Category: 875664-41-8

Electric Literature of 875664-41-8, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 875664-41-8 name is 3-Bromo-4,5-difluoroaniline, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

1 -methyl-4-[(3 -methyloxetan-3 -yl)sulfamoyl]pyrrole-2-carboxylic acid (200 mg, 0.73 mmol) was dissolved in N,N-dimethylformamide (2 mL). HATU (0.35 g, 0.91 mmol) was added followed by diisopropylethylamine (0.38 mL, 2.19 mmol). The resulting mixture was stirred for 30 minutes at room temperature. Then, 4-fluoro-3,5-dimethylaniline (0.2 g, 1.46 mmol) was added. The resulting mixture was stirred for 24 hours and next poured onto 10 mL of ice. The mixture was extracted using 2-Me-THF (3 x 10 mL). The combined organics were washed withbrine, dried on Na2SO4, filtered and concentrated in vacuo. The obtained residue was purified by silica gel column chromatography using gradient elution from heptane to EtOAc. (100:0 to 0:100). The desired fractions were concentrated in vacuo and dried in a vacuum oven at 55C for24 hours yielding compound 80 (130 mg):Compound 100 to 105 were prepared similarly as described for compound 80, using 1-methyl-4-[[(1 S)-2,2,2-trifluoro- 1 -methyl-ethyl]sulfamoyl]pyrrole-2-carboxylic acid instead of 1 -methyl-4-[(3 -methyloxetan-3 -yl)sulfamoyl]pyrrole-2-carboxylic acid and the corresponding aniline instead of 4-fluoro-3 ,5 -dimethylaniline. After addition of the aniline, the mixture was stirred at 50C forhours instead of 24 hours at room temperature.Crude compound 100 was purified by silica gel chromatography heptane-EtOAc 100/0 to 0/100. The product was crystallized from diisopropylether (15 mL)/iPrOH (3.5 mL). The product wasfiltered off, washed with diisopropylether (3x), and dried at 50C in vacuo, resulting in compound 100 (251 mg). MethodA; Rt: 1.98 mi mlz: 489.8 (M-H) Exactmass: 491.0. ?HNMR (400 MHz, DMSO-d6) oe ppm 1.08 (d, J=6.8 Hz, 3 H), 3.84 – 4.00 (m, 4 H), 7.36 (d, J=2.0Hz, 1 H), 7.66 (d, J=1.8 Hz, 1 H), 7.80 – 7.93 (m, 2 H), 8.20 (br. s., 1 H), 10.31 (br. s., 1 H).?9FNMR (377 MHz, DMSO-d6) oe ppm -138.51 –138.34 (m, 1 F), -133.99 –133.81 (m, 1 F), -76.07 (d, J=7.9 Hz, 3 F). Differential scanning calorimetry: From 30 to 300 C at 10C/mm:peak at 199.0 C.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3-Bromo-4,5-difluoroaniline, and friends who are interested can also refer to it.

Reference:
Patent; JANSSEN R&D IRELAND; VANDYCK, Koen; HACHE, Geerwin, Yvonne, Paul; LAST, Stefaan, Julien; MC GOWAN, David, Craig; ROMBOUTS, Geert; VERSCHUEREN, Wim, Gaston; RABOISSON, Pierre, Jean-Marie, Bernard; WO2014/184350; (2014); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

875664-41-8, name is 3-Bromo-4,5-difluoroaniline, belongs to bromides-buliding-blocks compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. name: 3-Bromo-4,5-difluoroaniline

N-Boc-(35)-l-pyrrolidine-3-carboxylic acid [CAS 140148-70-5] (1 g, 4.65 mmol), 3-bromo-4,5-difluoroaniline (0.96 g, 4.65 mmol) and HATU (2.12 g, 5.58 mmol) were added to CH2CI2 (10 mL). N,N-diisopropylethylamine (2.4 mL, 13.9 mmol) was added and the resultant mixture stirred at room temperature for 4 hours. The mixture was partitioned with HCl (1M, aq., 20 mL). The organic layer was separated and the solvent removed under reduced pressure. The crude was purified via silica gel column chromatography using a heptane to ethyl acetate gradient to afford an oil. Subsequent Boc deprotection HCl (6 M in isopropanol, 15h at room temperature) afforded (5)-N-(3-bromo- 4,5-difluorophenyl)pyrrolidine-3-carboxamide hydrochloride that was used as such in the next step without further purification.

The synthetic route of 875664-41-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; JANSSEN R&D IRELAND; VANDYCK, Koen; HACHE, Geerwin Yvonne Paul; KESTELEYN, Bart Rudolf Romanie; RABOISSON, Pierre Jean-Marie Bernard; WO2015/59212; (2015); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Reference of 875664-41-8, These common heterocyclic compound, 875664-41-8, name is 3-Bromo-4,5-difluoroaniline, 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.

3-bromo-4,5-difluoroaniline (2.6 g, 12.8 mmol) in toluene (20 mL) was added dropwise to a solution of 4-chlorosulfonyl-1-methyl-pyrrole-2-carbonylchloride (3100 mg, 12.8 mmol) in toluene (160 mL) at reflux. The reaction mixture was refluxed 2 hours and next allowed to cool to room temperature.

The synthetic route of 875664-41-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; JANSSEN R&D IRELAND; VANDYCK, Koen; HACHE, Geerwin, Yvonne, Paul; LAST, Stefaan, Julien; MC GOWAN, David, Craig; ROMBOUTS, Geert; VERSCHUEREN, Wim, Gaston; RABOISSON, Pierre, Jean-Marie, Bernard; WO2014/184350; (2014); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

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. 875664-41-8, name is 3-Bromo-4,5-difluoroaniline, A new synthetic method of this compound is introduced below., Computed Properties of C6H4BrF2N

To a solution of 4-amino-A/-hydroxy-1 ,2,5-oxadiazole-3-carbimidoyl chloride (Int 7a) (250 mg, 1 .54 mmol) and 3-bromo-4,5-difluoroaniline (320 mg, 1 .54 mmol) in H20 and THF (12 mL, 1 :1 ) was added NaHC03 (194 mg, 2.31 mmol). The mixture was stirred at 65 C for 2 hours. Then the mixture was diluted with EtOAc (50 mL). The organic layer was washed with water (30 mL) and brine (30 mL), dried over Na2S04 and concentrated. The residue was purified by column chromatography on silica gel (PE: EtOAc = 5:1 ) to give the title compound as a white solid.

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; PHENEX DISCOVERY VERWALTUNGS-GMBH; STEENECK, Christoph; KINZEL, Olaf; ANDERHUB, Simon; HORNBERGER, Martin; KLEYMANN, Gerald; HOFFMANN, Thomas; (191 pag.)WO2018/83241; (2018); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

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. 875664-41-8, name is 3-Bromo-4,5-difluoroaniline, A new synthetic method of this compound is introduced below., name: 3-Bromo-4,5-difluoroaniline

This acid (700 mg,2.33mmol), 3-aminobenzonitrile (347.8mg, 2.91 mmol), HATU (1108mg, 2.9l4mmol) andDIPEA (1 .2mL, 6.99 mmol) was dissolved in DMF (7 mL) and the mixture was stirred at roomtemperature for 16 h. The mixture was poured in 100 mL ice water and was extracted withEtOAc. The organic layer was separated, washed with brine, dried (MgSO4), filtered andconcentrated in vacuo. The residue was purified on a silica using a gradient eluent HeptaneEtOAc 100-0 -> 50-50. The product fractions were collected and concentrated in vacuo. The product was crystallized from 2-propanol, filtered off and dried in vacuo, yielding compound 158 (518 mg) as a white solid.Compound 205 (893 mg) was prepared similarly as described for compound 158 using 3-bromo-4,5-difluoroaniline (970 mg, 4.663 mmol) instead of 3-aminobenzonitrile and stirring at 60C during 18 h. The obtained residue was warmed with CH2C12/heptanes and the white solid collected by filtration. Method A: Rt: 1.79 mm mlz: 489.9 (M-H)- Exact mass: 488.98. ?H NMR (400 MHz, DMSO-d6) oe ppm 1.08 (d, J=7.0 Hz, 3 H), 3.84 – 3.99 (m, 1 H), 3.92 (s, 3 H), 7.36 (d,J=1.8 Hz, 1 H), 7.67 (d, J=1.5 Hz, 1 H), 7.80 – 7.93 (m, 2 H), 8.19 (br. s., 1 H), 10.30 (s, 1 H). Differential scanning calorimetry: From 30 to 300 C at 10C/mm: peak at 196.72 C.

The synthetic route of 875664-41-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; JANSSEN R&D IRELAND; VANDYCK, Koen; HACHE, Geerwin, Yvonne, Paul; LAST, Stefaan, Julien; MC GOWAN, David, Craig; ROMBOUTS, Geert; VERSCHUEREN, Wim, Gaston; RABOISSON, Pierre, Jean-Marie, Bernard; WO2014/184350; (2014); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Related Products of 875664-41-8, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 875664-41-8 name is 3-Bromo-4,5-difluoroaniline, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

1 -methyl-4-[(3 -methyloxetan-3 -yl)sulfamoyl]pyrrole-2-carboxylic acid (200 mg, 0.73 mmol) was dissolved in N,N-dimethylformamide (2 mL). HATU (0.35 g, 0.91 mmol) was added followed by diisopropylethylamine (0.38 mL, 2.19 mmol). The resulting mixture was stirred for 30 minutes at room temperature. Then, 4-fluoro-3,5-dimethylaniline (0.2 g, 1.46 mmol) was added. The resulting mixture was stirred for 24 hours and next poured onto 10 mL of ice. The mixture was extracted using 2-Me-THF (3 x 10 mL). The combined organics were washed withbrine, dried on Na2SO4, filtered and concentrated in vacuo. The obtained residue was purified by silica gel column chromatography using gradient elution from heptane to EtOAc. (100:0 to 0:100). The desired fractions were concentrated in vacuo and dried in a vacuum oven at 55C for24 hours yielding compound 80 (130 mg):Compound 100 to 105 were prepared similarly as described for compound 80, using 1-methyl-4-[[(1 S)-2,2,2-trifluoro- 1 -methyl-ethyl]sulfamoyl]pyrrole-2-carboxylic acid instead of 1 -methyl-4-[(3 -methyloxetan-3 -yl)sulfamoyl]pyrrole-2-carboxylic acid and the corresponding aniline instead of 4-fluoro-3 ,5 -dimethylaniline. After addition of the aniline, the mixture was stirred at 50C forhours instead of 24 hours at room temperature.Crude compound 100 was purified by silica gel chromatography heptane-EtOAc 100/0 to 0/100. The product was crystallized from diisopropylether (15 mL)/iPrOH (3.5 mL). The product wasfiltered off, washed with diisopropylether (3x), and dried at 50C in vacuo, resulting in compound 100 (251 mg). MethodA; Rt: 1.98 mi mlz: 489.8 (M-H) Exactmass: 491.0. ?HNMR (400 MHz, DMSO-d6) oe ppm 1.08 (d, J=6.8 Hz, 3 H), 3.84 – 4.00 (m, 4 H), 7.36 (d, J=2.0Hz, 1 H), 7.66 (d, J=1.8 Hz, 1 H), 7.80 – 7.93 (m, 2 H), 8.20 (br. s., 1 H), 10.31 (br. s., 1 H).?9FNMR (377 MHz, DMSO-d6) oe ppm -138.51 –138.34 (m, 1 F), -133.99 –133.81 (m, 1 F), -76.07 (d, J=7.9 Hz, 3 F). Differential scanning calorimetry: From 30 to 300 C at 10C/mm:peak at 199.0 C.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3-Bromo-4,5-difluoroaniline, and friends who are interested can also refer to it.

Reference:
Patent; JANSSEN R&D IRELAND; VANDYCK, Koen; HACHE, Geerwin, Yvonne, Paul; LAST, Stefaan, Julien; MC GOWAN, David, Craig; ROMBOUTS, Geert; VERSCHUEREN, Wim, Gaston; RABOISSON, Pierre, Jean-Marie, Bernard; WO2014/184350; (2014); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 875664-41-8 as follows. Quality Control of 3-Bromo-4,5-difluoroaniline

Compound 99 A mixture of 3-(N-isopropylsulfamoyl)benzoic acid (2.3 g, 9.615 mmol), 3-bromo-4,5- difluoroaniline (2 g, 9.615 mmol) and DIPEA (5 mL) in CH2CI2 (30 mL) was cooled to 0C and HATU (4.39 g, 1 1.538 mmol) was added. The mixture was stirred for 2 hours at 20C. The mixture was washed with IN HC1 (30 mL) and brine (30 mL) and dried over Na2S04. The solvent was removed in vacuo. The residue was purified by silica gel column chromatography (gradient eluent: petroleum ether/ethyl acetate from 100/0 to 70/30) resulting in crude N-(3-bromo-4,5-difluorophenyl)-3-(N-isopropylsulfamoyl)- benzamide (4 g). A mixture of N-(3-bromo-4,5-difluorophenyl)-3-(N-isopropyl- sulfamoyl)benzamide (1 g, 2.308 mmol), methylboronic acid (1 g, 4.616 mmol), CS2CO3 (2.26 g, 6.924 mmol), 2-Dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (95 mg, 0.231 mmol) and Tris(dibenzylideneacetone)dipalladium(0) (0.21 g, 0.231 mmol) in dioxane (15 mL) was heated by microwave irradiation for 40 minutes at 120C under N2 atmosphere. After cooling, the mixture was filtered through celite and the filtrate was evaporated to dryness. The obtained residue was purified by silca gel column chromatography (gradient eluent: petroleum ether/ethyl acetate from 100/0 to 70/30) and further purified by preparative high performance liquid chromatography over reversed phase C-18 (eluent: CH3CN in H20 (0.1% TFA) from 38% to 68%, v/v). The pure fractions were collected and half of the volatiles were removed in vacuo. The mixture was adjusted to pH=7 with Amberlite IRA-900 (OH) anionic exchange resin and the resin was filtered off. The organic solvent was concentrated in vacuo and the aqueous layer was lyophilized to dryness. The obtained product was further purified by silica gel chromatography (gradient eluent: petroleum ether/ethyl acetate from 100/0 to 70/30) resulting in compound 99 (190 mg). Method A; Rt: 6.09 min. m/z : 369.2 (M+H)+ Exact mass: 368.1, 1H NMR (400 MHz, CHLOROFORM- ) delta ppm 8.35 (1 H, t, J=1.5 Hz), 8.09 – 8.17 (2 H, m), 8.04 (1 H, dt, J=8.0, 1.5 Hz), 7.66 (1 H, t, J=8.0 Hz), 7.54 (1 H, ddd, J=11.5, 6.5, 3.0 Hz), 7.14 – 7.22 (1 H, m), 4.72 (1 H, d, J=8.0 Hz), 3.43-3.60 (1 H, m), 2.32 (3 H, d, J=2.0 Hz), 1.10 (6 H, d, J=6.5 Hz).

According to the analysis of related databases, 875664-41-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; JANSSEN R&D IRELAND; LAST, Stefaan Julien; RABOISSON, Pierre Jean-Marie Bernard; ROMBOUTS, Geert; VANDYCK, Koen; VERSCHUEREN, Wim Gaston; WO2014/33170; (2014); A1;,
Bromide – Wikipedia,
bromide – Wiktionary