Month: May 2021

Synthetic Route of 2106-04-9,Some common heterocyclic compound, 2106-04-9, name is 3-Chloro-2-fluoroaniline, molecular formula is C6H5ClFN, 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-chloro-2-fluoroaniline (0.239 mL, 2.17 mmol) was added to a stirred suspension of methyl 8-(l-bromoethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate (215 mg, 0.54 mmol) dissolved in DCM (3 mL) at room temperature. The resulting suspension was stirred for 16 hrs then the temperature was increased to 50C for 16 hrs. The crude product was purified by flash chromatography on silica gel eluting with 5% methanol in DCM. The solvent was evaporated to dryness to afford methyl 8-(l-(3-chloro-2- fluorophenylamino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate (206 mg, 82 %) as a white solid. Mass Spectrum: M+H+ 461.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3-Chloro-2-fluoroaniline, its application will become more common.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; BARLAAM, Bernard, Christophe; DEGORCE, Sebastien, Louis; LAMBERT-VAN DER BREMPT, Christine, Marie, Paul; MORGENTIN, Remy, Robert; PLE, Patrick; WO2011/51704; (2011); A1;,
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Some common heterocyclic compound, 2106-04-9, name is 3-Chloro-2-fluoroaniline, molecular formula is C6H5ClFN, 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. Quality Control of 3-Chloro-2-fluoroaniline

A round bottom flask was charged with 1 eq of 3-chloro-2-fluoroaniline (3A), l-methyl-2-pyrrolidinone (about 1.5 M 3A in NMP), 2.2 eq of sodium cyanide, and 1.35 eq of nickel() bromide at RT under N2. The concentration was halved by die introduction of additional NMP under N2 and the solution was gently warmed to 200+/- 5C and stirred for 4 days under N2. The reaction mixture was allowed to cool to room temperature. The reaction mixture was diluted with 30 volumes of teft-hutyl methyl ether (MTBE) and filtered through celite. The celite pad was then rinsed with 10 volumes of MTBE. The organics were washed with 40 volumes of brine, 2 x 40 volumes of water and 40 volumes of brine. The combined organics were dried over sodium sulfate and concentrated to afford a brown solid, which was dried under vacuum (~30 in Hg) at 400C for 8 hours to afford the compound of Formula 3B (71% yield).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2106-04-9, its application will become more common.

Reference:
Patent; CYTOKINETICS, INC.; WO2007/70683; (2007); A2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Synthetic Route of 174913-12-3,Some common heterocyclic compound, 174913-12-3, name is 1-Bromo-3-chloro-5-methoxybenzene, molecular formula is C7H6BrClO, 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.

[00233] Step a: A solution of l-bromo-3-chloro-5-methoxybenzene (835 mg, 3.77 mmol), and l,3,5-trichloro-l,3,5-triazinane-2,4,6-trione (299 mg, 1.29 mmol) in DMF (18 mL) was stirred 16 h under N2 and 50 C. After cooling to RT, the reaction mixture was diluted with aqueous NH4C1 and extracted with Et20. The combined organic phases were dried over MgS04, filtered, concentrated, and the resulting residue was purified by silica chromatography (0 to 25% gradient of EtO Ac/heptane) to l-bromo-2,3-dichloro-5-methoxybenzene (720 mg, 2.81 mmol). NMR (400 MHz, CHLOROFORM-^ delta ppm 7.14 (d, J=2.76 Hz, 1 H), 7.01 (d, J=3.01 Hz, 1 H), 3.81 (s, 3 H).

The synthetic route of 174913-12-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NOVARTIS AG; CHEN, Christine Hiu-tung; CHEN, Zhuoliang; FORTANET, Jorge Garcia; GRUNENFELDER, Denise; KARKI, Rajesh; KATO, Mitsunori; LAMARCHE, Matthew J.; PEREZ, Lawrence Blas; STAMS, Travis Matthew; WILLIAMS, Sarah; WO2015/107493; (2015); A1;,
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Synthetic Route of 445-14-7, 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 445-14-7 as follows.

40% HBr (2.20 mL, 15.34 mmol) was dissolved in H2O (2 mL), then at 0 C,2-Amino-4-chlorobenzotrifluoride (0.50 g, 2.56 mmol) was added to the reaction mixture, followed by 0 C,An aqueous solution of sodium nitrite (sodium nitrite (0.21 g, 3.07 mmol) dissolved in 2 mL of water) was added dropwise to the reaction mixture.After the reaction solution was stirred at 0 C for half an hour, additional cuprous bromide (0.63 g, 4.35 mmol) of 40% HBr (2.20 mL, 15.34 mmol) andA mixed solution of H2O (3 mL).The reaction solution was stirred at 75 C for 3 hours, and then cooled to room temperature.It was then extracted with ethyl acetate (40 mL x 4).The combined organic phases were washed with brine (80 mL x 2).Dry with anhydrous Na2SO4,The title compound was obtained as a yellow liquid after concentration under reduced pressure.(0.76g, 100%).

According to the analysis of related databases, 445-14-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Guangdong Dongyangguang Pharmaceutical Co., Ltd.; Jiatuo Sciences Corporation; Xi Ning; Li Xiaobo; Zhou Shiqing; (62 pag.)CN103833753; (2017); B;,
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Reference of 33863-76-2,Some common heterocyclic compound, 33863-76-2, name is 1-Bromo-3-chloro-5-fluorobenzene, molecular formula is C6H3BrClF, 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.

steps 1 and 2-A solution of 1-bromo-3-chloro-5-fluoro-benzene (42a, 55 g, 263 mmol) was cooled to 0 C. and treated with a 25% methanolic sodium methoxide solution (68 mL, 315 mmol) and heated to 40 C. for 3 h. The solution was cooled and partitioned between water (1 L) and a 1:1 mixture of hexane/diethyl ether (3×200 mL). The combined extracts were washed with brine (60 mL), dried (Na2SO4), filtered and the solvents evaporated in vacuo to afford 42b as an oil (57.3 g, 92% pure, 238 mmol). The ether 42b (43 g, 173 mmol) was treated with glacial HOAc (150 mL) and 48% aqueous HBr (100 mL) and heated to 120 C. After 40 h, the volatiles were removed while heated to 80 C. and then cooled to RT. The residue was partitioned between water (100 mL) and DCM (3×250 mL). The combined extracts were washed with H2O (50 mL), aqueous NaHCO3 solution (2×50 mL), brine (50 mL), and (MgSO4). The solvents were removed to afford 23.3 g of 42c as a grey solid.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1-Bromo-3-chloro-5-fluorobenzene, its application will become more common.

Reference:
Patent; Roche Palo Alto LLC; US2006/25462; (2006); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

39226-96-5, name is (2-Chloro-3-(trifluoromethyl)phenyl)methanamine, belongs to chlorides-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. Recommanded Product: 39226-96-5

Example 51 N-{[2-chloro-3-(trifluoromethyl)phenyl]methyl}-1-methyl-5-oxoprolinamide 1-methyl-5-oxoproline (2.27 g, 15.88 mmol, prepared as described below) was dissolved in dichloromethane (150 ml) and to this was added N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride (3.35 g, 17.47 mmol), and 1-hydroxybenzotriazole (2.36 g, 17.47 mmol). The mixture was stirred for ~10 minutes and then triethylamine (2.21 ml, 15.88 mmol) and {[2-chloro-3-(trifluoromethyl)phenyl]methyl}amine (3.66 ml, 17.47 mmol) were added and the mixture was left stirring at room temperature overnight (~17 hrs). A white precipitate formed during this time. The mixture was then treated with saturated aqueous sodium hydrogen carbonate (~100 ml) and stirred for 10 minutes. The organic layer was separated using a hydrophobic frit and then 2N aqueous hydrogen chloride was added and mixed and separated again. The organic layer was concentrated to give white solids (~2.5 g). The solid was dissolved in ethyl acetate (~200 ml) and washed with water (4*50 ml) followed by brine (50 ml). The organic layer was then dried by passing through a phase separator and concentrated to give pure N-{[2-chloro-3-(trifluoromethyl)phenyl]methyl}-1-methyl-5-oxo-L-prolinamide as a fine white solid (2.48 g). LC/MS [M+H]+=335, retention time=2.24 minutes. 1H NMR (CDCl3, 500 MHz) delta 2.02 (m, 1H), 2.35 (m, 1H), 2.39 (m, 1H), 2.47 (m, 1H), 2.81 (s, 3H), 4.00 (dd, 1H, J=8.9, 4.2 Hz), 4.60 (dd, 1H, J=15.1, 6.2 Hz), 4.65 (dd, 1H, J=15.1, 6.2 Hz), 6.56 (broad t, 1H, J=5.8 Hz), 7.38 (t, 1H, J=7.7 Hz), 7.60 (dd, 1H, J=7.6, 1.0 Hz), 7.68 (dd, 1H, J=7.9, 1.2 Hz); 13C NMR delta 176.0, 171.5, 137.5, 133.9, 131.7, 129.3, 127.4, 127.0, 122.8, 63.8, 41.8, 29.4, 29.2, 23.4.

The synthetic route of 39226-96-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GLAXO GROUP LIMITED; US2008/9541; (2008); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Related Products of 39226-96-5, A common heterocyclic compound, 39226-96-5, name is (2-Chloro-3-(trifluoromethyl)phenyl)methanamine, molecular formula is C8H7ClF3N, 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.

Example 100 N-{[2-chloro-3-(trifluoromethyl)phenyl]methyl}-1-(2,2-dimethylpropyl)-5-oxoprolinamide (E100) 1-(2,2-dimethylpropyl)-5-oxoproline (0.100 g, 0.5 mmol, prepared as described below) was dissolved in dichloromethane (5 ml) and to this was added N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride (0.191 g, 1 mmol), and 1-hydroxybenzotriazole (0.135 g, 1 mmol). The mixture was stirred for 30 minutes at room temperature and then {[2-chloro-3-(trifluoromethyl)phenyl]methyl}amine (0.209 g, 1 mmol) was added and the mixture was stirred overnight at room temperature. The mixture was then washed sequentially with water, 3N aqueous citric acid, and three more times with water then dried by filtering through a hydromatrix cartridge (Varian 5 g). The solvent was then evaporated and the residue was purified by mass-directed automated HPLC to give pure N-{[2-chloro-3-(trifluoromethyl)phenyl]methyl}-1-(2,2-dimethylpropyl)-5-oxoprolinamide. LC/MS [M+H]+=391/393, retention time=2.78 minutes. N-{[2-chloro-3-(trifluoromethyl)phenyl]methyl}-1-(2,2-dimethylpropyl)-5-oxoprolinamide was prepared in an analogous manner to that described for example 100 but using 1-(2,2-dimethylpropyl)-5-oxoproline prepared as described below. LC/MS [M+H]+=391/393, retention time=2.76 minutes.

The synthetic route of 39226-96-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GLAXO GROUP LIMITED; US2008/9541; (2008); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Electric Literature of 883499-24-9, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 883499-24-9, name is 1-Bromo-2-chloro-3-fluorobenzene belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

To a mechanical-stirred solution of diisopropylamine (5.02 g, 7.08 ml, 49.7 mmol, Eq:1.04) in THF (35 ml) was added dropwise (5 mm) at -20C n-butyllithium, 1.6 M in hexane (31ml, 49.7 mmol, Eq: 1.04) and stirred at 0 C for 20 minutes. The mixture was cooled to -78 Cfollowed by dropwise addition (20 minutes) of a solution of 1-bromo-2-chloro-3-fluorobenzene(10 g, 47.7 mmol, Eq: 1) in THF (10 ml) and the thick yellow suspension was stirred at -78 Cfor 60 mm. Then was added dropwise (5 minutes – exotherm) N,N-dimethylformamide (5.23 g,5.55 ml, 71.6 mmol, Eq: 1.5), the cooling bath was removed and the mixture was allowed to warm to -20 C to give complete conversion. At -20 C the clear yellow solution was quenched with sat NH4C1 (100 ml) and extracted with TBME (100 ml). The aqueous layer was extracted again with TBME (50 ml). The organic layers were dried and evaporated at only 50 mbar forshort time. The yellow residue was dissolved in heptane/ethyl acetate 10:1 (ca. 30 ml) at 55 C,concentrated to 1/3 and stirred to 22 C while crystallisation started. After 30 minutes thesuspension was cooled to 0 C for 30 minutes, the solid was filtered off, washed with heptane (2x 15 ml) and dried (only short time) to give 4-bromo-3-chloro-2-fluorobenzaldehyde (5.27 g,47%) as light yellow solid. The filtrate was evaporated and purified by flash chromatography (silica gel, 70 g, adsorbed on isolute sorbent HM-N, EtOAc in heptane, 0% to 5% ) to give additional compound (4.073 g, 36%) as off-white solid.GC-MS: mlz = 235.9 M.+ (monoisotopic mass 235.90)

The synthetic route of 1-Bromo-2-chloro-3-fluorobenzene has been constantly updated, and we look forward to future research findings.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; ALANINE, Alexander; BEIGNET, Julien; BLEICHER, Konrad; FASCHING, Bernhard; HILPERT, Hans; HU, Taishan; MACDONALD, Dwight; JACKSON, Stephen; KOLCZEWSKI, Sabine; KROLL, Carsten; SCHAEUBLIN, Adrian; SHEN, Hong; STOLL, Theodor; THOMAS, Helmut; WAHHAB, Amal; ZAMPALONI, Claudia; (623 pag.)WO2017/72062; (2017); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 60811-21-4, name is 4-Bromo-2-chloro-1-fluorobenzene belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. Computed Properties of C6H3BrClF

(2) The corresponding arylmagnesium bromide was prepared from 406 g (1.94 mol) of 4-bromo-2-chlorofluorobenzene and 48.6 g (2.00 mol) of magnesium turnings in 1,300 ml of anhydrous tetrahydrofuran by the customary process. The solution thus obtained was added dropwise to a solution of 278.3 g (2.3 mol) of allyl bromide in 200 ml of anhydrous tetrahydrofuran at 30-45 C. The mixture was then heated under reflux for 0.5 h, allowed to stand at room temperature for 16 h and poured onto 1.5 liters of ice-water. After acidification using a little 2N hydrochloric acid, the mixture was extracted twice using 1 liter of hexane each time. The extracts were washed three times with water, dried over Na2 SO4 and evaporated. The residue yielded 235 g (71%) of 3-(3-chloro-4-fluorophenyl)propene of b.p.10 =72 C. with a purity of 98.7% (determined by gas chromatography) on subsequent distillation.

The synthetic route of 60811-21-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Hoechst Aktiengesellschaft; US4920212; (1990); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 4584-46-7, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 4584-46-7, name is 2-Chloro-N,N-dimethylethanamine hydrochloride belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

A mixture of 2-(2,4-dimethoxy-benzyl)-4-hydroxy-isoindole-1,3-dione (317 mg, 1.01 mmol), 2-dimethylaminoethyl chloride hydrochloride (160 mg, 1.11 mmol) and potassium carbonate (350 mg, 2.5 mmol) in DMF (4 mL) was heated at 60 C. for 18 hours. The mixture was concentrated in vacuo, taken up in ethyl acetate and extracted twice with 1N hydrochloric acid. The aqueous extracts were made basic with solid potassium carbonate and extracted with ethyl acetate (×2). The combined organic extracts were washed with brine, dried (MgSO4) and concentrated to give the title compound (236 mg, 61%) as an off-white solid. 1H NMR (methanol-d4) 7.73 (1H, t), 7.44-7.40 (2H, m), 7.02 (1H, d), 6.51 (1H, d), 6.42 (1H, dd), 4.72 (2H, s), 4.33 (2H, t), 3.80 (3H, s), 3.76 (3H, s), 2.87 (2H, t), 2.40 (6H, s). MS: [M+H]+ 385.

The synthetic route of 2-Chloro-N,N-dimethylethanamine hydrochloride has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTEX THERAPEUTICS LIMITED; US2010/152184; (2010); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics