* 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 N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 2 h;
General procedure: Acryloyl chloride (60 µL, 0.68 mmol) was added dropwise to a solution of amine 4, 14 or 25 (300 mg, 0.68 mmol) and diisopropyethylamine (120 µL, 0.68 mmol) in dichloromethane (10 mL) at 0 °C. The reaction was stirred for 2 h. Then water (10 mL) was added to the reaction mixture and extracted three times with dichloromethane (3 x 6 mL). The combined organic extracts was dried over anhydrous sodium sulfate and concentrated to give a pale white solid. The crude product was purified by flash column chromatography using dichloromethane-methanol (98:2) to obtain the pure acrylamide 1, 2 or 23 as white solids in yields ranging from 31 - 36percent.
Reference:
[1] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 21, p. 4832 - 4837
[2] Patent: WO2010/129053, 2010, A2, . Location in patent: Page/Page column 124-125
[3] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 2, p. 638 - 643
[4] European Journal of Medicinal Chemistry, 2014, vol. 77, p. 75 - 83
2
[ 122833-04-9 ]
[ 1213269-23-8 ]
Reference:
[1] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 2, p. 638 - 643
[2] European Journal of Medicinal Chemistry, 2014, vol. 77, p. 75 - 83
[3] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 21, p. 4832 - 4837
3
[ 76661-24-0 ]
[ 1213269-23-8 ]
Reference:
[1] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 2, p. 638 - 643
[2] European Journal of Medicinal Chemistry, 2014, vol. 77, p. 75 - 83
[3] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 21, p. 4832 - 4837
4
[ 554-84-7 ]
[ 1213269-23-8 ]
Reference:
[1] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 2, p. 638 - 643
[2] European Journal of Medicinal Chemistry, 2014, vol. 77, p. 75 - 83
[3] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 21, p. 4832 - 4837
5
[ 1213269-25-0 ]
[ 1213269-23-8 ]
Reference:
[1] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 2, p. 638 - 643
[2] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 21, p. 4832 - 4837
6
[ 448-19-1 ]
[ 1213269-23-8 ]
Reference:
[1] European Journal of Medicinal Chemistry, 2014, vol. 77, p. 75 - 83
[2] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 21, p. 4832 - 4837
7
[ 446-36-6 ]
[ 1213269-23-8 ]
Reference:
[1] European Journal of Medicinal Chemistry, 2014, vol. 77, p. 75 - 83
8
[ 109-01-3 ]
[ 1213269-23-8 ]
Reference:
[1] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 21, p. 4832 - 4837
With N-ethyl-N,N-diisopropylamine; In dichloromethane; for 2.0h;
General procedure: Acryloyl chloride (60 muL, 0.68 mmol) was added dropwise to a solution of amine 4, 14 or 25 (300 mg, 0.68 mmol) and diisopropyethylamine (120 muL, 0.68 mmol) in dichloromethane (10 mL) at 0 C. The reaction was stirred for 2 h. Then water (10 mL) was added to the reaction mixture and extracted three times with dichloromethane (3 x 6 mL). The combined organic extracts was dried over anhydrous sodium sulfate and concentrated to give a pale white solid. The crude product was purified by flash column chromatography using dichloromethane-methanol (98:2) to obtain the pure acrylamide 1, 2 or 23 as white solids in yields ranging from 31 - 36%.
With N-ethyl-N,N-diisopropylamine; In dichloromethane; for 1.0h;
N-(3-(5-chloro-2-(2-methoxy-4-(4-methylpiperazin-l-yl)phenyIamino)pyrimidin-4- yloxy)phenyl)acrylamide Acryloyl chloride (0.257 mL, 3.18 mmol) was added dropwise to a solution of 4-(3-aminophenoxy)-5-chloro-N-(2-methoxy-4-(4-methylpiperazin-l- yl)phenyl)- pyrimidin-2-amine (1.40 g, 3.18 mmol) and diisopropyethylamine (0.56 mL, 3.18 mmol) in methylene chloride (30 mL) at 0 0C. The reaction was stirred for Ih. 1.10 g of the title compound was obtained after purification by flash chromatography with 20: 1 (v/v) dichloromethane -methanol. 1H NMR 600 MHz (DMSO-d6) delta 8.32 (s, I H), 7.38 (m, 2H), 7.26 (m, 2H), 6.96 (m, I H), 6.48 (m, 2H), 6.35 (dd, J=I 0.2 Hz, 17.4 Hz, I H), 6.21 (m, IH), 5.75 (d, J=9.6 Hz, IH), 3.80 (s, 3H), 3.61 (m, 4H), 3.1 1 (m, 4H), 2.38 (s, 3H); MS m/z: 495.97 (M+1).
General procedure: Compound 1 was dissolved in MeOH/THF (5/30 mL), and the required amine base (2-3.6 equiv) was added. The mixture was heated under reflux for 4h prior to the solvent being removed, 5% NH3 (aq) (50 mL) was added and the mixture was extracted with CH2Cl2 (50×3 mL). The organic layers were collected, washed with brine and dried over anhydrous sodium sulfate. After removal all solvent, the residue was purified using flash chromatography with dichloromethane- methanol- triethylamine to obtain the target compounds.
General procedure: Compound 1 was dissolved in MeOH/THF (5/30 mL), and the required amine base (2-3.6 equiv) was added. The mixture was heated under reflux for 4h prior to the solvent being removed, 5% NH3 (aq) (50 mL) was added and the mixture was extracted with CH2Cl2 (50×3 mL). The organic layers were collected, washed with brine and dried over anhydrous sodium sulfate. After removal all solvent, the residue was purified using flash chromatography with dichloromethane- methanol- triethylamine to obtain the target compounds.
General procedure: Compound 1 was dissolved in MeOH/THF (5/30 mL), and the required amine base (2-3.6 equiv) was added. The mixture was heated under reflux for 4h prior to the solvent being removed, 5% NH3 (aq) (50 mL) was added and the mixture was extracted with CH2Cl2 (50×3 mL). The organic layers were collected, washed with brine and dried over anhydrous sodium sulfate. After removal all solvent, the residue was purified using flash chromatography with dichloromethane- methanol- triethylamine to obtain the target compounds.
General procedure: Compound 1 was dissolved in MeOH/THF (5/30 mL), and the required amine base (2-3.6 equiv) was added. The mixture was heated under reflux for 4h prior to the solvent being removed, 5% NH3 (aq) (50 mL) was added and the mixture was extracted with CH2Cl2 (50×3 mL). The organic layers were collected, washed with brine and dried over anhydrous sodium sulfate. After removal all solvent, the residue was purified using flash chromatography with dichloromethane- methanol- triethylamine to obtain the target compounds.
General procedure: Compound 1 was dissolved in MeOH/THF (5/30 mL), and the required amine base (2-3.6 equiv) was added. The mixture was heated under reflux for 4h prior to the solvent being removed, 5% NH3 (aq) (50 mL) was added and the mixture was extracted with CH2Cl2 (50×3 mL). The organic layers were collected, washed with brine and dried over anhydrous sodium sulfate. After removal all solvent, the residue was purified using flash chromatography with dichloromethane- methanol- triethylamine to obtain the target compounds.
General procedure: Compound 1 was dissolved in MeOH/THF (5/30 mL), and the required amine base (2-3.6 equiv) was added. The mixture was heated under reflux for 4h prior to the solvent being removed, 5% NH3 (aq) (50 mL) was added and the mixture was extracted with CH2Cl2 (50×3 mL). The organic layers were collected, washed with brine and dried over anhydrous sodium sulfate. After removal all solvent, the residue was purified using flash chromatography with dichloromethane- methanol- triethylamine to obtain the target compounds.
General procedure: Compound 1 was dissolved in MeOH/THF (5/30 mL), and the required amine base (2-3.6 equiv) was added. The mixture was heated under reflux for 4h prior to the solvent being removed, 5% NH3 (aq) (50 mL) was added and the mixture was extracted with CH2Cl2 (50×3 mL). The organic layers were collected, washed with brine and dried over anhydrous sodium sulfate. After removal all solvent, the residue was purified using flash chromatography with dichloromethane- methanol- triethylamine to obtain the target compounds.
General procedure: Compound 1 was dissolved in MeOH/THF (5/30 mL), and the required amine base (2-3.6 equiv) was added. The mixture was heated under reflux for 4h prior to the solvent being removed, 5% NH3 (aq) (50 mL) was added and the mixture was extracted with CH2Cl2 (50×3 mL). The organic layers were collected, washed with brine and dried over anhydrous sodium sulfate. After removal all solvent, the residue was purified using flash chromatography with dichloromethane- methanol- triethylamine to obtain the target compounds.
General procedure: Compound 1 was dissolved in MeOH/THF (5/30 mL), and the required amine base (2-3.6 equiv) was added. The mixture was heated under reflux for 4h prior to the solvent being removed, 5% NH3 (aq) (50 mL) was added and the mixture was extracted with CH2Cl2 (50×3 mL). The organic layers were collected, washed with brine and dried over anhydrous sodium sulfate. After removal all solvent, the residue was purified using flash chromatography with dichloromethane- methanol- triethylamine to obtain the target compounds.