Category: 391211-97-5

Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 391211-97-5, name is 3,4-Difluoro-2-((2-fluoro-4-iodophenyl)amino)benzoic acid, This compound has unique chemical properties. The synthetic route is as follows., Application In Synthesis of 3,4-Difluoro-2-((2-fluoro-4-iodophenyl)amino)benzoic acid

EXAMPLE 6 1-F3, 4-DIFLUORO-2- (2-FLUORO-4-VINVIPHENYLAMINO)-PHENVLL-2-HYDROXV-ETHANONE Step A: Synthesis of R3, 4-DIFLUORO-2- (2-FLUORO-4-IODOD-PHENYLAMINO)-PHENVLL- methanol. To 3, 4-DIFLUORO-2-(2-FLUORO-4-IODO-PHENYLAMINO)-BENZOIC acid (10. 0g, 25. 4MMOL) in tetrahydrofuran was added, borane in tetrahydrofuran (38.2mL of a 1. OM solution) after 16 hours stirring at room temperature, the reaction was complete and quenched by careful addition of 2% HCI (100ML). The mixture was stirred for 1 H, brine was added and the organic layer was separated which was dried and evaporated to give a colorless solid (7. 13g 74%) that was recrystalized from hot dichloromethane/hexane to give an analytical sample. MS (APCI+) 380 (M+1+) ; H NMR (400mHz, DMSO) 7.62 (s, 1H), 7.50 (d, 1H), 7.24 (m, 3H), 6.29 (d of t, 1 H), 5.35 (t, 1 H), 4.42 (d, 1 H).

According to the analysis of related databases, 391211-97-5, the application of this compound in the production field has become more and more popular.

Electric Literature of 391211-97-5, These common heterocyclic compound, 391211-97-5, name is 3,4-Difluoro-2-((2-fluoro-4-iodophenyl)amino)benzoic acid, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

In an oven-dried three-neck, 2 L flask was taken 3, 4-DUFLUORO-2- [ (2- fluoro-4-iodophenyl) amino] benzoic acid (196.7g, 0.5 moles) and DMF (900 mL). To this stirred solution was added pyridine (44.4 mL, 43.5g, 0.55 moles) at RT, and then pentafluorophenyl trifluoroacetate (95 mL, 154g, 0.55 moles) was added dropwise within 30 minutes. The mixture was stirred at RT for 20 hours. The mixture was diluted with hexanes-diethyl ether (1 : 1, v/v, 3L) and washed successively with water (2x2L), 1M HC1 (2x2L), saturated NAHCO3 solution (2x2L) and finally with water (2x2L). The organic layer was dried and concentrated under reduced pressure to afford 2,3, 4,5, 6-pentafluorophenyl-3,4- difluoro-2- [ (2-fluoro-4-iodophenyl) amino] benzoate as a red oil (92.3%, 258.5g).

The synthetic route of 391211-97-5 has been constantly updated, and we look forward to future research findings.

Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 391211-97-5, name is 3,4-Difluoro-2-((2-fluoro-4-iodophenyl)amino)benzoic acid, A new synthetic method of this compound is introduced below., Safety of 3,4-Difluoro-2-((2-fluoro-4-iodophenyl)amino)benzoic acid

To a stirred mixture of 3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino] benzoic acid (12 g, 30.5 mmol), prepared using procedures similar to those described in US 7,019,033, in dichloromethane (70 mL) at 0 C was added pyridine (2.5 mL, 30.8 mmol) followed by dropwise addition of cyanuric fluoride (2.8 mL, 33.6 mmol). The reaction mixture was stirred at 0 C for 10 minutes and then warmed to room temperature and stirred for 2 hours. The reaction mixture was diluted with water and extracted with dichloromethane (100 mL). The aqueous layer was extracted once with dichloromethane (50 mL). The combined organic layers were washed with saturated aqueous sodium bicarbonate solution, brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give crude product as a brownish solid. Crude product was purified by flash chromatography (plug, 25% ethyl acetate in hexanes) to afford 3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino] benzoyl fluoride as a beige solid (11.8 g, 97% yield). 1H NMR (400MHz, CD3OD): 8.41 (s, IH), 7.80-7.81 (m, IH), 7.52 (dd, IH), 7.43-7.47 (m, IH), 6.96-7.03 (m, IH), 6.85-6.92 (m, IH).

The synthetic route of 391211-97-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; EXELIXIS, INC.; WO2008/76415; (2008); A1;,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com

These common heterocyclic compound, 391211-97-5, name is 3,4-Difluoro-2-((2-fluoro-4-iodophenyl)amino)benzoic acid, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. Recommanded Product: 391211-97-5

To a flask containing 3, 4-difluoro-2- (2-fluoro-4-iodo-phenylamino)-benzoic acid (2.6 Kg, 6.6 mol) and N, N’-carbonyldiimidazole (1.1 Kg, 6.8 mol) under nitrogen atmosphere, was added 12 L of dry acetonitrile. After stirring at 22 5C for about 90 minutes, a solution of (R)-O- (2, 2-dimethyl- [1, 3] dioxolan-4-ylmethyl)-hydroxylamine in toluene was added (8.5 L total volume, about 8 moles of amine). The solution was stirred for at least 6 hours at 22 5 C. Aqueous hydrochloric acid (9 L, 1.5 molar) was added, and after stirring for about 5 minutes, the layers were separated. Aqueous hydrochloric acid (9 L, 1.5 molar) was added to the remaining top layer, and after stirring for about 20 hours, the layers were separated. The remaining top layer was concentrated by vacuum distillation, and then diluted with 15 L toluene and 2 L ethanol. The mixture was warmed to 35-45C and diluted with 20 L warm water, then cooled to 0-5C. The product was collected by filtration and washed with 2 L toluene. The product was recrystallized by dissolving in 12 L toluene and 2 L ethanol (50 5 C), adding 10 L water and cooling to 0-5C. After collecting the product by filtration and washing with toluene, the product was dried in a vacuum oven resulting in 2.6 Kg of N-[(R)- 2,3-Dihydroxypropoxy]-3, 4-difluoro-2- (2-fluoro-4-iodo-phenylamino)-benzamide. 2.4 Kg of the above compound as a mixture of different crystalline forms was stirred in a mixture of 10 L water and 1 L ethanol at 35+ 5C for 20-30 hours, then cooled to 25+ 5C. The product was collected by filtration and washed with 1 L of water, then dried in a vacuum oven at 65C. This resulted in 2.3 Kg of material which was greater than 90% form IV. Note: DSC analysis shows an onset of melting at 110C with only a small amount of the peak with an onset of melting at 117C.

The synthetic route of 3,4-Difluoro-2-((2-fluoro-4-iodophenyl)amino)benzoic acid has been constantly updated, and we look forward to future research findings.

Reference:
Patent; WARNER-LAMBERT COMPANY LLC; WO2005/46665; (2005); A1;,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com

Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 391211-97-5, name is 3,4-Difluoro-2-((2-fluoro-4-iodophenyl)amino)benzoic acid, A new synthetic method of this compound is introduced below., Recommanded Product: 391211-97-5

EXAMPLE 50A N-[(S)-2,3-Dihydroxy-propoxy]-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide (Form II of Compound C) Prepared from (S)-O-(2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-hydroxylamine and 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzoic acid by the alternative procedure described above for N-[(R)-2,3-Dihydroxy-propoxy]-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide: m.p. 118-119 C.

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Patent; Barrett, Stephen Douglas; Biwersi, Cathlin Marie; Chen, Michael Huai Gu; Kaufman, Michael David; Tecle, Haile; Warmus, Joseph Scott; US2004/54172; (2004); A1;,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com

Application of 391211-97-5,Some common heterocyclic compound, 391211-97-5, name is 3,4-Difluoro-2-((2-fluoro-4-iodophenyl)amino)benzoic acid, molecular formula is C13H7F3INO2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

Example 4. Preparation of N-((R)-2.3-dihydroxypropoxyV3.4-difluoro-2-(2-fluoro-4-iodo-phenylanriotainoV benzamide (Compound ) To a stirring solution of 3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-benzoic acid (9) (120 g, 0.30 mol) in a mixture of 1 mL N,N-dimethylformamide and 1000 mL toluene was added thionyl chloride (55 g, 0.462 mol). The mixture was heated to 50-65 C and stirred for 2 hours or until reaction completion as determined by HPLC (Conditions E). The final reaction mixture was then cooled and concentrated under reduced pressure to a slurry keeping the temperature below 35C. Toluene (600 mL) was added to dissolve the slurry and vacuum distillation was repeated. Additional toluene (600 mL) was added to the slurry dissolving all solids and the solution was then cooled to 5 -10C. The solution was then treated with O-{[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}hydroxylamine (6) (63 g, 0.43 mol) solution in 207 mL toluene followed by potassium carbonate (65 g) and water (200 mL), stirred for at least 2 hours at 20- 25C. The stirring was stopped to allow phase separation and the bottom phase was discarded. The remaining organic layer was treated with hydrochloric acid solution (7.4%, 240 mL) until pH was less than 1 and stirred for 2 hours. The final reaction mixture was slightly concentrated under vacuum collecting about 100 mL distillate and the resulting organic solution was cooled to 5C to crystallize the product and filtered. The filter cake was washed with toluene (1000 mL) followed by water (100 mL) and the wet cake (crude product Compound I) was charged back to the flask. Toluene (100 mL), ethanol (100 mL) and water (100 mL) are then added, stirred at 30-35C for about 15 min, and the bottom aqueous phase was discarded. Water (200 mL) was then added to the organic solution and the mixture was stirred at about 3O C to allow for crystallization. The stirring was continued for 2 hours after product crystallized, then it was further cooled to about 0C and stirred for at least 2 hours. The slurry was filtered and wet cake was dried under reduced pressure at 55-85C to yield the final product N-((R)-2,3-dihydroxypropoxy)-3,4- difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide (Compound I) product. Overall chemical yield was 86 g, 58%.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3,4-Difluoro-2-((2-fluoro-4-iodophenyl)amino)benzoic acid, its application will become more common.

Reference:
Patent; WARNER-LAMBERT COMPANY LLC; WO2006/134469; (2006); A1;,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com

Adding a certain compound to certain chemical reactions, such as: 391211-97-5, name is 3,4-Difluoro-2-((2-fluoro-4-iodophenyl)amino)benzoic acid, belongs to iodides-buliding-blocks compound, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound 391211-97-5, COA of Formula: C13H7F3INO2

Palladium hydroxide (100 mg) was suspended in a solution of l-(diphenylmethyl)-3-(2-hydroxyethyl)azetidin-3-ol (228 mg, 0.80 mmol) in methanol (15 mL), and the mixture was subjected to an atmosphere of hydrogen at 50 psi for 4 h. The catalyst was then removed by filtration through celite, and the filtrate was concentrated in vacuo to provide 3-(2-hydroxyethyl)azetidin-3-ol. This material was used in the subsequent reaction without purification. To a solution of 3,4- difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzoic acid (314 mg, 0.80 mmol), prepared using procedures similar to those described in US 7,019,033, in DMF (4 mL) was added PyBOP (416 mg, 0.80 mmol) and triethylamine (223 muL, 1.6 mmol). Finally, the unpurified 3-(2-hydroxyethyl)azetidin-3-ol was added, and the resulting mixture was stirred at rt for 16 h. Water and ethyl acetate were added, and the layers were separated. The aqueous phase was extracted with once more with ethyl acetate. The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash chromatography, eluting with ethyl acetate, to provide l-({3,4-difluoro-2-[(2-fluoro- 4-iodophenyl)amino]phenyl}carbonyl)-3-(2-hydroxyethyl)azetidin-3-ol as a colorless oil (303 mg, 0.62 mmol, 78% yield). 1H NMR (400 MHz, CDCl3): delta 8.46 (s, IH), 7.39 (dd, IH), 7.32 (m, IH), 7.13 (m, IH), 6.81 (m, IH), 6.60 (m, IH), 4.37 (br s, IH), 4.28 (br m, 4H), 3.94 (br s, 2H), 2.19 (br s, IH), 2.02 (m, 2H); MS (EI) for Ci8H16F3IN2O3: 491 (MH’).

In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles, 3,4-Difluoro-2-((2-fluoro-4-iodophenyl)amino)benzoic acid, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; EXELIXIS, INC.; WO2008/76415; (2008); A1;,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com

Related Products of 391211-97-5,Some common heterocyclic compound, 391211-97-5, name is 3,4-Difluoro-2-((2-fluoro-4-iodophenyl)amino)benzoic acid, molecular formula is C13H7F3INO2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

EXAMPLE 1 1-3. 4-DIFLUORO-2- (2-FLUORO-4-IODO-PHENVLAMINO)-PHENVLL-2-HYDROXV-ETHANONE To a stirring suspension comprised of 3, 4-DIFLUORO-2- (2-FLUORO-4-IODO-PHENYLAMINO)- benzoic acid (1.33 g, 3.4 MMOL, which can be prepared according to the procedure of WO 02/06213) and oxalyl chloride (1.4 mL, 16 mmoles) in dichloromethane (10 mL) at ambient temperature was added 0.025 mL OF N, N-DIMETHYLFORMAMIDE. The reaction mixture was stirred for ten minutes and was concentrated in vacuo to the yellow solid 3, 4-DIFLUORO-2- (2- FLUORO-4-IODO-PHENYLAMINO)-BENZOYL chloride. The yellow solid was suspended in tris (trimethylsiloxy) ethylene (10 g, 33 MMOL) and the stirring mixture was brought to 90 C under a nitrogen atmosphere for six hours. The mixture was cooled slightly, and to it was added a solution consisting of dioxane (25 mL) and 10% aqueous hydrochloric acid (10 mL). Vigorous liberation of gas ensued and the mixture was stirred for ten minutes at 85 C. Brine (50 mL) was added and the mixture was extracted twice with ether (2 x 150 mL). The combined ether phases were washed twice with saturated aqueous sodium bicarbonate (2 x 150 mL). The ether phase was dried (MGS04) and was concentrated in vacuo to 1.4 g of an orange oil that was purified by flash chromatography. Elution with a gradient (100% hexanes to 1: 3 hexanes/ethyl acetate over 72 minutes) afforded a solid with minor impurities. The solid was dissolved in dichloromethane and vacuum filtered through silica to afford 0.135 g (9.8 % yield over two steps) of a yellow solid ; mp 128-128.5 C ; H-NMR (400 MHz; CDCl3) IB 9.80 (s, 1H), 7.40 (m, 3H), 6.77 (m, 2H), 4.83 (d, 2H, J=3.9 Hz), 3.44 (t, 1 H, J=4.1 Hz) ; 19F- NMR (376 MHz; CDCl3) 6-124. 52 (t, 1F, J=10.1 Hz), -125.27 (dd, 1F, J=10.1, 5.1 Hz), – 144.11 (d, 1F, J=7.7 Hz); MS (APCI+) 407.8 (M+1, 28), 389.8 (100); (APCI-) 405.8 (M-1, 100), 402.8 (53); IR 1662,1529, 1503,1260, 1067 CM~1 ; % C (calculated for C14H9F31NO2/FOUND) 41.30/41. 52, % H 2.23/2. 08, % N 3.44/3. 45.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3,4-Difluoro-2-((2-fluoro-4-iodophenyl)amino)benzoic acid, its application will become more common.

Reference:
Patent; WARNER-LAMBERT COMPANY LLC; WO2005/7616; (2005); A1;,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com