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Synthesis of 10-Amino-5,6,7,9-tetrahydro-1-thia-4,9-diazacyclohepta[f]inden-8-one Derivatives using Schmit Reaction

슈미트 반응을 이용한 10-amino-5,6,7,9-tetrahydro-1-thia-4,9-diazacyclohepta[ f]inden-8-one 유도체의 합성

  • Published : 2009.06.20

Abstract

Keywords

Alzheimer’s disease;Acetylcholinesterase inhibitor;Schmit reaction; Thienopyridine derivative

EXPERIMENTAL

All products were characterized by IR, 1H NMR, MS and elemental analysis. Melting points were measured by using the capillary tubes on Büchi apparatus and are uncorrected. Each compound of the reactions was checked on thin-layer chromatography of Merck Kieselgel 60F254 and purified by column chromatography using Merck silica gel (70-230 mesh). IR spectra were recorded on the FT-IR Brucker Tensor 27. The 1H NMR spectra were recorded on Bruker DRX-300 FTNMR spectrometer (300 MHz) with Me4Si as internal standard and chemical shifts are given in ppm (δ). Electron ionization mass spectra were recorded on a HP 59580 B spectrometer. Elemental analyses were performed on a Carlo Erba 1106 elemental analyzer.

General procedure for the preparation of 10-amino-5,6,7,9-tetrahydro-1-thia-4,9-diazacyclohe pta[f]inden-8-one derivatives (4):

To a solution of 8 (0.01 mole) in concentrated H2SO4 (10 mL) and CHCl3 (10 mL), sodium azide (0.03 mole) was slowly added over 1 h. The solution was stirred for 5 h at room temperature. The reaction mixture was basified with dilute NH4OH and extracted with CHCl3. After evaporation the precipitate was filtered and recrystallized from EtOH.

10-Amino-5,6,7,9-tetrahydro-1-thia-4,9-diazac yclohepta[f]inden-8-one (4a):

Yield 58%; mp 231 ℃ (dec); IR (KBr): 1670 cm-1; 1H NMR (DMSO-d6): δ 8.71 (s, 1H, NH), 7.78 (d, J = 5.9 Hz, 1H, thiophene H-2), 7.24 (d, J = 5.9 Hz, 1H, H-3), 6.18 (s, 2H, NH2), 2.78 (m, 2H, H-5), 2.13-2.07 (m, 4H, H-6 and H-7); MS: (m/z) 233 (M+), 204, 190. Anal. Calcd. for C11H11N3OS: C, 56.63; H, 3.14; N, 18.01. Found: C, 56.50; H, 3.30; N, 18.22.

1,3,4,5-Tetrahydro-9-thia-1,2,6-triazacyclopen ta[d]acenaphthylene (9a):

Yield 14%; mp 283-284 ℃; 1H NMR (DMSO-d6): 13.30 (s, 1H, NH), 7.91 (d, J = 5.9 Hz, 1H, thiophene H-8), 7.59 (d, J = 5.9 Hz, 1H, H-9), 3.00-2.94 (m, 4H, H-3 and H-5), 2.19 (q, 2H, H-4); MS: (m/z) 215 (M+), 186, 160. Anal. Calcd. for C11H9N3S: C, 61.37; H, 4.21; N, 19.52. Found: C, 61.49; H, 4.10; N, 19.70.

10-Amino-6,6-dimethyl-5,6,7,9-tetrahydro-1-thia-4,9-diazacyclohepta[f]inden-8-one (4b):

Yield 52%; mp 227 ℃ (dec); 1H NMR (DMSO-d6): 8.77 (s, 1H,NH), 7.76 (d, J = 5.9 Hz, 1H, thiophene H-2), 7.29 (d, J = 5.9 Hz, 1H, H-3), 6.18 (s, 2H, NH2), 2.90 (s, 2H, H-5), 2.58 (s, 2H, H-7), 1.00 (s, 6H, diMe); MS: (m/z) 261 (M+), 246, 218, 178, 135. Anal. Calcd. for C13H15N3OS: C, 59.75; H, 5.78; N, 16.08. Found: C, 59.90; H, 5.59; N, 16.20.

10-Amino-6-phenyl-5,6,7,9-tetrahydro-1-thia-4,9-diazacyclohepta[f]inden-8-one (4c):

Yield 62%; mp 196-197 ℃; 1H NMR (DMSO-d6): 8.94 (s, 1H,NH), 7.81 (d, J = 6.0 Hz, 1H, thiophene H-2), 7.29-7.22 (m, 6H, H-3 and phenyl), 6.27 (s, 2H, NH2), 3.65 (m, 1H, H-6), 3.15 (m, 1H, H-5a), 2.98 (m, 1H, H-5b), 2.49 (m, 1H, H-7a), 2.29 (m, 1H, H-7b); MS: (m/z) 309 (M+), 284, 179. Anal. Calcd. for C17H15N3OS: C, 66.00; H, 4.89; N, 13.58. Found: C, 65.84; H, 4.73; N, 13.70.

10-Amino-6-p-tolyl-5,6,7,9-tetrahydro-1-thia-4,9-diazacyclohepta[f]inden-8-one (4d):

Yield 44%; mp 169-171 ℃; 1H NMR (DMSO-d6): δ 8.92 (s, 1H,NH), 7.81 (d, J = 6.0 Hz, 1H, thiophene H-2), 7.29 (d, J = 5.9 Hz, 1H, H-3), 7.25 (d, 2H, phenyl H-2’and H-6’), 7.09 (d, 2H, phenyl H-3’and H-5’), 6.26 (s, 2H, NH2), 3.57 (m, 1H, H-6), 3.12 (m, 1H, H-5a), 2.96 (m, 1H, H-5b), 2.50 (m, 1H, H-7a), 2.27-2.20 (m, 4H, H-7b and Me); MS: (m/z) 323 (M+), 295, 280, 179, 145. Anal. Calcd. for C18H17N3OS: C, 66.85; H, 5.30; N, 12.99. Found: C, 66.99; H, 5.48; N, 13.19.

4-p-Tolyl-1,3,4,5-tetrahydro-9-thia-1,2,6-triaza cyclopenta[d]acenaphthylene (9d):

Yield 10%; mp 246-247 ℃; 1H NMR (DMSO-d6): δ 13.60 (s, 1H, NH), 7.95 (d, J = 5.9 Hz, 1H, thiophene H-8), 7.34 (d, J = 5.9 Hz, 1H, H-9), 7.24 (d, 2H, phenyl H-2’and H-6’), 7.07 (d, 2H, phenyl H-3’and H-5’), 3.40 (m, 1H, H-4), 3.11-2.95 (m, 4H, H-3 and H-5), 2.22(s, 3H, Me); MS: (m/z) 305 (M+), 299, 286. Anal. Calcd. for C18H15N3S: C,70.79; H, 4.95; N, 13.76. Found: C, 70.62; H, 4.76; N, 13.90.

10-Amino-6-(4-chlorophenyl)-5,6,7,9-tetrahyd ro-1-thia-4,9-diazacyclohepta[f]inden-8-one (4e):

Yield 65%; mp 189-190 ℃; 1H NMR (DMSO-d6): δ 8.97 (s, 1H,NH), 7.83 (d, J = 5.9 Hz, 1H, thiophene H-2), 7.48 (d, 2H, phenyl H-3’and H-5’), 7.31 (d, 2H, phenyl H-2’and H-6’), 7.28 (d, J = 5.9 Hz, 1H, H-3), 6.35 (s, 2H, NH2), 3.67 (m, 1H, H-6), 3.16 (m, 1H, H-5a), 2.98 (m, 1H, H-5b), 2.49 (m, 1H, H-7a), 2.28 (m, 1H, H-7b); MS: (m/z) 344 (M+), 316, 300, 219, 180, 165. Anal. Calcd. for C17H14ClN3OS: C, 59.39; H, 4.10; N, 12.22. Found: C, 59.22; H, 4.28; N, 12.10.

10-Amino-6-(4-bromophenyl)-5,6,7,9-tetrahyd ro-1-thia-4,9-diazacyclohepta[f]inden-8-one (4f):

Yield 56%; mp 252-254 ℃; 1H NMR (DMSO-d6): δ 8.96 (s, 1H,NH), 7.82 (d, J = 5.9 Hz, 1H, thiophene H-2), 7.47 (d, 2H, phenyl H-3’and H-5’), 7.31 (d, 2H, phenyl H-2’and H-6’), 7.27 (d, J = 5.9 Hz, 1H, H-3), 6.30 (s, 2H, NH2), 3.66 (m, 1H, H-6), 3.15 (m, 1H, H-5a), 2.96 (m, 1H, H-5b), 2.49 (m, 1H, H-7a), 2.26 (m, 1H, H-7b); MS: (m/z) 388 (M+), 360, 218, 190, 179. Anal. Calcd. for C17H14BrN3OS: C, 52.59; H, 3.63; N, 10.82. Found: C, 52.75; H, 3.48; N, 11.01.

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