* 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.
Phosphorus oxychloride (4 mL) and 1 drop of DMF were added to 4-bromoisophthalamide (868 mg, 3.6 mmol). The reaction was heated at 90 °C for 1.5 hrs, allowed to cool to rt, pipetted onto ice, and then stirred for 10 min.The solids were filtered, rinsed with water, and dried under high vacuum to give the title compound as a white solid (671 mg). 1H NMR (400MHz, DMSO-d6): ö 8.59-8.56 (m, 1H), 8.15-8.08 (m, 2H).
Reference:
[1] Journal of Materials Chemistry C, 2015, vol. 3, # 28, p. 7345 - 7355
[2] Journal of Organic Chemistry, 1970, vol. 35, p. 287 - 295
[3] Patent: WO2013/142266, 2013, A1, . Location in patent: Paragraph 00529
2
[ 820231-69-4 ]
[ 22433-89-2 ]
Yield
Reaction Conditions
Operation in experiment
82.1%
for 4.5 h; Heating / reflux
Placing Compound F in an amount of 42.0 g(118 mmol) and thionyl chloride in an amount of 285 milliliter into a flask, the resultant solution was reacted for 4.5 hours under refluxing. Distillating away an excess of thionyl chloride, a resultant yellow solid was washed with a use of ethyl acetate and toluene. After drying, 20.1 g of Intermediate G as white crystals was obtained (yield: 82.1 percent).
With N,N-dimethyl-formamide; trichlorophosphate; at 90℃; for 1.5h;
Phosphorus oxychloride (4 mL) and 1 drop of DMF were added to 4-bromoisophthalamide (868 mg, 3.6 mmol). The reaction was heated at 90 C for 1.5 hrs, allowed to cool to rt, pipetted onto ice, and then stirred for 10 min.The solids were filtered, rinsed with water, and dried under high vacuum to give the title compound as a white solid (671 mg). 1H NMR (400MHz, DMSO-d6): oe 8.59-8.56 (m, 1H), 8.15-8.08 (m, 2H).
Placing Compound F in an amount of 42.0 g(118 mmol) and thionyl chloride in an amount of 285 milliliter into a flask, the resultant solution was reacted for 4.5 hours under refluxing. Distillating away an excess of thionyl chloride, a resultant yellow solid was washed with a use of ethyl acetate and toluene. After drying, 20.1 g of Intermediate G as white crystals was obtained (yield: 82.1 %).
5-[3-(2,4-dicyanophenoxy)phenoxy]isophthalonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With potassium carbonate; In 1-methyl-pyrrolidin-2-one;
Example 6 A mixture of 5-(3-hydroxyphenoxy)isophthalonitrile (94 mg) and anhydrous potassium carbonate (55 mg) in 1-methyl-2-pyrrolidinone was stirred at 100 C. under a nitrogen atmosphere for 30 minutes then allowed to cool slightly. <strong>[22433-89-2]4-Bromoisophthalonitrile</strong> (124 mg) was added and the mixture heated at 100 C. for 1.5 hours. The cooled mixture was partitioned between ethyl acetate and water, the aqueous phase was extracted with ethyl acetate and the combined organic solution washed with aqueous sodium hydroxide (2M) and water. The ethyl acetate solution was dried (anhydrous magnesium sulphate) and concentrated and purified by dry column chromatography on silica (eluent dichloromethane/isohexane 2:1) to give 5-[3-(2,4-dicyanophenoxy)phenoxy]isophthalonitrile (Compound 59, 73 mg), NMR (D6 DMSO) 8.57 (1H, d); 8.26 (1H, t); 8.09 (1H, dd); 8.03 (2H, d); 7.60 (1H, t); 7.24-7.10 (3H, m).
Placing 2-bromopyridine in an amount of 83.7 g (530 mmol) and tetrahydrofuran (THF) in an amount of 83.7 g into a flask, a THF solution of 2.5M isopropyl magnesium chloride in an amount of 214 g (530 mmol) was dripped under cooling with ice, and the resultant solution was reacted at room temperature for 3 hours. Subsequently, Grignard agent prepared above was added into THF solution of anhydrous zinc bromide in an amount of 120.5 g (535 mmol), the resultant solution was further reacted for 2 hours at room temperature. Throwing Conpound G in an amount of 18.5 g (89.4 mmol) and Pd(PPh3)4 in an amount of 1.2 g (1.0 mmol) into the reacted solution, the resultant solution was further reacted at a temperature of 50C for 10 hours. After condensing the resultant reacted solution, it was extracted with the use of methylen chloride and a separated organic layer was washed several times with the use of water, followed by drying with the use of magnesium sulfate. After condensation, the resultant crystals were purified by means of a silica column chromatography (developing solution: toluene / ethyl acetate =10/1), and as a result, 8.28 g of Intermediate 1-5b as white crystals were obtained (yield: 45.2 %). It was confirmed in accordance with GC-MS that Intermediate 1-5b was the aimed compound. The measurement result is shown as follows: GC-MS: m/z=205
tert-butyl 6-(acetamidomethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindoline-2-carboxylate[ No CAS ]
tert-butyl 6-(acetamidomethyl)-4-(2,4-dicyanophenyl)isoindoline-2-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
0.12 g
With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; potassium carbonate; In 1,4-dioxane; water; at 85℃; for 4h;
Step b. To a stirred solution of tert-butyl 6-(acetamidomethyl)-4-(4,4,5,5-tetramethyl-l,3,2- dioxaborolan-2-yl)isoindoline-2-carboxylate (1.000 g, 2.415 mmol) in 1,4-dioxane: water (9: 1, 4.4 ml) were added K2C03 (0.330 g, 2.40 mmol) and <strong>[22433-89-2]4-bromoisophthalonitrile</strong> (CAS Number 22433-89-2; 0.250 g, 1.208 mmol) at rt. The reaction mixture was degassed for 20 min before addition of PdCl2(dppf) (0.080 g, 0.120 mmol). The resulting reaction mixture was heated at 85C for 4 h. The reaction mixture was cooled to rt, poured into water (100 ml) and extracted with EtOAc (3 x 100 ml). The combined organic phase dried over Na2S04, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography (70% EtOAc in hexane) yielding tert-butyl 6-(acetamidomethyl)-4-(2,4-dicyanophenyl)isoindoline-2-carboxylate (0.120 g, 0.288 mmol). LCMS: Method A, 1.853 min, MS: ES+ 361.58 [M-56].
2-(tert-butyl) 5-methyl 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindoline-2,5-dicarboxylate[ No CAS ]
2-(tert-butyl) 5-methyl 7-(2,4-dicyanophenyl)isoindoline-2,5-dicarboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
0.35 g
With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; sodium hydrogencarbonate; In water; N,N-dimethyl-formamide; at 90℃; for 4h;
Step b. To a stirred solution of 2-(tert-butyl) 5-methyl 7-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)isoindoline-2,5-dicarboxylate (0.500 g, 1.240 mmol) in DMF:water (9: 1, 15 ml) were added NaHC03 (0.260 g, 3.10 mmol) and <strong>[22433-89-2]4-bromoisophthalonitrile</strong> (CAS Number 22433-89-2; 0.214 g, 1.003 mmol) at rt. The reaction mixture was degassed for 20 min before addition of PdCl2(dppf) (0.075 g, 0.124 mmol). The resulting reaction mixture was heated at 90C for 4 h. The reaction mixture was cooled to rt, poured into water (50 ml) and extracted with EtOAc (3 x 15 ml). The combined organic phase dried over Na2S04, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography (40% EtOAc in hexane) yielding 2-(tert-butyl) 5-methyl 7-(2,4-dicyanophenyl)isoindoline-2,5-dicarboxylate (0.350 g, 0.868 mmol). LCMS: Method A, 2.299 min, MS: ES+ 421.70 [M+18].
2-(2,5-difluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane[ No CAS ]
[ 22433-89-2 ]
C14H6F2N2[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
16 g
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In water; toluene; at 100℃;Inert atmosphere;
At room temperature, 500 mL of toluene, 20 g of intermediate M1 (83.3 mmol, 1.2 eq), 14.3 g of <strong>[22433-89-2]4-bromoisophthalonitrile</strong> (70 mmol, 1 eq), sodium carbonate aqueous solution (sodium carbonate) 22.3 g, 210 mmol, 3 eq, 105 mL of water, 2 M), 4.04 g (3.5 mmol, 0.05 eq) of tetratriphenylphosphine palladium, started stirring, replaced nitrogen 3 times, warmed to 100 C., and reacted overnight. (PE: DCM = 20: 1, product Rf = 0.7, intermediate M1Rf = 0.2)The reaction solution was lowered to room temperature and extracted with ethyl acetate. The upper layer was taken and the reaction solution was spin-dried. PE: DCM = 30: 1 was passed through the column to obtain a white solid, 16 g of intermediate M1.
With copper(l) iodide; caesium carbonate; ethylenediamine; In 5,5-dimethyl-1,3-cyclohexadiene; for 24h;Inert atmosphere; Reflux;
Add 400 mL of xylene to a 1000 mL single-necked flask with magnetic stirring at room temperature.Compound M3 5 g (10 mmol, 1 eq), <strong>[22433-89-2]4-bromoisophthalonitrile</strong> 2.25 g (11 mmol, 1.1 eq),Cuprous iodide 3.57g (20mmol, 2eq), cesium carbonate 13g (40mmol, 4eq),1.16 g (20 mmol, 2 eq) of ethylenediamine was turned on and stirred, and nitrogen was replaced 3 times. The temperature was raised to reflux, and the reaction was carried out for 24 h.The reaction solution was cooled to room temperature, suction filtered, and the filtrate was spin-dried. DCM: AE = 1: 1 was passed through a silica gel column to obtain 4.5 g of an off-white solid.The product was washed with ethanol to remove impurities to obtain a crude product. The obtained crude product was then washed with toluene.Finally, 3.7 g of white solid P25 was obtained with a purity of 98.9%.