanol (15 mL), and celecoxib 1 (0.01 mol) in DMF (3 mL) was heated under reflux for 4–5 h. The excess solvent was evaporated under vacuum and the solid formed was filtered off, washed with water and recrystallized from the proper solvent to give compounds 10a–d.
3.1.16. N-(9,10-Dihydro-9,10-dioxoanthracene-2-yl) aminoacetyl)-4-[5-(p-tolyl)-3-trifluoromethyl-1H-pyrazol-1-yl] benzene sulfonamide (10a)
Yield 70%; Recrystallized from chloroform; m.p.: 245–247 °C; IR (νmax/cm−1): 3345, 3114, (2NH), br. 1697 (3C=O); 1H NMR (DMSO-d6) δ: 2.5 (s, 3H, Ar–CH3), 4.37 (s, 2H, CH2), 6.68 (s, 1H, pyrazole-H), 6.94–6.96 (d, d, J = 8.5 Hz, 2H, H-3, 4 anthraquinone), 7.3 (d, J = 8 Hz, 2H, H-3, 5 p-tolyl), 7.6 (d, J = 8.5 Hz, 2H, H-2, 6 p-tolyl), 7.84–8.1 (m, 9H, Ar–H) 8.45 (s,1H, NH), 10.9 (s, 1H, NH); 13C NMR (DMSO-d6) δ: 21.3 (CH3), 43.0 (CH2), 106.3, 109.2, 109.6, 110.2, 116.5, 117.2, 118.0, 121.9, 125.1, 126.6, 126.7, 128.2, 129.6, 134.0, 134.3, 134.5, 143.9, 144.6, 145.2, 157.5 (CF3, Ar–C and C=N), 167.5, 181.3, 182.3 (3CO); MS: m/z (%): 644 (M+, 61.7).
3.1.17. N-[1-(9,10-Dihydro-9,10-dioxoanthracene-2-yl) aminocarbonyl) ethyl]-4-[5-(p-tolyl)-3-tri fluoromethyl-1H-pyrazol-1-yl] benzene sulfonamide (10b)
Yield 80%; Recrystallized from dil. ethanol; m.p.:132–135 °C; IR(νmax/cm−1): 3346, 3200 (2NH), 1690, 1673 (3C=O); 1H NMR (DMSO-d6) δ: 1.6 (d, J = 6.5 Hz, 3H, CH3), 2.28 (s, 3H, Ar–CH3), 4.7 (q, 1H, CH–CH3), 6.67 (s, 1H, pyrazol-H), 6.94–6.96 (d, d, J = 8.5 Hz, 2H, H-3, 4 anthraquinone), 7.3 (d, J = 8 Hz, 2H, H-3, 5 p-tolyl), 7.6 (d, J = 8.5 Hz, 2H, H-2, 6 p-tolyl), 7.84–8.1 (m, 9H, Ar–H) 8.46 (s, 1H, NH), 10.99 (s, 1H, NH); 13C NMR (DMSO-d6) δ: 16.5 (CH3), 20.7 (CH3–Ar), 52.7 (CH), 106.3, 109.6, 118.0, 121.9, 126.1, 126.3, 126.7, 128.7, 128.9, 129.6, 133.0, 133.3, 133.7, 134.3, 134.9, 137.6, 139.2, 142.3, 154.7 (CF3, Ar–C and C=N), 173.9, 180.1, 183.3 (3C=O); MS: m/z (%): 658 (M+, 30).
3.1.18. N-[3-(9,10-Dihydro-9,10-dioxoanthracene-2-yl) aminocarbonyl) propyl]-4-[5-(p-tolyl)-3-tri fluoromethyl-1H-pyrazol-1-yl] benzene sulfonamide (10c)
Yield 78%; Recrystallized from ethanol; m.p.: 113–115 °C; IR (νmax/cm−1): 3343, 3200 (2NH), 1690, 1673 (3C=O); 1H NMR (DMSO-d6) δ: 1.96 (m, 2H, CH2CH2CH2), 2.1 (t, J = 6.5 Hz, 2H, CH2CO) 2.2 (s, 3H, CH3–Ar), 2.6 (t, J = 6.5 Hz, 2H, N–CH2), 6.6 (s, 1H, pyrazole-H), 6.94–6.96 (d, d, J = 8.5 Hz, 2H, H-3, 4 anthraquinone), 7.3 (d, J = 2 Hz, 2H, H-3, 5 p-tolyl), 7.6 (d, J = 9 Hz, 2H, H-2, 6 p-tolyl), 7.84–8.1 (m, 9H, Ar-H), 8.4 (s, 1H, NH), 8.46 (s, 1H, NH); 13C NMR (DMSO-d6) δ: 21.3 (CH3), 29.7 (CH2–CH2–CH2), 32.8 (CH2CO), 48.5 (CH2-N), 106.3, 115.7, 124.7, 125.4, 125.7, 127.2, 127.5, 128.7, 129.7, 133.5, 133.6, 133.9, 134.2, 139.8, 141.3, 142.5, 144.6, 145.2, (CF3, Ar–C and C=N), 175.0, 180.0, 183.3 (3C=O); MS: m/z (%): 672 (M+, 46.6).
3.1.19. N-(9,10-Dihydro-9,10-dioxoanthracene-2-yl)aminooxalyl)-4-[5-(p-tolyl)-3-trifluoromethyl-1H-pyrazol-1-yl] benzene sulfonamide (10d)
Yield 72%; Recrystallized from chloroform/pet. ether; m.p.: 132–135 °C; IR (νmax/cm−1): 3415, 3245 (2NH), 1728, 1620 (4 C=O); 1H NMR (DMSO-d6) δ: 2.2 (s, 3H, Ar–CH3), 6.69 (s, 1H, pyrazole-H), 7.2 (d, J = 8 Hz, 2H, H-3, 5 p-tolyl), 7.5–8.1 (m, 13H, Ar-H), 8.7 (s, 1H, NH), 11.02 (s, 1H, NH); 13C NMR (DMSO-d6) δ: 106.3, 109.60, 110.2, 116.5, 117.2, 118.0, 121.9, 125.1, 126.6, 126.7, 128.2, 129.6, 133.0, 134.0, 134.3, 134.5, 143.9, 144.6, 145.2, 157.5 (CF3, Ar–C and C=N), 173.2, 180.1, 183.3 (4C=O); MS: m/z (%): 658 (M+, 44).
3.1.20. 2-(2-Isocyanatoethylamino)anthracene-9,10-dione (11)
A mixture of 8 (0.01 mol) and 2-chloroethyl isocyanate (0.04 mol) was heated under reflux for 1 h. The excess 2-chloroethylisocyanate was removed under vacuum, after cooling, the reaction mixture was poured onto ice cold water the solid formed was filtered off, washed with water and recrystallized from ethanol to give compound 11 in 75% yield; m.p.: 144 °C; IR (νmax/cm−1): 3343 (NH), 1735, 1708, 1668 (3C=O); 1H NMR (DMSO-d6) δ: 4.1 (t, J = 7.5 Hz, 2H, CH2NCO), 3.9 (t, J = 7.5 Hz, 2H, HN–CH2), 7.9–8.1 (m, 6H, Ar–H), 8.4 (s, 1H, Ar, H-1), 8.9 (s, 1H, NH); 13C NMR (DMSO-d6) δ: 49.9 (CH2), 58.7 (CH2), 115.7, 123.6, 126.6, 126.7, 127.7, 128.4, 133.0, 134.1, 134.19, 134.5, 144.6 (Ar–C), 173.9 (N=C=O), 181.3, 182.4 (2C=O anthraquinone); MS: m/z (%): 292 (M+, 14.5).
3.1.21. N-[2-(9,10-Dihydro-9,10-dioxoanthracene-2-yl-amino) ethylcarbamoyl]-4-[5-(p-tolyl)-3-trifluoromethyl-1H-pyrazol-1-yl] benzene sulfonamide (12)
A mixture of 11 (0.01 mol) in ethanol (15 mL), and celecoxib 1 (0.01 mol) in DMF (3 mL) was heated under reflux for 5 h. The excess solvent was evaporated under vacuum and after cooling the solid formed was filtered off, washed with water and recrystallized. Yield 75%; crystallized from dil. ethanol; m.p.: 162–164 °C; IR (νmax/cm−1): 3306, 3220 (3NH), 1671 (br., 3C=O); 1H NMR (DMSO-d6) δ: 2.2 (s, 3H, Ar-CH3), 3.4 (m, 2H, CH2), 4.1 (m, 2H, CH2), 6.6 (s, 1H, pyrazole-H), 7.02–7.1 (d, d, J = 8 Hz, 2H, H-3, 4 anthraquione), 7.2 (s, 1H, H-1, anthra quinone), 7.3 (d, J = 8.5 Hz, 2H, H-3, 5 p-toplyl), 7.5 (d, J = 9 Hz, 2H, H-2, 6 p-tolyl), 7.8–8.1 (m, 8H, Ar-H), 9.48 (s, 1H, NH), 10.09 (s, 1H, NH), 10.4 (s, 1H, NH); 13C NMR (DMSO-d6) δ: 20.7 (Ar–CH3), 43.8, 50.5 (2CH2), 106.3, 115.7, 123.5, 124.7, 125.4, 125.9, 126.5, 126.7, 127.2, 127.5, 128.7, 129.3, 133.5, 134.0, 139.8, 141.3, 142.5, 144.6, 145.2 (CF3, Ar–C and C=N), 175.2, 181.2, 183.3 (3C=O); MS: m/z (%): 673 (M+, 42).