r17 ia, p.37, 1982. ,
01 (s, lH, CH), Hz, vol.562, issue.75, p.33467 ,
SynthesisH Organic selenium compounds: Their Chemistry and Biologt, éd (c) Paulmier, C. Séelenium Reagents and Intermediates in Organic Synthesis, pp.1027-1063, 1967. ,
Phosphorus Sulfur Phosphorus SulfurAbdel-Mohsen, Sh.A. Phosphorus, Sulfur Silicon Relat. Elem, Chem. Soc. Jpn. Prim. D.; Kirsch, G. J.Chem. Soc., Perkin Trqns. I Tetrahedron Asymmetry Chem. Pharm. Bull. Phosphorus, Sulfur Silicon Relat. Elem. Tetrahedron Chem. Pharm. Bull. J. Prakt. Chem. Chem. Tetrahedron Tetrahedron Lett. J. Heteroqtclic.Chem. Tetrahedron Lett. Tetrahedron Tetrahedron J. Chem. Soc. Perkin Trans I Tetrahedron Lett, vol.72722393773527354329, issue.40, pp.387731517676525172480155921-3548257, 1167. ,
1983, I I 6, 1547 (c) Ried, W.; Kuhnt Synthesis, p.940, 1987. ,
Phosphorus, Sulfur and Silicon, Organic Syntheses, vol.824, p.91210, 1963. ,
1; f 986, J. Med. Chem. Fishwick, B. R.; Rowles, D. K J. Chem. Soc. Perkin Trans, vol.50, issue.171, p.901, 2007. ,
One-pot synthesis of substituted 3-amino-2-nitrothiophenes and selenophenes, Tetrahedron, vol.64, issue.14, p.3232 ,
DOI : 10.1016/j.tet.2008.01.078
Velnacrine thiaanalogues as potential agents for treating alzheimer's disease, Bioorganic & Medicinal Chemistry, vol.9, issue.11, p.2921, 1997. ,
DOI : 10.1016/S0968-0896(01)00171-7
Design and syntheses of 4-acylaminopyridine derivatives: Novel high affinity choline uptake enhancers II, Bioorganic & Medicinal Chemistry Letters, vol.5, issue.14, p.1495, 1995. ,
DOI : 10.1016/0960-894X(95)00242-L
Velnacrine thiaanalogues as potential agents for treating alzheimer's disease, Bioorganic & Medicinal Chemistry, vol.9, issue.11, p.2921, 2001. ,
DOI : 10.1016/S0968-0896(01)00171-7
124 A. Maul, Biochem. Pharmacol. Environ. Monit. Assess, vol.1, issue.153 ,
Put"nr; Upjohn, Chem. Ber. BEAbstr, vol.93, issue.643708, p.2743, 1960. ,
I4,g8l. 135 H*trr"h; Wolvekamp, J.Org.Chem.USSR Justus Liebigs Ann. Chem, vol.33, issue.1, pp.27-136, 1904. ,
Yield:93Vo; yellow solid; mp 195-197 "C. 'H NMR (250 MHz, CDC\): 6 = 2.40 (s, 3 H, CH3), 4.91 (s, 2 H, NH2), 6.75 (s, I H, CH), 5H42}J, vol.7, issue.18, pp.2-7 ,
Calcd forC,rH,oNrS:-C,61.26;H,4.70; N, 11.07. Found: C, 67, pp.4-67 ,
DMSo-d6): ô = 3.78 (s, 3 H, CHr), 6.49 (s,2H, NHt,6.80 (s, I H, CH), pp.98522-98524 ,
Calcd for C1,H7CIN2S: C, 56.29; H, 3.01; N, 1 1.94. Found: C, 56.42;H, 3.15; N, I 1, p.74 ,
Yield: 7 1 Vo; yef low solid; mp 224-226 "C. rH NMR (250 MHz, DMSO-d): ô = 1.90 (m,2H,CH), pp.797-846, 1953. ,
Found: C, 67.01;H,5.14; N, 8.37. Preparation of 9-Amino-2-(4-aryl)-6,7-dihydrothieno[3p- Dlquinolin-8(5Il)-ones 3a,b; General Procedure (Method A) NaOMe or ÇCO3 Q.2mmol) and CuCl (10.4 mmol) were added to a solution of 2 (10.4 mmol) in anhyd DMF (5 mL) and the mixture was heated at 80-90, pp.66-65 ,
6N2OS: C, 70.10; H,5.23; N, 9.08. Found: C, 70.26;H,5.12, pp.8-77 ,
'3C NMR (63 MHz, DMSO-d): ô = 21 ,
Calcd for C,sH1sN2S: C,73.43; H, 6.16; N, 9.51. Found: C, 73.41;H,5.84, pp.9-66 ,
9 -tetr ahydro-5ll-cyclohep- talDltNeno[23-e]pyridine (7a) Yield: 807o (Method B); mp 188-19033 (s, 3 H, CH3), ): ô = 1.53 (m, 2 H, CH), 1.58 (m, 2H, CJJ), 1.78 (m, 2H, CH)12 (s, 2 H, NH), 7 .27 (d, J = 1 .5 Hz, 2H,2x CH)5H2,2H,2 x CH). r3C NMR (63 MHz, p.75 ,
{2S: C,73.99 ,
71 (s, 1 H, CH), 7.79 (d, J ='7.5 Ha 2H, 2xCH). r3C NMR (63 MHz ,
Calcd for CrnHrsN2OS: C, 70.34; H,6.21 ,
4b) Yield:'7 ZVo: brown solid; mp 225-228'C. 'H NMR (250MH2, DMSO-d): ô = 1.55 (m, 2 H, CH2),2J1 (m, 2H,CH)46 (s, 1 H, OH),6.19 (s,2 H, NHr,6.94 (s, r}J,CH, Hz, 2 H, 2 x CH} 7. I 8 (d, J = 7 .5 Hz, 2 H, 2 x CH). r3C NMR (63 MHz, p.37, 1923. ,
Synthesis, Bioorg. Med. Chem.z0iù1. Bioorg. Med. Chem.2W5, vol.9, issue.13, pp.241-29211167, 1096. ,
URL : https://hal.archives-ouvertes.fr/hal-01690116
NO2S: C, 64.18; H,3.73; N, 5.76. Found: C, 64.32;H,3.59 ,
1620 (s), 1523 (s) cm-r. 'H NMR (250 MH4 DMSO-d): 6 =2.33 (s,3 H, CHr),5.56 (s, I H, CH), pp.2916-2927 ,
C,59.76; H, 3.09; N,5.36. Found: C, 59.&;H,3.26 ,
CDCI): ô = 5.96 (s, I H, CH),1.57 (s, 1H, CH), 94 (d, l = 7.5 Ha 2 H, 2 x CH), p.25 ,
Found: C, 54.46:H,2.67; N,9.56. 2-(1,1'-Biphenyl)-4-yl-7-hydroxythieno[32-D]pyridin-5 Yield: 807o; brown solid, C, issue.42g, pp.206-208 ,
l52l (s) cm'r. 'H NMR (250MH2, CDCI): 6 = 5.72 (s, 1 H, CH)53 (s, 1 H, CH),1.40 (d, J =7.5H2,2H,2 x CH), 1.48 (m,3 H, 3 x CH)72 (s,2H, NH and OH), 5H2,2H,2 x CH),7.78 (m,2H,2xCH), pp.3027-1664 ,
C, 71.45; H,4.lO; N, 4.39. Found: C, 71.26;H,4.45;N,4.52. 2 -t e rt -Butyl-7 -hydroxythieno [32-D ] pyridin -5(411) -one (2h) Yield:70Vo; brown solid, C, pp.2-212 ,
C, 59.17; H, 5.87; N, 6.27. Found: C, 59.05; H, 5.80;N, 6.07. 10-Hydroxy-5,6-dihydronaphtho[2',1' :4,5]thieno[3,2-D]pyri- din-8(7lI)-one (2i) Yield 767o: brown solid, C, pp.228-230 ,
NO2S: C, 65.35; H,4.31; N, 5.44. Found: C, 65.l6; H, 4.67 ,
]pyridine-5,7-diones, The Journal of Organic Chemistry, vol.69, issue.14, pp.4867-2357, 2004. ,
DOI : 10.1021/jo049769a
Synthesis, 276. (9) Liebscher, pp.32-41, 1026. ,
URL : https://hal.archives-ouvertes.fr/tel-01752590
2153-2156 @ Thieme Stungart, SynthesisNew York References and Notes Org. Biomol. Chem, issue.141, 2006. ,
Reactions of salicylaldehydes with bromonitromethane., CHEMICAL & PHARMACEUTICAL BULLETIN, vol.32, issue.11, pp.4260-74 ,
DOI : 10.1248/cpb.32.4260
(18) Reagents were purchased from ACROS Organics Thinlayer chromatography (TLC) was carried out by using SilicaGel 60F-254 plates and n-hexane-EtOAc (3:1) as an eluent. Melting points were determined on a Stuart Scientific SMP 3 capillary melting point apparatus and are uncorrected. IR spectra were performed in a Perkin Elmer Spectrum BxFT-IR spectrophotometer. Elemental analyses were conducted in a LECO CHNS 932 instrument. 2-(4-Chlorophenyl)-5-nitrothiophene (1): mp 127-724 "C (from EIOH) IR (KBr): v = 1534 (NOr), 1333 (NOz) cm r. 'HNMR (250MH2, DMSO-d): ô = 8, 10 Hz, 2 H, HPh). 13C NMR, pp.88721-58, 1986. ,
Calcd for Cr0II6CINO2S (239.68): C, 50. 1 1 ; H, 2.52; Cl, 14.79; N, 5.84; S, 13.38. Found: C, 50.20; H,2.60:. Ct, 14.70;N, 5.80; s, r3.32. 2-(4-Fluorophenyl)-5-nitrothiophene (2): mp 124-126 "C (from EIOH); mp,_, 129-130 oC.2 IR (KBr): v = 1536 (NOt, 1334 (NOr) cm-r, HPh),'1.63 (d, J = 4.25 Hz, I H), 7.33 (m,2 H, HPh). r3C NMR (62.9NItIz 116.5. 2-(4-Methylphenyl)-5-nitrothiophene (3): mp 86-87'C (from diisopropyl ether). IR (KBr): v = 15l0 (NOr), 1333 (NOr) cm-'. 'H NMR (250 MHz HPh), pp.149-57613034 ,
98 (s, lH, CH), pp.2-29 ,
73 (d, J:7 .5 IIz, 2H, 2xCII), 8.22 (s, 2H, NHr). t3C NMR (62.9 MHz, DMSO): ô 115 ,
Calcd for C1oH7CIN2O2S: C, 47.16; H,2.77 ,
One-pot synthesis of substituted 3-amino-2-nitrothiophenes and selenophenes, Tetrahedron, vol.64, issue.14, pp.3232-3235, 2008. ,
DOI : 10.1016/j.tet.2008.01.078
[ I, I | -biphe ny I ] -4 -yl -2 -nitr othiop he ne (2 g ) Yield:78Vo. Column chromatography with eluent cyclohexane/ethyl acetate (812) gave a brown solid; mp 126-128'C (dec) IR (KBr): 3a20 6),3305 (s), 1560 (s) cm-'. References and notes l, Morley, J. O Org. Biomol. Chem. J, 2006. ,
Preparation of Sodium Selenide Selenium (0.04 mol) was added to a solution of NaOH (0.224 mol) and sodium formaldehyde sulfoxylate (0.096 mol) in HrO, 1979. ,
HrNrSe: C,56.46;H,3.26: N, 11.33. Found: C, 56.66; H, 3.23 ,
30 (s, 3 H, CH,), 6.54 (s,2 H, NHr, 7.15 (s, 1 H, CH), '1.22 (d, J =7.5H2,2}l^,2 x CH) ,
Calcd for C12H16N2Se: C, 55.18; H, 3.86; N, 10.73, pp.10-78 ,
{2OSe: C, 52.00; H, 3.64; N, 10. I 1. Found: C,52.16: H, 3.78, pp.10-99 ,
70 eV): mlz = 282, p.202 ,
Calcd for CrH,rNrSe: C,47.58;H,5.32; N, 12.33. Found: C, 47, pp.12-28 ,
66 (s, 2 H, NHr), 7.41 (s, 1 H, CH) ,
70 eV): mlz = 293, pp.220-140 ,
OrSe: C, 45.22; H, 2.42; N, 14.38. Found: C, 45.84; H, 2.45, pp.14-27 ,
75 (m,2 H, CHr,6.09 (s, 2 H, NHt,7.39 (m,3 H, 3 x CH)80 (s, I H, CH), 3C NMR (63 MHz, p.49 ,
70 eV): mlz = 328, p.300 ,
uNrSe: C,62.39;H,4.93; N, 8.56. Found: C, 62.34;H,4.74); brown solid, ) Yield:78Vo (Method A), pp.97-216 ,
70 eV) : nil z = 342 lM'1, 327, pp.313-288 ,
800 (s) cm-'. rH NMR (250MH257 (s,I H, CH). r3C NMR (63 MHz, CDCI3): 6 =2.14 (m, 2 H, CW),2.17 (s, 3 H, CH),2.77 (m,2 H, CH2)5Hz,2H,2xCH}l.46(d,J =7.5H2,2H,2 x CH), pp.29491645-1561 ,
70 eV): ntl z = 328 lM'1, 247, I 63, I 15 ,
70 eV): ml z = 342, Ml, vol.326, issue.1, p.314 ,
Calcd for CtrH' rNrS e: C, 63.34 H, 5.32: N, 8.2 l. Found: C, 63.38; H,5.33 ,
70 eV): mlz= 356 [Ml, 341, 32'l, pp.115-91 ,
70 eV): ml z = 3M, pp.219-207 ,
Calcd for CtrHtrNrOSe: C, 60.51; H, 5.08 ,
70 eV): mlz=372 [Ml, pp.315219-207 ,
71(s, I H, CH) ,
Calcd for C'uHr3ClNrSe C,55.27;H,3.7'l; N, 8.06. Found: C, 55.54; H, 3.83 ,
Calcd for C17H15ClNrSe: C, 56.45; H,4.18; N, 7.74. Found: C, 56.61 ; H, 4.16, pp.7-49 ,
DMSO-d): ô = 1.57 (m,4 H, 2xCHr),1.79 (m, CH),2.38 (m,2 H, CH), pp.896-902 ,
70 eV): mlz = 376 [Ml, pp.347-207 ,
70 eV): mlz = 294 llv4+1, p.237 ,
34: H, 6.19; N, 9.55. Found: C, 57.30; H, 6.1 I ; N, 9.37. 9 -lrmino -2-t e n-butyl -3-methyl -5); beige solid, -tetrahydroselenophe- no[3,2-D]quinoline (4e) Yield:95Vo (Method A), p.94 ,
s, 1 H, CH, 2xCHr),2.48 (m,2}{,CH) r3C NMR (63 MHz, p.7470, 2011. ,
58.63; H, 6.56; N, 9.12. Found: C, 58.52; H, 6.40; N, 9.06. l0 -ltmino-2 -t e rt-butyl -3-methyl -6,7,8p -tetrahydro-5ll-cyclo- hepta[à]selenopheno); beige solid, pyridine (5e) Yield: 9IVo (Method A), pp.9-192 ,
26 (d, J =7.5 Hz 2H, 2 x CH). r3C NMR (63 MHz, CDCI3): 6 = 22 ,
Calcd forC,rH,rNrOrSe: C, 53.64; H,3.66; N, 11.73. Found: C, 53.46; H, 3.85 ,
1592 (t, 1561 (s), l5l I (s), 1338 (s) cm t, NMR (250MH2, CDCI): ô = 1.78 (m,4 H, 2xCHr),2.48 (m, 2H,CH), pp.293217-293224 ,
10 (s, I H, CH)5 Ha 2H, 2xCH). r3C NMR (63 MH4 CDCI): ô =22 ,
Calcd for CrrHrrNrOrSe: C, 54.85; H, 4.06; N, I 1.29. Found: C,55.12; H, 4.30 ,
Found: C, 55.84; H,4.59; N, 10.98. Reduction of the Nitro Group; General Procedure In a three-necked round-bottom flask equipped with a magnetic stirrer , condenser and stoppers, PdlC (5Vo,60 mg) was added to a solution of 2f, 3f or 4f (0.5 mmol) in absolute EIOH ( 10 mL) Hydrazine hydrate (98Vo,1.35 mmol) was added dropwise at r.t. and the mixture was stirred for 30 min. The mixture was then heated at reflux for 4 h, and every hour, additional hydrazine hydrate (1.35 mmol) was added. When the reaction was complete, EIOH was evaporated under vacuum and H2O (30 mL) was added. The precipitate was filtered, dried at r.t. until constant weight and recrystallized ,
Calcd forC,uHr5N3Se: C,58.54; H,4.61;N, 12.80. Found: C, 58.61; H,4.68, pp.12-79 ,
48 (s, 2 H, NHJ, 5.96 (s, 2 H, NHr), 6.58 (d, J = 7 .5 Hz, 2 H, 2 x CH), 7.33 (d, J = 7.5 Hz, 2 H, 2 x CH), pp.1-764821 ,
rNrSe: C, 59.65; H, 5.01; N, 12.28, pp.12-39 ,
1601 (s), 1529 (s), 1500 (s), 816 (s) cm-'. lH NMR (250}dH2, CDCI3): ô = 1.48 (m, 4 H, 2xCHr), IR, vol.1225671, issue.5, p.3341319329162847787147583345 ,
Calcd forCrrHrrN3Se: C,60.67; H,5.3'l;N, 11.79. Found: C, 60.62;H,5.27 ,
The use of microwave ovens for rapid organic synthesis, Tetrahedron Letters, vol.27, issue.3, pp.279-57, 1986. ,
DOI : 10.1016/S0040-4039(00)83996-9
Lit: mp: 147-148"C [4b] (NHr) cm-r; 'H nmr, (M). = (CnH,oNrSl*= I 78, pp.3443-3304 ,
|he mixture was then made basic with NaOH 307o and extracted with ethylacetate (3x20 mL) The combined organic layers were dried on anhydrous sodium sulfate, filtered and evaporated to give a solid, which was purified by silica gel column chromatography using a mixture of dichloromethane/methanol (9:l ) as eluent. 4-Amino-2,3-dimethyl-5,6,7,8-tetrahydrothieno[2,3-à]- quinolin-S-ol (4a) Yield : 83Vo; ocher crystalline powder; mp 182'C (dichloromethane/methanol 9:l); i: 3507 and 3383 (NHr, After the addition, the reaction mixture was refluxed for thCH3), 1278 (NHr), 1066 (OH) cm'':'H nmr: ô 1.20 (m, 4H,2xCHr), 1.60 (s,3H, CH.), 1.91 (m,3H, CH,+OH),2.13 (s, 3H, CH3), 4.14 (m, lH, CH-OH), 4.96 (2H, NHr) (M)* = (C,.H,6ON2S)*, pp.3118-2937 ,
25:H,6.34;N, 8.79. 4-Àmino-3-(4-chlorophenyl)-6,7-dihydro-5ll-cyclopenta[à]- thieno[3,2-e]pyridin e (5ùn =0). Y ield, 9 5 4o ; orange needles; mp 176'C (dichloromethane/methanol 9:1); tr: 3473 and, CHtgCHr), vol.703, issue.3308Cl 2, pp.70-104 ,
Anal. Calcd. for C,uH,.ClNrS: C, 63.89; H,4.36: N, 9.31. Found: C, 63.87;,H, 4.56; N,9.52. 4-Amino-3-(4-ùlorophenyl)-s,6t,8-tetrahydrothieno[2"3-à]- quinoline (5d/n=1) Yield 83Vo; orange needles; mp 179'C (dichloromethane/methanol 9:l); ir: 3488 and 3340 (NHr Yield 867o; orange needles, 3.0 (m, 2H, -N=C-CHz-),4.2 (s, 2H, NHr), 6.9 (s, 1H, thiophene proton),7.4 (m,4H,4xCH), pp.75-79, 1007. ,
L0-octahydro[1]benznthieno[2,3-D]- quinoline (5b) Yield 9T%o;brown needles; mp 218"C (dichloromethane/methanol 9:1), pp.3473-33612924, 2008. ,
9 (s, lH, thiophene proton (d,2H, 2xCH, J=8.5); 'rC nmr: ô 22 Anal. Calcd. for C"H'uNrOS: C, 68.89; H, 5.44 Yield 85Vo; orange needles, rH nmr: ô 1.9 (m, 4H,2xCHr), pp.2-7, 2008. ,
Re s, J.S. Tetrahedron, vol.47, issue.256, pp.62-11311, 2004. ,
Pierre Seckb a Laboratoire d'lngênieie Molêculaîre et Biochimie Pharmacologique, MEïZ France b Laboratoîre de Chimie, Fso.rltê des Sciences, de Ia Technologie et de Ia Communication lJniversité du Luxembourg 162a, avenue de Ia Faïencerie, L-1511, 2008. ,
Alzheimer disease Thiazole analogues of Tacrine Substituted [ 1,3 ]thiazolo[4,5-dl- [ 1,2,3]triazine Substituted 4-amino-1,3-thiazole-5- carbonitrile D, Thomae et al. Tetrahedrcn, vol.64, pp.9309-9314, 2008. ,
62 (s,3H, CHg), 7.22 (s,2H, NH2) 13C NMR ( 62.9 MHz, DMSO-d6 ) : ô 75, GC-MS (EI, 70 eV): mlz (%), pp.1711-1717 ,
1563 (s)cm-r. lH NMR (250MH2, DMSO-d6): ô 3.39 (t, l:S.OHz, 4H,2xCH),3.65 (t, l:5.oHz,4H,2xCHù,6.81 (s,2H, NH2), 13C NUn, vol.162, pp.33203205-1641 ,
57 (d, I :7.5 Hz, 2H, 2xCH),10.63 (s, 1H, NH) 13C NMR (62.9 MH4 DMSO-d6): ô 56, pp.216-119 ,
1543 (s)cm-1. tH NMR (25OMH4 DMSO-d6): ô 1.52 (m, 4H,2xCH),1.76 (m,2H,CHù,2.72 (m, 5H, CHz+CHa), 2.88 (m, 2H, CHù,6.22 (s,2H, NHz) 13C NMR (62.9 MHz, DMSO-d6): ô 15, pp.332332021564-767 ,
47 (t, l:s.o Hz, 4H, 2xCH), 4H, 2xCH), 6.01 (s, 2H, NH2). 13C NMR (62.9 MHz, pp.72-78 ,
1s26 (s)cm-l. rH NMR (250MH2, DMSO-d6): ô 1.51 (m, 4H,2xCH)65 (m,2H, CHù, 2.80 (m, 2H, CHù, 3.47 (t, J:5.0 Hz, 4H, 2xCH), 3.72 (t, J :5.o Hz, 4H, 2 x CH), 13c NMR (62.9 MHz, pp.1633156575161-32 ,
70 eV): mlz (%):190 (s7), pp.1-7 ,
Synthesis of substituted [1,3]thiazolo[4,5-b]pyridines and [1,3]thiazolo[4,5-d][1,2,3]triazines, Tetrahedron, vol.64, issue.39, pp.9309-9314, 2008. ,
DOI : 10.1016/j.tet.2008.07.017
70 eV): mlz (%), p.264 ,
2OO7,48,5267. 5. (a) Masquelin, 1; Obrecht, D, Tetrahedron 2OO1, vol.57, issue.153 ,
The reactions of some bromo-derivatives of compounds having reactive methylene groups with thioureas, and of some resultant thiouronium salts with base, Tetrahedron, vol.36, issue.18, p.2675, 1980. ,
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Praki Chem, J. W. Chem. Ber, vol.338, issue.10, pp.2363-1547, 1983. ,
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Pyrazole-related nucleosides. Synthesis and antiviral/antitumor activity of some substituted pyrazole and pyrazolo[4,3-d]-1,2,3-triazin-4-one nucleosides, Journal of Medicinal Chemistry, vol.35, issue.5, p.917, 1992. ,
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Synthesis, antihistaminic and cytotoxic activity of pyridothieno- and pyridodithienotriazines, European Journal of Medicinal Chemistry, vol.33, issue.11, p.887 ,
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