CB 300919; 4-[[[7-氯-3,4-二氢-3-甲基-2-[(4-甲基-1-哌嗪基)甲基]-4-氧代-6-喹唑啉基]甲基]-2-丙炔-1-基氨基]-N-(3-吡啶基甲基)苯甲酰胺合成路线 （共 21 条）
反应条件
1: tert-butyl 4-[N-[7-chloro-3-methyl-2-(4-methylpiperazin-1-ylmethyl)-4-oxo-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl)amino]benzoate With trifluoroacetic acid in dichloromethane T=20°C; 0.916667 h; 2: 3-pyridinylmethylamine With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine in DMF (N,N-dimethyl-formamide) T=0 - 20°C; 3 h; Under argon;
参考文献
Cancer Research Technology Limited
Patent: US6699861 B1, 2004 ;
Location in patent: Page column 32 ;
US 6699861 B1
反应条件
1: 86 percent / pyridine / ethyl acetate / 18 h / 20 °C 2: 48 percent / glacial AcOH; Br2 / 1.5 h / 15 °C 3: 94 percent / AcOH; conc. HCl / 24 h / 118 °C 4: 6.52 g / N-methylpyrrolidinone / 2 h / 163 °C 5: 93 percent / aq. KOH; H2O2 / 2 h / 130 °C 6: 97 percent / tetrahydrofuran / 6 h / 20 °C 7: 90 percent / DMAP / 3 h / 80 °C 8: 90 percent / pyridine / dimethylformamide / 2 h / 20 °C 9: 0.230 g / methanol; tetrahydrofuran / 26 h / 20 °C 10: 76 percent / 48percent aq. HBr / 7 h / 120 °C 11: 98 percent / DMAP; Et3N / CH2Cl2 / 0.5 h / 20 °C 12: 51 percent / NBS; dibenzoyl peroxide / CCl4 / 3.83 h / 85 °C / Irradiation 13: 73 percent / 2,6-lutidine / dimethylformamide / 5.5 h / 120 °C 14: 80 percent / aq. NaOH / tetrahydrofuran / 1 h / 20 °C 15: 94 percent / Et3N / CH2Cl2 / 0.92 h 16: 77 percent / CH2Cl2 / 2.5 h / 20 °C 17: 0.142 g / TFA / CH2Cl2 / 0.92 h / 20 °C 18: PyBOP; diisopropylethylamine / dimethylformamide / 3 h View Scheme
参考文献
Bavetsias; Skelton; Yafai; Mitchell; Wilson; Allan; Jackman
Journal of Medicinal Chemistry, 2002 , vol. 45, # 17 p. 3692 - 3702
反应条件
1: 48 percent / glacial AcOH; Br2 / 1.5 h / 15 °C 2: 94 percent / AcOH; conc. HCl / 24 h / 118 °C 3: 6.52 g / N-methylpyrrolidinone / 2 h / 163 °C 4: 93 percent / aq. KOH; H2O2 / 2 h / 130 °C 5: 97 percent / tetrahydrofuran / 6 h / 20 °C 6: 90 percent / DMAP / 3 h / 80 °C 7: 90 percent / pyridine / dimethylformamide / 2 h / 20 °C 8: 0.230 g / methanol; tetrahydrofuran / 26 h / 20 °C 9: 76 percent / 48percent aq. HBr / 7 h / 120 °C 10: 98 percent / DMAP; Et3N / CH2Cl2 / 0.5 h / 20 °C 11: 51 percent / NBS; dibenzoyl peroxide / CCl4 / 3.83 h / 85 °C / Irradiation 12: 73 percent / 2,6-lutidine / dimethylformamide / 5.5 h / 120 °C 13: 80 percent / aq. NaOH / tetrahydrofuran / 1 h / 20 °C 14: 94 percent / Et3N / CH2Cl2 / 0.92 h 15: 77 percent / CH2Cl2 / 2.5 h / 20 °C 16: 0.142 g / TFA / CH2Cl2 / 0.92 h / 20 °C 17: PyBOP; diisopropylethylamine / dimethylformamide / 3 h View Scheme
参考文献
Bavetsias; Skelton; Yafai; Mitchell; Wilson; Allan; Jackman
Journal of Medicinal Chemistry, 2002 , vol. 45, # 17 p. 3692 - 3702
反应条件
1: 6.52 g / N-methylpyrrolidinone / 2 h / 163 °C 2: 93 percent / aq. KOH; H2O2 / 2 h / 130 °C 3: 97 percent / tetrahydrofuran / 6 h / 20 °C 4: 90 percent / DMAP / 3 h / 80 °C 5: 90 percent / pyridine / dimethylformamide / 2 h / 20 °C 6: 0.230 g / methanol; tetrahydrofuran / 26 h / 20 °C 7: 76 percent / 48percent aq. HBr / 7 h / 120 °C 8: 98 percent / DMAP; Et3N / CH2Cl2 / 0.5 h / 20 °C 9: 51 percent / NBS; dibenzoyl peroxide / CCl4 / 3.83 h / 85 °C / Irradiation 10: 73 percent / 2,6-lutidine / dimethylformamide / 5.5 h / 120 °C 11: 80 percent / aq. NaOH / tetrahydrofuran / 1 h / 20 °C 12: 94 percent / Et3N / CH2Cl2 / 0.92 h 13: 77 percent / CH2Cl2 / 2.5 h / 20 °C 14: 0.142 g / TFA / CH2Cl2 / 0.92 h / 20 °C 15: PyBOP; diisopropylethylamine / dimethylformamide / 3 h View Scheme
参考文献
Bavetsias; Skelton; Yafai; Mitchell; Wilson; Allan; Jackman
Journal of Medicinal Chemistry, 2002 , vol. 45, # 17 p. 3692 - 3702
反应条件
1: 94 percent / AcOH; conc. HCl / 24 h / 118 °C 2: 6.52 g / N-methylpyrrolidinone / 2 h / 163 °C 3: 93 percent / aq. KOH; H2O2 / 2 h / 130 °C 4: 97 percent / tetrahydrofuran / 6 h / 20 °C 5: 90 percent / DMAP / 3 h / 80 °C 6: 90 percent / pyridine / dimethylformamide / 2 h / 20 °C 7: 0.230 g / methanol; tetrahydrofuran / 26 h / 20 °C 8: 76 percent / 48percent aq. HBr / 7 h / 120 °C 9: 98 percent / DMAP; Et3N / CH2Cl2 / 0.5 h / 20 °C 10: 51 percent / NBS; dibenzoyl peroxide / CCl4 / 3.83 h / 85 °C / Irradiation 11: 73 percent / 2,6-lutidine / dimethylformamide / 5.5 h / 120 °C 12: 80 percent / aq. NaOH / tetrahydrofuran / 1 h / 20 °C 13: 94 percent / Et3N / CH2Cl2 / 0.92 h 14: 77 percent / CH2Cl2 / 2.5 h / 20 °C 15: 0.142 g / TFA / CH2Cl2 / 0.92 h / 20 °C 16: PyBOP; diisopropylethylamine / dimethylformamide / 3 h View Scheme
参考文献
Bavetsias; Skelton; Yafai; Mitchell; Wilson; Allan; Jackman
Journal of Medicinal Chemistry, 2002 , vol. 45, # 17 p. 3692 - 3702
反应条件
1: 97 percent / tetrahydrofuran / 6 h / 20 °C 2: 90 percent / DMAP / 3 h / 80 °C 3: 90 percent / pyridine / dimethylformamide / 2 h / 20 °C 4: 0.230 g / methanol; tetrahydrofuran / 26 h / 20 °C 5: 76 percent / 48percent aq. HBr / 7 h / 120 °C 6: 98 percent / DMAP; Et3N / CH2Cl2 / 0.5 h / 20 °C 7: 51 percent / NBS; dibenzoyl peroxide / CCl4 / 3.83 h / 85 °C / Irradiation 8: 73 percent / 2,6-lutidine / dimethylformamide / 5.5 h / 120 °C 9: 80 percent / aq. NaOH / tetrahydrofuran / 1 h / 20 °C 10: 94 percent / Et3N / CH2Cl2 / 0.92 h 11: 77 percent / CH2Cl2 / 2.5 h / 20 °C 12: 0.142 g / TFA / CH2Cl2 / 0.92 h / 20 °C 13: PyBOP; diisopropylethylamine / dimethylformamide / 3 h View Scheme
参考文献
Bavetsias; Skelton; Yafai; Mitchell; Wilson; Allan; Jackman
Journal of Medicinal Chemistry, 2002 , vol. 45, # 17 p. 3692 - 3702
反应条件
1: 93 percent / aq. KOH; H2O2 / 2 h / 130 °C 2: 97 percent / tetrahydrofuran / 6 h / 20 °C 3: 90 percent / DMAP / 3 h / 80 °C 4: 90 percent / pyridine / dimethylformamide / 2 h / 20 °C 5: 0.230 g / methanol; tetrahydrofuran / 26 h / 20 °C 6: 76 percent / 48percent aq. HBr / 7 h / 120 °C 7: 98 percent / DMAP; Et3N / CH2Cl2 / 0.5 h / 20 °C 8: 51 percent / NBS; dibenzoyl peroxide / CCl4 / 3.83 h / 85 °C / Irradiation 9: 73 percent / 2,6-lutidine / dimethylformamide / 5.5 h / 120 °C 10: 80 percent / aq. NaOH / tetrahydrofuran / 1 h / 20 °C 11: 94 percent / Et3N / CH2Cl2 / 0.92 h 12: 77 percent / CH2Cl2 / 2.5 h / 20 °C 13: 0.142 g / TFA / CH2Cl2 / 0.92 h / 20 °C 14: PyBOP; diisopropylethylamine / dimethylformamide / 3 h View Scheme
参考文献
Bavetsias; Skelton; Yafai; Mitchell; Wilson; Allan; Jackman
Journal of Medicinal Chemistry, 2002 , vol. 45, # 17 p. 3692 - 3702
反应条件
1: 90 percent / pyridine / dimethylformamide / 2 h / 20 °C 2: 0.230 g / methanol; tetrahydrofuran / 26 h / 20 °C 3: 76 percent / 48percent aq. HBr / 7 h / 120 °C 4: 98 percent / DMAP; Et3N / CH2Cl2 / 0.5 h / 20 °C 5: 51 percent / NBS; dibenzoyl peroxide / CCl4 / 3.83 h / 85 °C / Irradiation 6: 73 percent / 2,6-lutidine / dimethylformamide / 5.5 h / 120 °C 7: 80 percent / aq. NaOH / tetrahydrofuran / 1 h / 20 °C 8: 94 percent / Et3N / CH2Cl2 / 0.92 h 9: 77 percent / CH2Cl2 / 2.5 h / 20 °C 10: 0.142 g / TFA / CH2Cl2 / 0.92 h / 20 °C 11: PyBOP; diisopropylethylamine / dimethylformamide / 3 h View Scheme
参考文献
Bavetsias; Skelton; Yafai; Mitchell; Wilson; Allan; Jackman
Journal of Medicinal Chemistry, 2002 , vol. 45, # 17 p. 3692 - 3702
反应条件
1: 90 percent / DMAP / 3 h / 80 °C 2: 90 percent / pyridine / dimethylformamide / 2 h / 20 °C 3: 0.230 g / methanol; tetrahydrofuran / 26 h / 20 °C 4: 76 percent / 48percent aq. HBr / 7 h / 120 °C 5: 98 percent / DMAP; Et3N / CH2Cl2 / 0.5 h / 20 °C 6: 51 percent / NBS; dibenzoyl peroxide / CCl4 / 3.83 h / 85 °C / Irradiation 7: 73 percent / 2,6-lutidine / dimethylformamide / 5.5 h / 120 °C 8: 80 percent / aq. NaOH / tetrahydrofuran / 1 h / 20 °C 9: 94 percent / Et3N / CH2Cl2 / 0.92 h 10: 77 percent / CH2Cl2 / 2.5 h / 20 °C 11: 0.142 g / TFA / CH2Cl2 / 0.92 h / 20 °C 12: PyBOP; diisopropylethylamine / dimethylformamide / 3 h View Scheme
参考文献
Bavetsias; Skelton; Yafai; Mitchell; Wilson; Allan; Jackman
Journal of Medicinal Chemistry, 2002 , vol. 45, # 17 p. 3692 - 3702
反应条件
1: 0.230 g / methanol; tetrahydrofuran / 26 h / 20 °C 2: 76 percent / 48percent aq. HBr / 7 h / 120 °C 3: 98 percent / DMAP; Et3N / CH2Cl2 / 0.5 h / 20 °C 4: 51 percent / NBS; dibenzoyl peroxide / CCl4 / 3.83 h / 85 °C / Irradiation 5: 73 percent / 2,6-lutidine / dimethylformamide / 5.5 h / 120 °C 6: 80 percent / aq. NaOH / tetrahydrofuran / 1 h / 20 °C 7: 94 percent / Et3N / CH2Cl2 / 0.92 h 8: 77 percent / CH2Cl2 / 2.5 h / 20 °C 9: 0.142 g / TFA / CH2Cl2 / 0.92 h / 20 °C 10: PyBOP; diisopropylethylamine / dimethylformamide / 3 h View Scheme
参考文献
Bavetsias; Skelton; Yafai; Mitchell; Wilson; Allan; Jackman
Journal of Medicinal Chemistry, 2002 , vol. 45, # 17 p. 3692 - 3702
