N-(2-Aminophenyl)-4-([[4-(pyridin-3-yl)pyrimidin-2-yl]amino]methyl)benzamide synthesis
- Product Name:N-(2-Aminophenyl)-4-([[4-(pyridin-3-yl)pyrimidin-2-yl]amino]methyl)benzamide
- CAS Number:726169-73-9
- Molecular formula:C23H20N6O
- Molecular Weight:396.44
![4-({[4-(Pyridin-3-yl)pyrimidin-2-yl]amino}methyl)benzoic acid](/CAS/GIF/849235-68-3.gif)
849235-68-3
95-54-5
726169-73-9
To a 2L three-necked round-bottomed flask equipped with a thermometer, a nitrogen introduction tube, a mechanical stirrer, and a dropping funnel was added 4-(((4-(pyridin-3-yl)pyrimidin-2-yl)amino)methyl)benzoic acid (3.40 g, 0.131 mol), o-phenylenediamine (59.3 g, 0.548 mol), 1-hydroxybenzotriazole hydrate (HOBT) (21.7 g 0.156 mol) and DMSO (240 mL). Triethylamine (Et3N) (43.7 mL, 0.313 mol) was added to the stirring mixture at room temperature. The reaction mixture was stirred for 10 minutes, then a suspension of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC-HCl) (30.04 g, 0.156 mol) in DMSO (240 mL) was added in batches of three over 30 minutes at the same temperature. After addition, the reaction mixture was continued to be stirred for 20 h. (The progress of the reaction was monitored by NMR or HPLC to confirm complete consumption of 4-(((4-(pyridin-3-yl)pyrimidin-2-yl)amino)methyl)benzoic acid). Upon completion of the reaction, 30% isopropanol (IPA) aqueous solution (800 mL) was added to the reaction mixture in three portions over 30 minutes. After addition, the reaction mixture formed a suspension, which was cooled to 0-5°C over 45 minutes and stirring was continued at the same temperature for 1 hour. The solid product was collected by diafiltration, washed with 30% aqueous IPA (400 mL) and dried over air to afford the crude product N-(2-aminophenyl)-4-(((4-(pyridin-3-yl)pyrimidin-2-yl)amino)methyl)benzamide (43.04 g, 83% yield).
849235-68-3
13 suppliers
$548.00/500mg
95-54-5
536 suppliers
$9.00/1g
726169-73-9
171 suppliers
$28.00/1unit
Yield: 83%
Reaction Conditions:
with benzotriazol-1-ol;1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride;triethylamine in dimethyl sulfoxide at 20; for 20.6 h;Solvent;
Steps:
6 N-(2-Aminophenyl)-4-((4-(pyridin-3 .-yl)pyrirnidin-2-ylarnino)methyl)benzamide (4)
A 2L, three-neck round bottom flask equipped with a thermometer, nitrogen inlet, a mechanical stirrer and a dropping funnel was charged with 4-((4-(pyridin-3-yl)pyrirnidin-2- ylarnino)rnethyl)benzoic acid (3, 40 g, 0.131 mol), 1,2-phenylenediamine (59.3 g, 0.548 mol), 1- hydroxybenzotriazole hydrate (HOBT) (21.7 g, 0.156 mol) and DMSO (240 rnL) at roomtemperature. To this stirred mixture Et3N (43.7 mL, 0.313 mol) was added. The reaction mixture was stirred for 10 mm then was charged with a suspension of 1-(3-dimethylarninopropyl)-3- ethylcarbodiirnide hydrochloride (EDC x HC1) (30.04 g, 0.156 mol)) in DMSO (240 rnL) at the same temperature. The addition occurred in three equal portions over 30 mm.[0275] The reaction mixture was then stirred for 20 hours (the progress of the reaction was monitored by NMR or HPLC for the disappearance of the acid 3). Upon completion of the reaction 30% IPA in water (800 mL) was added to the reaction mixture in three portions over 30 mm. After complete addition the reaction mixture turned into a suspension which was cooled to 0-5°C over 45 mm and then stirred at the same temperature for another hour. The solid material was collected by a suction filtration, washed with 30% IPA (400 rnL) and air-dried to afford crude title compound 4 (43.04 g, 83% yield).
References:
METHYLGENE INC.;RAEPPEL, Stephane;ZHOU, Zhihong;GAUDETTE, Frederic;LLEWELLYN, David;VAISBURG, Arkadii;DELORME, David;RAEPPEL, Franck;GRANGER, Marie-Claude;ROY, Simon WO2015/6875, 2015, A1 Location in patent:Paragraph 0274; 0275
849235-67-2
19 suppliers
$548.00/500mg
726169-73-9
171 suppliers
$28.00/1unit
736080-30-1
15 suppliers
$352.00/500 mg
726169-73-9
171 suppliers
$28.00/1unit
350-03-8
657 suppliers
$10.00/5g
726169-73-9
171 suppliers
$28.00/1unit