* 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.
Step A 3-Phenylamino-propionic acidA mixture of 3-phenylamino-propionitrile (5.03g, 34.4 mmol) in 60 ml_ of NaOH (10percent) solution is heated to reflux. After 1h, the mixture is cooled and acidified with acetic acid. The resulting solution is subsequently extracted with ethyl acetate and the combined extracts are washed by brine, and dried over anhydrous sodium sulfate. After concentration, the residue is purified by flash chromatography (methanol-dichloromethane), and gives the title compound (4.39 g, 77.7percent yield).
With platinum on activated charcoal; phenylsilane In toluene at 80℃; for 15 h; Schlenk technique; Inert atmosphere
An activated carbon supported platinum catalyst (Pt / C, 0.06 mg platinum, 0.0003 mmol, 0.1 molpercent) was added to a 10 mL Schlenk tube,After evacuation of argon, add 1 mL of solvent (toluene).Under argon protection, to the above system,Were successively added with phenylsilane (78.9 mg, 0.75 mmol), III-12 (R2 =Phenyl, R3 = 2-cyanoethyl) (43.9 mg, 0.3 mmol) and formic acid (27.6 mg, 0.6 mmol). The whole antiThe reaction was carried out at 80 ° C with stirring for 15 hours.After completion of the reaction, 3 mL of ethyl acetate was added to the system,The reaction was quenched with aqueous sodium hydroxide (3 mol / L, 3 mL)Ethyl acetate (3 x 10 mL), the organic phase was separated,Dried over anhydrous Na2SO4, filtered,The solvent was removed by rotary evaporation.The residue was purified by column chromatography on ethyl acetate / petroleum ether = 1: 50 mixed solvent,Separation and purification gave the title product IV-1226.4 mg, yield 55percent.
Reference:
[1] Angewandte Chemie - International Edition, 2015, vol. 54, # 31, p. 9042 - 9046[2] Angew. Chem., 2015, vol. 127, # 31, p. 9170 - 9174,5
[3] Catalysis Science and Technology, 2016, vol. 6, # 16, p. 6172 - 6176
[4] Patent: CN106892826, 2017, A, . Location in patent: Paragraph 0165; 0166; 0167; 0168; 0169; 0170
[5] Chemistry - A European Journal, 2014, vol. 20, # 26, p. 7879 - 7883
3
[ 1075-76-9 ]
[ 75-05-8 ]
[ 94-34-8 ]
Yield
Reaction Conditions
Operation in experiment
93%
at 80℃; for 24 h; Inert atmosphere; Schlenk technique; Glovebox
1) Under the protection of nitrogen,In a glove box 0.5 mmol of 3- (anilino) propionitrile, 8 equiv PMHS (4 mmol Si-H),2.5 molpercent potassium phosphate,5 molpercent 18-crown-6, 3.2 ml acetonitrile were added to a 100 ml schlenk tube.2) The N2 in the schlenk tube is replaced with CO2 as the C1 source by means of a double-tube tube in a liquid nitrogen-cooled freeze-plow operation and the CO2 pressure is 1 bar.3) The reaction was carried out at 80 ° C for 24 hours.4) After the reaction was separated by column chromatography,The stationary phase was silica gel, the mobile phase was petroleum ether and ethyl acetate, and the volume ratio was 9: 1.Bruker nuclear magnetic resonance, the final target productN-methyl-N-cyanoethylaniline (shown in Figures 3 and 4),Isolated yield 93percent.
Reference:
[1] Patent: CN107337606, 2017, A, . Location in patent: Paragraph 0055; 0056; 0057; 0058; 0059; 0060
Stage #1: N-cyanoethylaniline With acetic acid at 120℃; for 1h; Inert atmosphere; Autoclave;
Stage #2: oxirane at 95℃; for 2h; Inert atmosphere;
1.1; 2.1; 3.1; 4.1; 5.1 Example 3
(1) Replace the air in the autoclave with nitrogen. After three consecutive replacements, add 100 g of N-cyanoethyl aniline and 15 g of 98% acetic acid to the autoclave, start stirring, and heat to 120°C and keep it for 1 hour. , So that N-cyanoethyl aniline completely dissolves. After the N-cyanoethyl aniline is completely dissolved, 35g of ethylene oxide is introduced. During the introduction, the temperature is controlled at 95°C and the pressure is maintained at ≤0.3MPa. After the passing is completed, the hydroxyl compound N- is obtained after the reaction is maintained at 95°C for 2 hours. Cyanoethyl-N-hydroxyethyl aniline; after the reaction, the temperature of the hydroxyl compound N-cyanoethyl-N-hydroxyethyl aniline is about 95°C.
2,4-diamino-5-(4-amino-3,5-dimethyl-benzl)-pyrimidine[ No CAS ]
[ 56066-79-6 ]
Yield
Reaction Conditions
Operation in experiment
With sodium methylate In water; dimethyl sulfoxide; ethyl acetate
23 Preparation of 2,4-diamino-5-(4-amino-3,5-dimethyl-benzl)-pyrimidine
A mixture of 1.38 g. of sodium methylate and 3.8 g. of 4-amino-3,5-dimethyl-benzaldehyde in 30 ml. of absolute dimethylsulfoxide was treated under an atmosphere of nitrogen for 10 minutes with a solution of 3.72 g. of β-anilino-propionitrile in 30 ml. of absolute dimethylsulfoxide with stirring at 55° C. and then stirred for 1 hour at 70° C. The solution was poured into 1 liter of water. The resulting emulsion was extracted with two 500 ml. portions of ethyl acetate. The ethyl acetate extract was washed with two 300 ml. portions of water, dried over magnesium sulfate and evaporated to dryness under vacuum. After recrystallization of the residue from ethyl acetate, there was obtained 4-amino-α-(anilino-methylene)-3,5-dimethyl-hydrocinnamic acid nitrile having a m.p. of 165°-167° C.
With dipotassium hydrogenphosphate; 18-crown-6 ether; In tetrahydrofuran; at 80℃; for 12h;Molecular sieve;
General procedure: In air, K2HPO4 (10 mol %, 4.35mg), PMHS (242 mul), amine (0.25 mmol), formic acid (4.6equiv ,43.3mul), 18-crown-6 (20mol %, 13.2mg) 4A MS(10mg) and 2 ml THF were added into a tube equipped with a water condenser. The reaction mixturewas stirred at 80C for 12 hours. The yields of isolated products were reported. The mixture was filtered through a silica gelcolumn with petroleum ether and ethyl acetate as the eluent. The resultant solution was concentrated and purified by silica gelcolumn chromatography to give the corresponding product.
55%
With platinum on activated charcoal; phenylsilane; In toluene; at 80℃; for 15h;Schlenk technique; Inert atmosphere;
An activated carbon supported platinum catalyst (Pt / C, 0.06 mg platinum, 0.0003 mmol, 0.1 mol%) was added to a 10 mL Schlenk tube,After evacuation of argon, add 1 mL of solvent (toluene).Under argon protection, to the above system,Were successively added with phenylsilane (78.9 mg, 0.75 mmol), III-12 (R2 =Phenyl, R3 = 2-cyanoethyl) (43.9 mg, 0.3 mmol) and formic acid (27.6 mg, 0.6 mmol). The whole antiThe reaction was carried out at 80 C with stirring for 15 hours.After completion of the reaction, 3 mL of ethyl acetate was added to the system,The reaction was quenched with aqueous sodium hydroxide (3 mol / L, 3 mL)Ethyl acetate (3 x 10 mL), the organic phase was separated,Dried over anhydrous Na2SO4, filtered,The solvent was removed by rotary evaporation.The residue was purified by column chromatography on ethyl acetate / petroleum ether = 1: 50 mixed solvent,Separation and purification gave the title product IV-1226.4 mg, yield 55%.
With 18-crown-6 ether; carbon dioxide; at 80℃; under 750.075 Torr; for 24h;Inert atmosphere; Schlenk technique; Glovebox;
1) Under the protection of nitrogen,In a glove box 0.5 mmol of 3- (anilino) propionitrile, 8 equiv PMHS (4 mmol Si-H),2.5 mol% potassium phosphate,5 mol% 18-crown-6, 3.2 ml acetonitrile were added to a 100 ml schlenk tube.2) The N2 in the schlenk tube is replaced with CO2 as the C1 source by means of a double-tube tube in a liquid nitrogen-cooled freeze-plow operation and the CO2 pressure is 1 bar.3) The reaction was carried out at 80 C for 24 hours.4) After the reaction was separated by column chromatography,The stationary phase was silica gel, the mobile phase was petroleum ether and ethyl acetate, and the volume ratio was 9: 1.Bruker nuclear magnetic resonance, the final target productN-methyl-N-cyanoethylaniline (shown in Figures 3 and 4),Isolated yield 93%.
3-(isoquinolin-1-yl(phenyl)amino)propanenitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
94%
With 1,4-diaza-bicyclo[2.2.2]octane; 1,3-dicyano-5-fluoro-2,4,6-tris(diphenylamino)benzene In acetonitrile at 20℃; for 12h; Inert atmosphere; Irradiation;