Tag: M.W=200-300

Some common heterocyclic compound, 64695-82-5, name is 2-Bromo-4,5-difluorobenzonitrile, molecular formula is C7H2BrF2N, 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. HPLC of Formula: C7H2BrF2N

A solution of 2-bromo-4,5-difluorobenzonitrile (218 mg, 1.00 mmol), (R)-2-amino- 3-cyclopropylpropanamide (188 mg, 1.14 mmol) and DIEA (0.600 mL, 3.45 mmol) in DMSO (3 mL) was stirred at 120 C for 18 h. Water and EtOAc were added. The organic phase was separated, washed with water, dried over Na2S04, concentrated in vacuo to give (R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-3-cyclopropylpropanamide (326 mg).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 64695-82-5, its application will become more common.

Reference:
Patent; PORTOLA PHARMACEUTICALS, INC.; JIA, Zhaozhong, J.; SONG, Yonghong; XU, Qing; KANE, Brian; BAUER, Shawn, M.; PANDEY, Anjali; WO2012/61418; (2012); A2;,
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Some common heterocyclic compound, 114897-91-5, name is 2-(4-Bromo-2-fluorophenyl)acetonitrile, molecular formula is C8H5BrFN, 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. Safety of 2-(4-Bromo-2-fluorophenyl)acetonitrile

To a solution of Mel (3.2 mL, 49.3 mmol) in anhydrous DMF (82 mL) at 0 C was added NaH (60%, 2.0 g), followed by (4-bromo-2-fluorophenyl) acetonitrile (3.5 g, 16.4 mmol). The mixture was slowly warmed up to room temperature and stirred for 3 hours. The reaction was quenched by the addition of saturated NH4CI and extracted with EtOAc (3 x 150 mL). The combined organic extracts were washed with brine, dried with NA2SO4 and evaporated to dryness. The mixture was purified by flash column chromatography (0-20 % EtOAc in hexanes) to give the product (3. 0 g, 77% yield).’H NMR (300 MHz, CDC13) B : 1.78 (s, 6 H), 7.26-7. 42 (m, 3 H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 114897-91-5, its application will become more common.

Reference:
Patent; PFIZER INC.; WO2004/74270; (2004); A2;,
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Electric Literature of 1953-99-7, 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. 1953-99-7, name is 3,4,5,6-Tetrachlorobenzene-1,2-dicarbonitrile belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

Synthesis Example 1-Chloronaphthalene (500 parts) was added to tetrachlorophthalodinitrile (150 parts). After stirring the resultant mixture in a nitrogen atmosphere at room temperature for 30 minutes, boron trichloride (48 parts) was added. Subsequently, heating was conducted at a ramp rate of 1.6°C/min from room temperature to a temperature at which the formation of a subphthalocyanine began to take place (at that time, the reaction mixture turned into a violet color; the initiation temperature of the formation of the subphthalocyanine is 120°C to 130°C). The reaction mixture was heated further at the same ramp rate to 150°C, and at 150°C, was stirred under heating for 180 minutes. After allowed to cool down, the reaction mixture was introduced into methanol. The precipitate was collected by filtration, washed successively with water, acetone and toluene in this order, and then dried under heat in a vacuum (<1 mmHg, 180°C, 12 hr) to obtain a Cl-dodecachlorosubphthalocyanine boron complex represented by the below-described formula (143 parts, yield: 900). As a result of x-ray diffraction of the thus-obtained compound, strong diffraction peaks appeared around diffraction angles (2psi) of 6. 9°, 7.4°, 20.2°, 20.6°, 26.6° and 30.0° (FIG. 1). Further, its IR absorption spectrum presented at 880 cm-1 a strong absorption ascribable to a B-Cl bond. When measured by a high-performance liquid chromatograph ("MODEL 860-CO", manufactured by JASCO Corporation; column: "YMC-PACK PRO C18", manufactured by YMC Co., Ltd.; mobile phase: THF_water=80:20), the compound in which X was a chlorine atom was found to account for 100percent. The synthetic route of 3,4,5,6-Tetrachlorobenzene-1,2-dicarbonitrile has been constantly updated, and we look forward to future research findings. Reference:
Patent; DAINICHISEIKA COLOR & CHEMICALS MFG. CO. LTD.; Nippon Steel Chemical Co., Ltd.; EP1772494; (2007); A1;,
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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. 144649-99-0, name is 5-Bromo-2-methoxybenzonitrile belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. Safety of 5-Bromo-2-methoxybenzonitrile

Example 35 1,1-Dimethylethyl{[5-bromo-2-(methyloxy)phenyl]methyl}carbamate NaBH4 (2.9 g, 75.5 mmol) was cautiously added in several portions to a solution of NiCl2 (2.6 g, 19.8 mmol), Boc2O (8.2 g, 37.7 mmol) and 5-bromo-2-(methyloxy)benzonitrile (4.0 g, 18.9 mmol) in dry EtOH (70 mL) at 0 C. Once the reaction had subsided, the mixture was left to stir at room temperature for 3 h. Ethanol was removed under reduced pressure and the residue was dissolved in EtOAc and saturated solution of NaHCO3, then filtered and the aqueous layer was repeatedly washed with EtOAc. The combined organic phases were dried Na2SO4. The crude product was purified by flash column chromatography to give the captioned the product (1.5 g yield: 25%). 1H NMR (400 MHz, CDCl3) delta 7.36-7.33 (m, 2H), 6.74 (d, J=8.8 Hz, 1H), 4.97 (br, 1H), 4.27 (d, J=4.8 Hz, 1H), 3.82 (s, 3H), 1.45 (s, 9H); 13C NMR (400 MHz, CDCl3) delta 156.5, 155.8, 131.7, 131.1, 129.3, 111.8, 79.5, 55.5, 39.9, 26.4. HPLC: retention time.

The synthetic route of 144649-99-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Glaxo Group Limited; US2009/203677; (2009); A1;,
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Electric Literature of 213598-11-9, 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 213598-11-9 as follows.

To a solution of methyl 3-cyano-4-hydroxybenzoate (82 g, 463 mmol; J. Med. Chem, 2002,45, 5769) in dimethylfonnamide (800 mL) was added 2-iodopropane (93 mL, 926 mmol) and potassium carbonate (190 g, 1.4 mol). The resulting mixture was heated at 50 C for 16 h, at which time it was allowed to cool to room temperature. The reaction was filtered and the mother liquor diluted with 0.5 N sodium hydroxide (1 L). The resulting mixture was extracted with ether (2 x I L) and the organics washed with 1 N HCI (1 L) and brine (700 mL), dried (MgSO4) and concentrated to give 100 g (-100%) of methyl 3-cyano-4- [(1-methylethyl) oxy]benzoate as a yellow solid. 3-Cyano-4-[(1-methylethyl)oxy]benzoic acid: [00392] To a cooled (0 C) solution of methyl 3-cyano-4-[(1-methylethyl)oxyJbenzoate (100 g, 463 mmol) in tetrahydrofuran (500 mL) was added 10% potassium hydroxide (500 mL). The resulting solution was allowed to warm to room temperature and maintained for 16 h, at which time it was concentrated to remove the tetrahydrofuran. The residue was diluted with water (500 mL) and washed with ether (2 x 500 mL). The aqueous layer was then acidified with 3 N HCI and stood for 2 h. The solids were collected by filtration and washed several times with water, then dissolved in methylene chloride (1 L). The mostly homogeneous mixture was filtered through Celite and concentrated to a minimal volume of methylene chloride. Collection ofthe solids by filtration gave 82 g (87%) of 3-cyano-4-[(1- methylethyl)oxy]benzoic acid as a white solid. Scheme B: Reagents and Conditions: a) 4N HCI/dioxane, rt; b) HBTU, i-Pr2NEt, DMF, rt; c) 1- ethoxyvinyltn-n-butyltin, PdCh(PPh3)2, dioxane, 100 C; d) NBS, THF/HzO (3:1), rt; e) 2- amino-3-picoline, NaHC03, i-PrOH, 80 C . (3tS)-3-Amino-4-(4-bromophenyl)-1 -butane. hydrochloride. [00393] 1,1-Dimethylethyl {(I S)-l-[( 4-bromophenyl)methyl]-3- hydroxypropyl}carbamate (4.4 g, 12.8 mmol) was dissolved in 4N HCl/dioxane (20 mL). After 2 h, the reaction mixture was concentrated in vacuo to give 3.69 g (94%) of the title compound as a white solid. LC/MS (ES) m/e 244.0 (M + H)+. N- {( 1 S)- I -[ (4-Bromophenyl)methyl]-3-hydroxypropyl }-3-cyano-4-[(1- methylethyl)oxy]benzamide. [00394] To a suspension of (3S)-3-Amino-4-(4-bromophenyl)-1-butanol hydrochloride (1.80 g, 6.42 mmol) in dry DMF (32 mL) was added N, N-diisopropylethyl amine (2.49 g, 19.3 mmol) and the resultant clear solution was stirred for 3 min. 3-Cyano-4-[(1- methylethyl) oxy]benzoic acid (1.45 g, 7.06 mmol) and HBTU (2.68 g, 7.06 mmol) were added and the reaction was stirred at rt under nitrogen. After 1.5 h, the reaction mixture was quenched with water (50 mL) and extracted with EtOAc (3 X 30 mL). The extracts were dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (75% EtOAc/hexanes) to give 2.18 g (78%) of the title compound as a white solid. LC/MS (ES) m/e 431.2 (M + H)+. N-«(1S)-I- {[ 4-(Bromoacetyl)phenyl]methyl }-3-hydroxypropyl)-3-cyano-4-[(1- methylethyl) oxy]benzamide. [00395] A flask, dried with a heat gun under argon purge, was charged with N-{(1S)-1- [(4-bromophenyl)methyl]-3-hydrox5propyl}-3-cyano-4-[(1-methylethyl)oxy]benzamide (1.0 g, 2.32 mol). dichlorobis(triphenylphosphine)-palladium(II) (81 mg, 0.116 mol), tributyl(1- ethoxyvinyl) tin (1.68 g, 4.64 mmol), and 1,4-dioxane (15 mL). The mixture was stirred at 100 C for 2 hours under argon. Upon completion, as monitored by LCMS, the reaction was concentrated under reduced pressure and the residue was purified immediately on deactivated silica gel (65% EtOAc/hexanes with 5% triethylamine) to give 720 mg (1.70 mmol) of enol ether intennediate as a colorless foam which was immediately dissolved in THF:H20 (3: 1, 18 mL) and treated with N-bromosuccinimide (3 IS mg, 1.79 mmol). After 15 min at rt, the reaction mixture was concentrated under reduced pressure and the crude residue was diluted with EtOAc (30 mL), washed with biine (10 mL) and water (10 mL) and concentrated under reduced pressure. The residue was purified by silica gel chromatography (80% EtOAc/hexanes) to give 651 mg (59%) of N-«(lS)-I- {[ 4-(bromoacetyJ)phenyl)methyl}-3- hydroxypropyl)-3-cyano-4-[(l -methylethyl)oxy]benzamide as a white tacky solid. LC/MS (ES) m/e 473.2 (M + H)+. 3-Cyano-N ((1S'(at)-3-hydroxy-1-{[(at)4-(8-methylimidazo[1,2-a]p(at)a-idin-2- yl)phenyl ] methj/I ) propyl)-4-[ ( 1 -methyl ethyl)oxy]benzamide. [00396] To a solution of N-( (1 S)-l- {[ 4-(bromoacetyl)phenyl]methyl }-3- hydroxypropyl)-3-cyano-4-[(1-methylethyl)oxy]benzamide (300 mg, 0.634 mmol) in i-PrOH (6 mL) was added 2-amino-3-picoline (Aldrich, 69 mg, 0.634 mmol) followed by solid NaHCO3 (64 mg, 0.761 mmol). The resultant suspension was heated to 80 C. After 7 h, a majority of the i-PrOH was removed under reduced pressure and the residue was dissolved in 3% MeOH/EtOAc (30 mL) and washed with water (10 mL) and brine (10 mL). The combined aqueous layers were extracted with 3% MeO…

According to the analysis of related databases, 213598-11-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; CYTOKINETICS, INC.; SMITHKLINE BEECHAM CORPORATION; WO2005/107762; (2005); A2;,
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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 185836-35-5 as follows. Recommanded Product: 4-(Benzyloxy)-2-fluorobenzonitrile

Step 2: Production of 4-benzyloxy-2-fluoro-N-hydroxybenzamidine To a suspension of 4-benzyloxy-2-fluorobenzonitrile (15.0 g, 66 mmol) in water (150 ml) and ethanol (150 ml) were added hydroxylamine hydrochloride (6.42 g, 92.4 mmol) and sodium carbonate (10.5 g, 99.0 mmol), and the mixture was heated under reflux for 18 hr. The reaction mixture was appropriately evaporated under reduced pressure and the residue was extracted with chloroform. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the obtained solid was washed with a mixed solvent of n-hexane:ethyl acetate=1:1 to give 4-benzyloxy-2-fluoro-N-hydroxybenzamidine (14.7 g, yield 86%). 1H-NMR(400MHz, deltappm, DMSO-d6): 9.51(1H, s), 7.31-7.45 (6H, m), 6.92(1H, dd, J=12.8, 2.0Hz), 6.85(1H, dd, J=8.8, 2.8Hz), 5.71(2H, s), 5.14(2H, s).

According to the analysis of related databases, 185836-35-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Japan Tobacco Inc.; EP1688420; (2006); A1;,
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1897-41-2, name is 2,3,5,6-Tetrachloroterephthalonitrile, belongs to nitriles-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: 2,3,5,6-Tetrachloroterephthalonitrile

Comparative Example 3 Preparation of 2,3,5,6-tetrachloro-1,4-benzenedicarboxylic acid (compound 2) from 2,3,5,6-tetrachloro-1,4-benzenedicarbonitrile (compound 3) 5.32 g (0.02 mol) of 2,3,5,6-tetrachloro-1,4-benzenedicarbonitrile and 17.65 g of 90.0percent sulfuric acid were charged into a reactor, and a hydrolysis of 2,3,5,6-tetrachloro-1,4-benzenedicarbonitrile was performed under atmospheric pressure. The temperature and reaction time were as specified in Table 1. After the completion of the reaction, the same processing as in Example 1 was conducted. As a result, 2,3,5,6-tetrachloro-1,4-benzenedicarboxylic acid was obtained. Yield: 5.9 g (isolation yield 97percent), and IR (KBr):

The synthetic route of 1897-41-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SDS Biotech K.K.; US2001/25121; (2001); A1;,
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179897-89-3, name is 5-Bromo-2-fluorobenzonitrile, belongs to nitriles-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. HPLC of Formula: C7H3BrFN

6(pinacolato)diboron (1.9 g, 7.48 mmol), and KOAc (1.47 g, 14.98 mmol) in 1,4- dioxane (10.0 mL) that was degassed with argon for 10 min was added PdCl2(dppf) (10 mg, 0.014 mmol). The reaction mixture was heated to 100 0C overnight. The reaction mixture was filtered through Celite 521 and rinsed through with EtOAc (10 mL). The filtrate was concentrated in vacuo and treated with CH2Cl2 (10 mL) and water (10 mL). The layers were separated, and the aqueous layer was extracted with CH2Cl2 (5 mL). The combined organic layers were washed with brine (5 mL), dried over Na2SO4, filtered, and concentrated in vacuo onto Isolute. Purification via flash column chromatography (0- 20% EtOAc/hexanes) afforded the title compound (1.03 g, 72%). LC-MS m/z 248 (M+H)+, 1.15 min (ret time).

The synthetic route of 179897-89-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GLAXO GROUP LIMITED; BULLION, Ann, Marie; BUSCH-PETERSEN, Jakob; EVANS, Brian; NEIPP, Christopher, E.; MCCLELAND, Brent, W.; NEVINS, Neysa; WALL, Michael, D.; WO2011/25799; (2011); A1;,
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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. 916792-13-7, name is 4-Bromo-2-fluoro-5-methylbenzonitrile, A new synthetic method of this compound is introduced below., Formula: C8H5BrFN

A mixture of 4-bromo-2-fluoro-5- methylbenzonitrile (4.0 g, 18.7 mmol), potassium vinyltrifluoroborate (2.8 g, 20.6 mmol) and Pd(dppf)2Cl2 (0.4 g, 0.6 mmol) in 40 mL of EtOH and 13 mL of TEA was refluxed under Ar for 4 hours. The reaction mixture was concentrated, and the residue was purified by column chromatography (petrol ether : EtOAc = 10 : 1) to afford the title compound as a yellow solid

The synthetic route of 916792-13-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK SHARP & DOHME CORP.; PASTERNAK, Alexander; PIO, Barbara; CHOBANIAN, Harry, R.; SHI, Zhi-Cai; DONG, Shuzhi; GUO, Yan; WALSH, Shawn, P.; GUO, Zhiqiang; FERGUSON, Ronald, D.; CATO, Brian; (114 pag.)WO2016/60941; (2016); A1;,
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Electric Literature of 1953-99-7, 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. 1953-99-7, name is 3,4,5,6-Tetrachlorobenzene-1,2-dicarbonitrile belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

A reaction was performed and the reaction product was treated by following the procedure of Example 1 while omitting the addition of sodium hydroxide. When the benzonitrile solution as the mother liquor was similarly analyzed, it was found to contain 0.200 g of benzoic acid fluoride (3600 ppm based on the amount of 3,4,5,6-tetrafluorophthalonitrile). The stainless steel reaction vessel showed a sign of slight corrosion.

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, 3,4,5,6-Tetrachlorobenzene-1,2-dicarbonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Nippon Shokubai Co., Ltd.; US6392084; (2002); B1;,
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