* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With sodium methylate In methanol at 65℃; Inert atmosphere
NaOMe (5M in MeOH, 3.5 mL, 17.6 mmol) followed by methylthioglycolate (1.8 mL, 20.1 mmol) was added to 3-methoxy-2-phenylacrylonitriles (2 g, 12.6 mmol). The reaction mixture was stirred and refluxed at 65 °C overnight. After the reaction, the mixture was filtered using celite and washed with methylene chloride. The crude compound was then purified by column chromatography (SiO2, hexane: EtOAc = 5:1) to give the white solid product 8–1 (1.5 g, 6.6 mmol, 52 percent yield in two steps): 1H NMR (300 MHz, CDCl3) δ 7.49–7.39 (m, 5H), 7.25 (s, 1H), 5.64 (br, 2H), 3.88 (s, 3H).
26%
With sodium methylate In methanol at 65℃; for 24 h;
Example 3 Methyl 3-amino-4-phenylthiophene-2-carboxylate 3-Methoxy-2-phenylacrylonitrile (17.9 g, 112.5 mmol) was dissolved in NaOMe (5 M in MeOH, 31.5 ml, 157.5 mmol), and then methyl thioglycolate (16 ml, 180.0 mmol) was added thereto. The mixture was heated with stirring at 65° C. for 24 hr. After the completion of the reaction was confirmed by thin layer chromatography (TLC), the reaction mixture was cooled to room temperature and filtered through Celite. The filtrate was washed with distilled water and extracted with dichloromethane. The organic layer was dried over anhydrous MgSO4 and filtered. The filtrate was distilled under reduced pressure, and the concentrate was purified by silica gel column chromatography (EtOAc:Hex=1:5) to give 5.1 g (21.9 mmol, 26percent yield in three steps) of the title compound. 1H NMR (300 MHz, CDCl3) δ 7.49-7.39 (m, 5H), 7.25 (s, 1H), 5.64 (br, 2H), 3.88 (s, 3H)
26%
With sodium methylate In methanol at 65℃; Inert atmosphere
General procedure: General: NaOMe (1.4 eq) in MeOH followed by methyl thioglycolate (1.6 eq) were added to 3-methoxy-2-phenylacrylonitrile (1 eq). The reaction mixture was stirred and refluxed at 65 °C overnight. After the reaction, the mixture was filtered using celite and washed with methylene chloride. The crude compound was then purified by column chromatography (SiO2, Hexane:EtOAc 5:1) to give white solid product 4 in 17-70percentyields.
Reference：
[1] Bulletin of the Korean Chemical Society, 2015, vol. 36, # 5, p. 1439 - 1451
[2] Patent: US2014/228565, 2014, A1, . Location in patent: Paragraph 0197; 0198
[3] European Journal of Medicinal Chemistry, 2014, vol. 85, p. 629 - 637
2
[ 22332-58-7 ]
[ 2365-48-2 ]
[ 82437-64-7 ]
Reference：
[1] Patent: US4710506, 1987, A,
3
[ 22252-92-2 ]
[ 2365-48-2 ]
[ 82437-64-7 ]
Reference：
[1] E-Journal of Chemistry, 2011, vol. 8, # 1, p. 368 - 372
[2] Journal of Heterocyclic Chemistry, 1982, vol. 19, p. 443 - 445
4
[ 140-29-4 ]
[ 82437-64-7 ]
Reference：
[1] Journal of Heterocyclic Chemistry, 1982, vol. 19, p. 443 - 445
[2] Patent: US2014/228565, 2014, A1,
[3] European Journal of Medicinal Chemistry, 2014, vol. 85, p. 629 - 637
[4] Bulletin of the Korean Chemical Society, 2015, vol. 36, # 5, p. 1439 - 1451
5
[ 22252-92-2 ]
[ 82437-64-7 ]
Reference：
[1] European Journal of Medicinal Chemistry, 2014, vol. 85, p. 629 - 637
[2] Bulletin of the Korean Chemical Society, 2015, vol. 36, # 5, p. 1439 - 1451
6
[ 2365-48-2 ]
[ 82437-64-7 ]
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 16, p. 2205 - 2208
7
[ 5841-70-3 ]
[ 82437-64-7 ]
Reference：
[1] Journal of Heterocyclic Chemistry, 1994, vol. 31, # 2, p. 305 - 312
8
[ 24944-46-5 ]
[ 2365-48-2 ]
[ 82437-64-7 ]
Reference：
[1] Journal of Heterocyclic Chemistry, 1994, vol. 31, # 2, p. 305 - 312
With urea; trichlorophosphate; In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; N,N-dimethyl-aniline; N,N-dimethyl-formamide;
Reference Example 52 2,4-Dichloro-7-phenylthieno[3,2-d]pyrimidine To 2.04 g (8.7 mmol) of <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> was added 2.62 g (43.7 mmol) of urea, and the resulting mixture was heated at 200 C. for 1.5 hours. The mixture was allowed to resume room temperature, and 50 ml of DMF was added thereto, followed by heating under reflux for one hour. After completion of the reaction, ice water was added to the reaction mixture, and crystals thus precipitated were filtered out, followed by drying, adding 10.76 g (70.2 mmol) of phosphorus oxychloride and 851 mg (7.0 mmol) of N,N-dimethylaniline thereto and heating under reflux for 3 hours. After completion of the reaction, ice water was added to the reaction mixture, and crystals thus precipitated were filtered to give 341 mg (yield: 13.9%) of the title compound. NMR (delta, CDCl3): 7.42-7.46 (1H, m), 7.49-7.54 (2H, m) 7.90-7.93 (2H, m), 8.17 (1H, s)
(a) A solution of methyl mercaptoacetate (11 ml) in methanol (50 ml) was added dropwise during 15 minutes to a stirred solution of sodium methoxide in methanol (27.9% w/v; 23 g) cooled in ice. After 25 minutes a solution of 3-chloro-2-phenylacrylonitrile (20 g) in methanol (80 ml) was added dropwise during 30 minutes to the stirred, cooled mixture. The mixture was allowed to warm to 20 and a solution of sodium methoxide in methanol (27.9% w/v; 23 g) was added. After 18 hours the solid product was collected by filtration, washed with water and dried to give the novel compound methyl 3-amino-4-phenylthiophene-2-carboxylate, m.p. 64-66.
General procedure: General: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (1 eq), CH(OEt)3 (14 eq) was added, followed by aniline 5 (1.9 eq) and AcOH (4 eq). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced solid was filtered and dried in vacuo to give the product thienopyrimidinone in 7-88% yields.
General procedure: General: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (1 eq), CH(OEt)3 (14 eq) was added, followed by aniline 5 (1.9 eq) and AcOH (4 eq). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced solid was filtered and dried in vacuo to give the product thienopyrimidinone in 7-88% yields.
General procedure: General: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (1 eq), CH(OEt)3 (14 eq) was added, followed by aniline 5 (1.9 eq) and AcOH (4 eq). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced solid was filtered and dried in vacuo to give the product thienopyrimidinone in 7-88% yields.
General procedure: General: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (1 eq), CH(OEt)3 (14 eq) was added, followed by aniline 5 (1.9 eq) and AcOH (4 eq). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced solid was filtered and dried in vacuo to give the product thienopyrimidinone in 7-88% yields.
General procedure: General: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (1 eq), CH(OEt)3 (14 eq) was added, followed by aniline 5 (1.9 eq) and AcOH (4 eq). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced solid was filtered and dried in vacuo to give the product thienopyrimidinone in 7-88% yields.
General procedure: General: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (1 eq), CH(OEt)3 (14 eq) was added, followed by aniline 5 (1.9 eq) and AcOH (4 eq). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced solid was filtered and dried in vacuo to give the product thienopyrimidinone in 7-88% yields.
With acetic acid; at 160℃;Inert atmosphere; Autoclave;
To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (100 mg, 0.43 mmol), CH(OEt)3 (1 mL) was added, followed by allylamine hydrochloride (93 mg, 0.99 mmol) and AcOH (0.1 mL). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced white crystals were filtered and dried in vacuo to give the title compound 4-1 (66 mg, 0.25 mmol, 58 % yield): 1HNMR (300 MHz, CDCl3) delta 8.11 (s, 1H), 7.84-7.79 (m, 3H), 7.50-7.44 (m, 2H), 7.41-7.36 (m, 1H), 6.08-5.95 (m, 1H), 5.34-5.24 (m, 2H), 4.72-4.67 (m, 2H); 13C NMR (100 MHz, CDCl3) delta 157.3, 154.3, 147.3, 138.1, 133.7, 131.9, 130.5,128.7, 128.3, 128.0, 124.9, 119.1, 48.0; LC/MS (ESI+): m/z: calcd for C15H12N2OS: 268.34, [M + H]+; found: 269.05
With acetic acid; at 160℃;Inert atmosphere; Autoclave;
General procedure: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (100 mg, 0.43 mmol), CH(OEt)3 (1 mL) was added, followed by allylamine hydrochloride (93 mg, 0.99 mmol) and AcOH (0.1 mL). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced white crystals were filtered and dried in vacuo to give the title compound 4-1 (66 mg, 0.25 mmol, 58 % yield): 1HNMR (300 MHz, CDCl3) delta 8.11 (s, 1H), 7.84-7.79 (m, 3H), 7.50-7.44 (m, 2H), 7.41-7.36 (m, 1H), 6.08-5.95 (m, 1H), 5.34-5.24 (m, 2H), 4.72-4.67 (m, 2H); 13C NMR (100 MHz, CDCl3) delta 157.3, 154.3, 147.3, 138.1, 133.7, 131.9, 130.5,128.7, 128.3, 128.0, 124.9, 119.1, 48.0; LC/MS (ESI+): m/z: calcd for C15H12N2OS: 268.34, [M + H]+; found: 269.05
With acetic acid; at 160℃;Inert atmosphere; Autoclave;
General procedure: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (100 mg, 0.43 mmol), CH(OEt)3 (1 mL) was added, followed by allylamine hydrochloride (93 mg, 0.99 mmol) and AcOH (0.1 mL). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced white crystals were filtered and dried in vacuo to give the title compound 4-1 (66 mg, 0.25 mmol, 58 % yield): 1HNMR (300 MHz, CDCl3) delta 8.11 (s, 1H), 7.84-7.79 (m, 3H), 7.50-7.44 (m, 2H), 7.41-7.36 (m, 1H), 6.08-5.95 (m, 1H), 5.34-5.24 (m, 2H), 4.72-4.67 (m, 2H); 13C NMR (100 MHz, CDCl3) delta 157.3, 154.3, 147.3, 138.1, 133.7, 131.9, 130.5,128.7, 128.3, 128.0, 124.9, 119.1, 48.0; LC/MS (ESI+): m/z: calcd for C15H12N2OS: 268.34, [M + H]+; found: 269.05
With acetic acid; at 160℃;Inert atmosphere; Autoclave;
General procedure: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (100 mg, 0.43 mmol), CH(OEt)3 (1 mL) was added, followed by allylamine hydrochloride (93 mg, 0.99 mmol) and AcOH (0.1 mL). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced white crystals were filtered and dried in vacuo to give the title compound 4-1 (66 mg, 0.25 mmol, 58 % yield): 1HNMR (300 MHz, CDCl3) delta 8.11 (s, 1H), 7.84-7.79 (m, 3H), 7.50-7.44 (m, 2H), 7.41-7.36 (m, 1H), 6.08-5.95 (m, 1H), 5.34-5.24 (m, 2H), 4.72-4.67 (m, 2H); 13C NMR (100 MHz, CDCl3) delta 157.3, 154.3, 147.3, 138.1, 133.7, 131.9, 130.5,128.7, 128.3, 128.0, 124.9, 119.1, 48.0; LC/MS (ESI+): m/z: calcd for C15H12N2OS: 268.34, [M + H]+; found: 269.05
With acetic acid; at 160℃;Inert atmosphere; Autoclave;
General procedure: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (100 mg, 0.43 mmol), CH(OEt)3 (1 mL) was added, followed by allylamine hydrochloride (93 mg, 0.99 mmol) and AcOH (0.1 mL). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced white crystals were filtered and dried in vacuo to give the title compound 4-1 (66 mg, 0.25 mmol, 58 % yield): 1HNMR (300 MHz, CDCl3) delta 8.11 (s, 1H), 7.84-7.79 (m, 3H), 7.50-7.44 (m, 2H), 7.41-7.36 (m, 1H), 6.08-5.95 (m, 1H), 5.34-5.24 (m, 2H), 4.72-4.67 (m, 2H); 13C NMR (100 MHz, CDCl3) delta 157.3, 154.3, 147.3, 138.1, 133.7, 131.9, 130.5,128.7, 128.3, 128.0, 124.9, 119.1, 48.0; LC/MS (ESI+): m/z: calcd for C15H12N2OS: 268.34, [M + H]+; found: 269.05
With acetic acid; at 160℃;Inert atmosphere; Autoclave;
General procedure: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (100 mg, 0.43 mmol), CH(OEt)3 (1 mL) was added, followed by allylamine hydrochloride (93 mg, 0.99 mmol) and AcOH (0.1 mL). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced white crystals were filtered and dried in vacuo to give the title compound 4-1 (66 mg, 0.25 mmol, 58 % yield): 1HNMR (300 MHz, CDCl3) delta 8.11 (s, 1H), 7.84-7.79 (m, 3H), 7.50-7.44 (m, 2H), 7.41-7.36 (m, 1H), 6.08-5.95 (m, 1H), 5.34-5.24 (m, 2H), 4.72-4.67 (m, 2H); 13C NMR (100 MHz, CDCl3) delta 157.3, 154.3, 147.3, 138.1, 133.7, 131.9, 130.5,128.7, 128.3, 128.0, 124.9, 119.1, 48.0; LC/MS (ESI+): m/z: calcd for C15H12N2OS: 268.34, [M + H]+; found: 269.05
With acetic acid; at 160℃;Inert atmosphere; Autoclave;
General procedure: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (100 mg, 0.43 mmol), CH(OEt)3 (1 mL) was added, followed by allylamine hydrochloride (93 mg, 0.99 mmol) and AcOH (0.1 mL). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced white crystals were filtered and dried in vacuo to give the title compound 4-1 (66 mg, 0.25 mmol, 58 % yield): 1HNMR (300 MHz, CDCl3) delta 8.11 (s, 1H), 7.84-7.79 (m, 3H), 7.50-7.44 (m, 2H), 7.41-7.36 (m, 1H), 6.08-5.95 (m, 1H), 5.34-5.24 (m, 2H), 4.72-4.67 (m, 2H); 13C NMR (100 MHz, CDCl3) delta 157.3, 154.3, 147.3, 138.1, 133.7, 131.9, 130.5,128.7, 128.3, 128.0, 124.9, 119.1, 48.0; LC/MS (ESI+): m/z: calcd for C15H12N2OS: 268.34, [M + H]+; found: 269.05
General procedure: General: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (1 eq), CH(OEt)3 (14 eq) was added, followed by aniline 5 (1.9 eq) and AcOH (4 eq). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced solid was filtered and dried in vacuo to give the product thienopyrimidinone in 7-88% yields.
With acetic acid; at 160℃;Inert atmosphere; Autoclave;
General procedure: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (100 mg, 0.43 mmol), CH(OEt)3 (1 mL) was added, followed by allylamine hydrochloride (93 mg, 0.99 mmol) and AcOH (0.1 mL). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced white crystals were filtered and dried in vacuo to give the title compound 4-1 (66 mg, 0.25 mmol, 58 % yield): 1HNMR (300 MHz, CDCl3) delta 8.11 (s, 1H), 7.84-7.79 (m, 3H), 7.50-7.44 (m, 2H), 7.41-7.36 (m, 1H), 6.08-5.95 (m, 1H), 5.34-5.24 (m, 2H), 4.72-4.67 (m, 2H); 13C NMR (100 MHz, CDCl3) delta 157.3, 154.3, 147.3, 138.1, 133.7, 131.9, 130.5,128.7, 128.3, 128.0, 124.9, 119.1, 48.0; LC/MS (ESI+): m/z: calcd for C15H12N2OS: 268.34, [M + H]+; found: 269.05
With acetic acid; at 160℃;Inert atmosphere; Autoclave;
General procedure: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (100 mg, 0.43 mmol), CH(OEt)3 (1 mL) was added, followed by allylamine hydrochloride (93 mg, 0.99 mmol) and AcOH (0.1 mL). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced white crystals were filtered and dried in vacuo to give the title compound 4-1 (66 mg, 0.25 mmol, 58 % yield): 1HNMR (300 MHz, CDCl3) delta 8.11 (s, 1H), 7.84-7.79 (m, 3H), 7.50-7.44 (m, 2H), 7.41-7.36 (m, 1H), 6.08-5.95 (m, 1H), 5.34-5.24 (m, 2H), 4.72-4.67 (m, 2H); 13C NMR (100 MHz, CDCl3) delta 157.3, 154.3, 147.3, 138.1, 133.7, 131.9, 130.5,128.7, 128.3, 128.0, 124.9, 119.1, 48.0; LC/MS (ESI+): m/z: calcd for C15H12N2OS: 268.34, [M + H]+; found: 269.05
With acetic acid; at 160℃;Inert atmosphere; Autoclave;
General procedure: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (100 mg, 0.43 mmol), CH(OEt)3 (1 mL) was added, followed by allylamine hydrochloride (93 mg, 0.99 mmol) and AcOH (0.1 mL). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced white crystals were filtered and dried in vacuo to give the title compound 4-1 (66 mg, 0.25 mmol, 58 % yield): 1HNMR (300 MHz, CDCl3) delta 8.11 (s, 1H), 7.84-7.79 (m, 3H), 7.50-7.44 (m, 2H), 7.41-7.36 (m, 1H), 6.08-5.95 (m, 1H), 5.34-5.24 (m, 2H), 4.72-4.67 (m, 2H); 13C NMR (100 MHz, CDCl3) delta 157.3, 154.3, 147.3, 138.1, 133.7, 131.9, 130.5,128.7, 128.3, 128.0, 124.9, 119.1, 48.0; LC/MS (ESI+): m/z: calcd for C15H12N2OS: 268.34, [M + H]+; found: 269.05
With acetic acid; at 160℃;Inert atmosphere; Autoclave;
General procedure: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (100 mg, 0.43 mmol), CH(OEt)3 (1 mL) was added, followed by allylamine hydrochloride (93 mg, 0.99 mmol) and AcOH (0.1 mL). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced white crystals were filtered and dried in vacuo to give the title compound 4-1 (66 mg, 0.25 mmol, 58 % yield): 1HNMR (300 MHz, CDCl3) delta 8.11 (s, 1H), 7.84-7.79 (m, 3H), 7.50-7.44 (m, 2H), 7.41-7.36 (m, 1H), 6.08-5.95 (m, 1H), 5.34-5.24 (m, 2H), 4.72-4.67 (m, 2H); 13C NMR (100 MHz, CDCl3) delta 157.3, 154.3, 147.3, 138.1, 133.7, 131.9, 130.5,128.7, 128.3, 128.0, 124.9, 119.1, 48.0; LC/MS (ESI+): m/z: calcd for C15H12N2OS: 268.34, [M + H]+; found: 269.05
With acetic acid; at 160℃;Inert atmosphere; Autoclave;
General procedure: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (100 mg, 0.43 mmol), CH(OEt)3 (1 mL) was added, followed by allylamine hydrochloride (93 mg, 0.99 mmol) and AcOH (0.1 mL). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced white crystals were filtered and dried in vacuo to give the title compound 4-1 (66 mg, 0.25 mmol, 58 % yield): 1HNMR (300 MHz, CDCl3) delta 8.11 (s, 1H), 7.84-7.79 (m, 3H), 7.50-7.44 (m, 2H), 7.41-7.36 (m, 1H), 6.08-5.95 (m, 1H), 5.34-5.24 (m, 2H), 4.72-4.67 (m, 2H); 13C NMR (100 MHz, CDCl3) delta 157.3, 154.3, 147.3, 138.1, 133.7, 131.9, 130.5,128.7, 128.3, 128.0, 124.9, 119.1, 48.0; LC/MS (ESI+): m/z: calcd for C15H12N2OS: 268.34, [M + H]+; found: 269.05
With acetic acid; at 160℃;Inert atmosphere; Autoclave;
General procedure: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (100 mg, 0.43 mmol), CH(OEt)3 (1 mL) was added, followed by allylamine hydrochloride (93 mg, 0.99 mmol) and AcOH (0.1 mL). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced white crystals were filtered and dried in vacuo to give the title compound 4-1 (66 mg, 0.25 mmol, 58 % yield): 1HNMR (300 MHz, CDCl3) delta 8.11 (s, 1H), 7.84-7.79 (m, 3H), 7.50-7.44 (m, 2H), 7.41-7.36 (m, 1H), 6.08-5.95 (m, 1H), 5.34-5.24 (m, 2H), 4.72-4.67 (m, 2H); 13C NMR (100 MHz, CDCl3) delta 157.3, 154.3, 147.3, 138.1, 133.7, 131.9, 130.5,128.7, 128.3, 128.0, 124.9, 119.1, 48.0; LC/MS (ESI+): m/z: calcd for C15H12N2OS: 268.34, [M + H]+; found: 269.05
General procedure: General: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (1 eq), CH(OEt)3 (14 eq) was added, followed by aniline 5 (1.9 eq) and AcOH (4 eq). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced solid was filtered and dried in vacuo to give the product thienopyrimidinone in 7-88% yields.
With acetic acid; at 160℃;Inert atmosphere; Autoclave;
General procedure: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (100 mg, 0.43 mmol), CH(OEt)3 (1 mL) was added, followed by allylamine hydrochloride (93 mg, 0.99 mmol) and AcOH (0.1 mL). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced white crystals were filtered and dried in vacuo to give the title compound 4-1 (66 mg, 0.25 mmol, 58 % yield): 1HNMR (300 MHz, CDCl3) delta 8.11 (s, 1H), 7.84-7.79 (m, 3H), 7.50-7.44 (m, 2H), 7.41-7.36 (m, 1H), 6.08-5.95 (m, 1H), 5.34-5.24 (m, 2H), 4.72-4.67 (m, 2H); 13C NMR (100 MHz, CDCl3) delta 157.3, 154.3, 147.3, 138.1, 133.7, 131.9, 130.5,128.7, 128.3, 128.0, 124.9, 119.1, 48.0; LC/MS (ESI+): m/z: calcd for C15H12N2OS: 268.34, [M + H]+; found: 269.05
With acetic acid; at 160℃;Inert atmosphere; Autoclave;
General procedure: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (100 mg, 0.43 mmol), CH(OEt)3 (1 mL) was added, followed by allylamine hydrochloride (93 mg, 0.99 mmol) and AcOH (0.1 mL). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced white crystals were filtered and dried in vacuo to give the title compound 4-1 (66 mg, 0.25 mmol, 58 % yield): 1HNMR (300 MHz, CDCl3) delta 8.11 (s, 1H), 7.84-7.79 (m, 3H), 7.50-7.44 (m, 2H), 7.41-7.36 (m, 1H), 6.08-5.95 (m, 1H), 5.34-5.24 (m, 2H), 4.72-4.67 (m, 2H); 13C NMR (100 MHz, CDCl3) delta 157.3, 154.3, 147.3, 138.1, 133.7, 131.9, 130.5,128.7, 128.3, 128.0, 124.9, 119.1, 48.0; LC/MS (ESI+): m/z: calcd for C15H12N2OS: 268.34, [M + H]+; found: 269.05
With acetic acid; at 160℃;Inert atmosphere; Autoclave;
General procedure: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (100 mg, 0.43 mmol), CH(OEt)3 (1 mL) was added, followed by allylamine hydrochloride (93 mg, 0.99 mmol) and AcOH (0.1 mL). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced white crystals were filtered and dried in vacuo to give the title compound 4-1 (66 mg, 0.25 mmol, 58 % yield): 1HNMR (300 MHz, CDCl3) delta 8.11 (s, 1H), 7.84-7.79 (m, 3H), 7.50-7.44 (m, 2H), 7.41-7.36 (m, 1H), 6.08-5.95 (m, 1H), 5.34-5.24 (m, 2H), 4.72-4.67 (m, 2H); 13C NMR (100 MHz, CDCl3) delta 157.3, 154.3, 147.3, 138.1, 133.7, 131.9, 130.5,128.7, 128.3, 128.0, 124.9, 119.1, 48.0; LC/MS (ESI+): m/z: calcd for C15H12N2OS: 268.34, [M + H]+; found: 269.05
With acetic acid; at 160℃;Inert atmosphere; Autoclave;
General procedure: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (100 mg, 0.43 mmol), CH(OEt)3 (1 mL) was added, followed by allylamine hydrochloride (93 mg, 0.99 mmol) and AcOH (0.1 mL). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced white crystals were filtered and dried in vacuo to give the title compound 4-1 (66 mg, 0.25 mmol, 58 % yield): 1HNMR (300 MHz, CDCl3) delta 8.11 (s, 1H), 7.84-7.79 (m, 3H), 7.50-7.44 (m, 2H), 7.41-7.36 (m, 1H), 6.08-5.95 (m, 1H), 5.34-5.24 (m, 2H), 4.72-4.67 (m, 2H); 13C NMR (100 MHz, CDCl3) delta 157.3, 154.3, 147.3, 138.1, 133.7, 131.9, 130.5,128.7, 128.3, 128.0, 124.9, 119.1, 48.0; LC/MS (ESI+): m/z: calcd for C15H12N2OS: 268.34, [M + H]+; found: 269.05
With acetic acid; at 160℃;Inert atmosphere; Autoclave;
General procedure: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (100 mg, 0.43 mmol), CH(OEt)3 (1 mL) was added, followed by allylamine hydrochloride (93 mg, 0.99 mmol) and AcOH (0.1 mL). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced white crystals were filtered and dried in vacuo to give the title compound 4-1 (66 mg, 0.25 mmol, 58 % yield): 1HNMR (300 MHz, CDCl3) delta 8.11 (s, 1H), 7.84-7.79 (m, 3H), 7.50-7.44 (m, 2H), 7.41-7.36 (m, 1H), 6.08-5.95 (m, 1H), 5.34-5.24 (m, 2H), 4.72-4.67 (m, 2H); 13C NMR (100 MHz, CDCl3) delta 157.3, 154.3, 147.3, 138.1, 133.7, 131.9, 130.5,128.7, 128.3, 128.0, 124.9, 119.1, 48.0; LC/MS (ESI+): m/z: calcd for C15H12N2OS: 268.34, [M + H]+; found: 269.05
General procedure: General: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (1 eq), CH(OEt)3 (14 eq) was added, followed by aniline 5 (1.9 eq) and AcOH (4 eq). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced solid was filtered and dried in vacuo to give the product thienopyrimidinone in 7-88% yields.
General procedure: General: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (1 eq), CH(OEt)3 (14 eq) was added, followed by aniline 5 (1.9 eq) and AcOH (4 eq). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced solid was filtered and dried in vacuo to give the product thienopyrimidinone in 7-88% yields.
General procedure: General: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (1 eq), CH(OEt)3 (14 eq) was added, followed by aniline 5 (1.9 eq) and AcOH (4 eq). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced solid was filtered and dried in vacuo to give the product thienopyrimidinone in 7-88% yields.
General procedure: General: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (1 eq), CH(OEt)3 (14 eq) was added, followed by aniline 5 (1.9 eq) and AcOH (4 eq). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced solid was filtered and dried in vacuo to give the product thienopyrimidinone in 7-88% yields.
General procedure: General: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (1 eq), CH(OEt)3 (14 eq) was added, followed by aniline 5 (1.9 eq) and AcOH (4 eq). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced solid was filtered and dried in vacuo to give the product thienopyrimidinone in 7-88% yields.
General procedure: General: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (1 eq), CH(OEt)3 (14 eq) was added, followed by aniline 5 (1.9 eq) and AcOH (4 eq). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced solid was filtered and dried in vacuo to give the product thienopyrimidinone in 7-88% yields.
3-(4-Chlorophenyl)-7-phenylthieno[3,2-d]pyrimidin-2,4(1H,3H)-dione Methyl 3-amino-4-phenylthiophene-2-carboxylate (400 mg, 1.71 mmol), triethylamine (0.04 ml, 0.43 mmol), and 4-chlorophenyl isocyanate (0.39 ml, 3.16 mmol) were dissolved in 1,4-dioxane (10 ml) in a reaction vessel. The mixture was heated with stirring at 90 C. for 3 days. After the completion of the reaction was confirmed by TLC, the reaction mixture was cooled to room temperature and filtered. The filtered solid was dissolved in a 10% sodium hydroxide/methanol (3 ml/12 ml) solution and refluxed with stirring at 100 C. overnight. After completion of the reaction, the reaction solution was cooled to room temperature, acidified with 3 N hydrochloric acid, and filtered to give 548 mg (1.54 mmol, 90% yield) of the title compound as a solid. 1H NMR (300 MHz, CDCl3) delta 7.74 (s, 1H), 7.65 (s, 1H), 7.45-7.61 (m, 7H), 7.27-7.30 (m, 2H)
With sodium methylate; In methanol; at 65℃;Inert atmosphere;
NaOMe (5M in MeOH, 3.5 mL, 17.6 mmol) followed by methylthioglycolate (1.8 mL, 20.1 mmol) was added to 3-methoxy-2-phenylacrylonitriles (2 g, 12.6 mmol). The reaction mixture was stirred and refluxed at 65 C overnight. After the reaction, the mixture was filtered using celite and washed with methylene chloride. The crude compound was then purified by column chromatography (SiO2, hexane: EtOAc = 5:1) to give the white solid product 8-1 (1.5 g, 6.6 mmol, 52 % yield in two steps): 1H NMR (300 MHz, CDCl3) delta 7.49-7.39 (m, 5H), 7.25 (s, 1H), 5.64 (br, 2H), 3.88 (s, 3H).
26%
With sodium methylate; In methanol; at 65℃; for 24h;
Example 3 Methyl 3-amino-4-phenylthiophene-2-carboxylate 3-Methoxy-2-phenylacrylonitrile (17.9 g, 112.5 mmol) was dissolved in NaOMe (5 M in MeOH, 31.5 ml, 157.5 mmol), and then methyl thioglycolate (16 ml, 180.0 mmol) was added thereto. The mixture was heated with stirring at 65 C. for 24 hr. After the completion of the reaction was confirmed by thin layer chromatography (TLC), the reaction mixture was cooled to room temperature and filtered through Celite. The filtrate was washed with distilled water and extracted with dichloromethane. The organic layer was dried over anhydrous MgSO4 and filtered. The filtrate was distilled under reduced pressure, and the concentrate was purified by silica gel column chromatography (EtOAc:Hex=1:5) to give 5.1 g (21.9 mmol, 26% yield in three steps) of the title compound. 1H NMR (300 MHz, CDCl3) delta 7.49-7.39 (m, 5H), 7.25 (s, 1H), 5.64 (br, 2H), 3.88 (s, 3H)
26%
With sodium methylate; In methanol; at 65℃;Inert atmosphere;
General procedure: General: NaOMe (1.4 eq) in MeOH followed by methyl thioglycolate (1.6 eq) were added to 3-methoxy-2-phenylacrylonitrile (1 eq). The reaction mixture was stirred and refluxed at 65 C overnight. After the reaction, the mixture was filtered using celite and washed with methylene chloride. The crude compound was then purified by column chromatography (SiO2, Hexane:EtOAc 5:1) to give white solid product 4 in 17-70%yields.
Example 4 3-Amino-N-(4-methoxyphenyl)-4-phenylthiophene-2-carboxamide p-Anisidine (29 mg, 0.24 mmol) was dissolved in toluene (2 ml) in a reaction vessel, and trimethylaluminum (2 M in TIIF, 0.12 ml) was added thereto at 0 C. After stirring for 10 min, to the mixture was added <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (50 mg, 0.21 mmol). The resulting mixture was heated to reflux at 120 C. for 16 hr. The completion of the reaction was confirmed by TLC. The reaction mixture was allowed to cool to room temperature, extracted with EtOAc, dried over anhydrous MgSO4, and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (hexane:EtOAc=5:1) to give (57 mg, 0.18 mmol, 84% yield) of the title compound. 1H NMR (300 MHz, CDCl3) delta 7.47-7.37 (m, 7H), 7.16 (s, 1H), 7.07 (brs, 1H), 6.93-6.89 (m, 2H), 5.86 (brs, 2H), 3.81 (s, 3H)
With acetic acid; orthoformic acid triethyl ester; at 160℃; for 18h;
Compound 1: 3,7-Diphenylthieno[3,2-d]pyrimidin-4(3H)-one Methyl 3-amino-4-phenylthiophene-2-carboxylate (100 mg, 0.43 mmol), triethyl orthoformate (1 ml), aniline (76 mg, 0.81 mmol), and acetic acid (0.1 ml) were placed in a pressure bottle. The mixture was heated with stirring at 160 C. for 18 hr. After the completion of the reaction was confirmed by TLC, the reaction mixture was cooled to room temperature and solidified with diethyl ether and EtOAc to give 42 mg (0.14 mmol, 33% yield) of the title compound as a final product. 1H NMR (400 MHz, CDCl3) delta 8.53 (s, 1H), 8.51 (s, 1H), 8.01 (d, J=7.2 Hz, 2H), 7.63-7.55 (m, 5H), 7.52 (t, J=7.6 Hz, 2H), 7.42 (t, J=7.4 Hz, 1H)
General procedure: General: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (1 eq), CH(OEt)3 (14 eq) was added, followed by aniline 5 (1.9 eq) and AcOH (4 eq). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced solid was filtered and dried in vacuo to give the product thienopyrimidinone in 7-88% yields.
General procedure: General: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (1 eq), CH(OEt)3 (14 eq) was added, followed by aniline 5 (1.9 eq) and AcOH (4 eq). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced solid was filtered and dried in vacuo to give the product thienopyrimidinone in 7-88% yields.
General procedure: General: To a pressure bottle containing <strong>[82437-64-7]methyl 3-amino-4-phenylthiophene-2-carboxylate</strong> (1 eq), CH(OEt)3 (14 eq) was added, followed by aniline 5 (1.9 eq) and AcOH (4 eq). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced solid was filtered and dried in vacuo to give the product thienopyrimidinone in 7-88% yields.
General procedure: General: To a pressure bottle containing methyl 3-amino-4-phenylthiophene-2-carboxylate (1 eq), CH(OEt)3 (14 eq) was added, followed by aniline 5 (1.9 eq) and AcOH (4 eq). The reaction mixture was stirred and refluxed at 160 C overnight. After the reaction, the mixture was evaporated then solidified with ether. The produced solid was filtered and dried in vacuo to give the product thienopyrimidinone in 7-88% yields.
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