Category: nitriles-buliding-blocks

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. 66389-80-8, name is tert-Butyl 4-cyanobenzylcarbamate, A new synthetic method of this compound is introduced below., HPLC of Formula: C13H16N2O2

General procedure: To a round-bottom flask equipped with a stir bar was added 28a-b (1.0 eq), hydroxylamine hydrochloride (2.0 eq), NaHCO3 (4.0 eq), and methanol (10 mL/mmol). The reaction was refluxed and stirred in a pre-heated 75 C. oil-bath for 6 h. After cooling to room temperature, the precipitate was filtered off and washed with methanol. The filtrate was concentrated in vacuo and further purified on a silica gel column. Example 89 Synthesis of 215 tert-Butyl (E)-(4-(N?-hydroxycarbamimidoyl)benzyl) carbamate (29a) (0246) The synthesis follows the general procedure described in Example 88. Yield: 65%. MP: 142-145 C. 1H NMR (400 MHz, DMSO-d6) delta 9.57 (s, 1H, -OH), 7.61 (d, J=8.1 Hz, 2H, -ArH), 7.40 (t, J=6.1 Hz, 1H, -NHCO-), 7.22 (d, J=8.1 Hz, 2H, -ArH), 5.77 (s, 2H, -NH2), 4.13 (d, J=6.1 Hz, 2H, -ArCH2-), 1.40 (s, 9H, -CH3).

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; Washington University; Tu, Zhude; Rosenberg, Adam; Liu, Hui; Han, Junbin; US2019/2450; (2019); A1;,
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Adding a certain compound to certain chemical reactions, such as: 36282-26-5, name is 2-Bromo-4-fluorobenzonitrile, belongs to nitriles-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 36282-26-5, category: nitriles-buliding-blocks

To a stirred solution of 2-bromo-4-fluorobenzonitrile (5 g, 25.00 mmol), bis(pinacolato)diboron (9.52 g, 37.5 mmol), potassium acetate (7.36 g, 75.0 mmol), in dioxane (50 mL) argon was purged for 5 mins. PdCl2(dppf)-CH2Cl2 adduct (12.25 g, 15.00 mmol) was added and argon was bubbled through the reaction mixture and heated at 94 C (silicon oil bath) for 14 h. The reaction mixture was cooled to RT, filtered through celite pad, washed with ethyl acetate (200 mL). The organic layer was washed with water (100 mL) and the aq. layer was separated and re-extracted with ethyl acetate (2 x 100 mL). Combined organic extracts were washed with brine, dried over sodium sulfate and solvent was removed under reduced pressure to give the brown colored crude product. The product was purified by silica gel column chromatography using ethyl acetate in pet ether as an eluant to afford 89A (4 g, 16.19 mmol, 64.8 % yield) as a off- white semi solid. NMR (400 MHz, CDC13) d 7.89-7.93 (m, 1H), 7.54-7.59 (m, 1H), 7.39-7.50 (m, 1H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Bromo-4-fluorobenzonitrile, and friends who are interested can also refer to it.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; BALOG, James Aaron; MARKWALDER, Jay A.; SHAN, Weifang; WILLIAMS, David K.; NARA, Susheel Jethanand; ROY, Saumya; THANGAVEL, Soodamani; CHERUKU, Srinivas; SISTLA, Ramesh Kumar; (230 pag.)WO2020/23355; (2020); A1;,
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Synthetic Route of 1114546-30-3,Some common heterocyclic compound, 1114546-30-3, name is 4-Bromo-2-fluoro-3-methylbenzonitrile, 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.

A mixture of 4-bromo-2-fluoro-3- methylbenzonitrile (7.0 g, 32.7 mmol), potassium vinyltrifluoroborate (5.3 g, 39.3 mmol), Pd(dppf)Cl2 (0.5 g, 0.7 mmol) and TEA (30 mL) in EtOH (70 mL) was refiuxed under Ar for 4 hours. After being cooled to room temperature, the reaction mixture was concentrated and the residue was purified by column chromatography (petrol ether : EtOAc = 10 : 1) to afford 2- fluoro-3-methyl-4-vinylbenzonitrile as a white solid.

The synthetic route of 1114546-30-3 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 96606-37-0, These common heterocyclic compound, 96606-37-0, name is 2,4,6-Trifluorobenzonitrile, 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 analogy to GP 2, 1 g of 2,4,6-trifluoro-benzonitrile (6.37 mmol; 1 eq.; commercially available) and 2.26 g 2-fluoro-4-iodo-benzenamine (9.55 mmol, 1.5 eq; commercially available) were dissolved in 100 ml of THF. The mixture was cooled to -65 C; 2.14 g of potassium tert-butoxide (19.1 mmol, 3 eq; commercially available) were added. The mixture was stirred for 35 min at this temperature and another 21 h at RT. The mixture was stirred into 120 ml of ice water and extracted three times with ethyl acetate (100 ml each). The combined organic layers were washed with brine, dryed over sodium sulfate and concentrated to afford 4.137 g of crude product. Purification was achieved by flash chromatography (hexane/ethyl acetate) to afford 646 mg (27.13% yield; 1.73 mmol) of the target compound.

The synthetic route of 96606-37-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BAYER SCHERING PHARMA AKTIENGESELLSCHAFT; BAYER HEALTHCARE AG; WO2008/138639; (2008); A1;,
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Reference of 501-00-8, 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. 501-00-8, name is 2-(3-Fluorophenyl)acetonitrile belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

2-(3-fluorophenyl)acetonitrile (6.000 g, 44.398 mmol) and sodium hydride (2.344 g, 97.676 mmol) in N,N-dimethylformamide (200 mL) at 0 C to this mixture 1,3-dibromopropane (4.504 mL, 44.398 mmol) was added and after stirring at 50 C for 17 hours, the temperature was lowered to room temperature, and a saturated sodium bicarbonate aqueous solution (10 mL) was added to the reaction mixture at 0 C and stirred for 10 minutes to complete the reaction. The solvent was removed from the reaction mixture under reduced pressure, the obtained concentrate was poured into water and extracted with hexane. The organic layer was washed with a saturated aqueous sodium chloride solution, and water was removed with anhydrous magnesium sulfate, followed by filtration and concentration under reduced pressure. The concentrate was purified by column chromatography (SiO2, 40 g cartridge; ethyl acetate/hexane=0% to 10%) and concentrated to give the title compound (4.270 g, 54.9%) as a colorless oil.

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, 2-(3-Fluorophenyl)acetonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Chong Kun Dang Co., Ltd.; Kim, Yoon Tae; Lee, Chang Sik; Oh, Jung Taek; Song, Hey Sung; Choe, Jin; Lee, Jae Young; (210 pag.)KR2017/43091; (2017); A;,
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Electric Literature of 16588-02-6, A common heterocyclic compound, 16588-02-6, name is 2-Chloro-5-nitrobenzonitrile, molecular formula is C7H3ClN2O2, 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.

1st Step Hydrazine monohydrate (4.87 ml) was added to an EtOH (19 ml) solution containing 2-chloro-5-nitrobenzonitrile (1.83 g), followed by stirring for 0.5 hour under ice cooling. Water was added to the reaction solution, and a solid precipitate was collected by filtration and washed with IPE and ethyl acetate. A red solid of 5-nitro-1H-indazol-3-amine (1.45 g) was thus obtained. MS (ESI m/z): 179 (M+H)

The synthetic route of 16588-02-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; FUJIFILM Corporation; FUJIWARA, Hideyasu; MIZUMOTO, Shinsuke; KUBO, Yohei; NAKATA, Hiyoku; HAGIWARA, Shinji; BABA, Yasutaka; TAMURA, Takashi; KUNIYOSHI, Hidenobu; MASHIKO, Tomoyuki; YAMAMOTO, Mari; US2014/309225; (2014); 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. 4640-66-8, name is 4-Chlorophenacylcyanide, A new synthetic method of this compound is introduced below., HPLC of Formula: C9H6ClNO

with morpholine This substance has been prepared using morpholine as the activating partner (eg. WO 2015/156601, WO 2015/131113, Angewandte Chemie, International Edition (2013), 52, 14060-14064, Journal of Biological Chemistry (2012), 287, 28840-28851, WO2011/143660, Nature (2010), 468, 1067-1073 & US 6323214) or with diethylamine (WO 2009/063301). In all reports, the product was purified by chromatography followed by recrystallization and no mention of the ethyl-isomer as side product has been recorded ever anywhere.Purification via oxalate saltCrude aminothiophene (5.0 g, 19 mmol) and oxalic acid (1.7 g, 1 eq.) were taken up in methanol (50 ml). The light orange suspension was heated to reflux creating a dark red solution which then was cooled to ambient temperature. The brown suspension that formed was evaporated on a rotovap at 45 C/250-25 mb and the crude oxalate salt dried for 4 h at 45 C/25 mbar providing a yellow-orange crystalline solid (6.2 g, GC: 87% product, 13% ethyl isomer). a) The oxalate salt (3.0 g) was taken up in acetonitrile (30 ml, lOx v/w) and the brown suspension was heated to reflux. The red solution produced was cooled and stirred at 25 C/1 h. A brown suspension arose which was filtered and the purified product was washed with dichloromethane (4 ml). The salt recovered was dried at 45 C/25 mb for 3 h and the filtrate evaporated.Yield: 1.4 g yellow solid GC (area): 99% product, 1% ethyl isomer

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; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; BLISS, Fritz; DU, Xiaohua; HE, Dawei; HILDBRAND, Stefan; SPURR, Paul; YE, Wenfa; ZHENG, Jianbing; (38 pag.)WO2018/109053; (2018); A1;,
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Application of 873697-68-8, 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. 873697-68-8, name is 3-Amino-2-fluorobenzonitrile belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

Example 3 Step 2. A solution of 3B in dichloromethane (about 1.5 M 3B in DCM) at RT under nitrogen mixture was cooled to ~0C, and 2.0 eq of IM diisobutyllithiumaluminum hydride (DIBAlH) in DCM was added drop wise over -3.5 hours, maintaining an internal reaction temperature < 00C. Upon completion of the DiBAlH addition, the reaction mixture was added dropwise with vigorous stirring to a cooled solution (-00C) of 40 volumes of 15% Rochelle salt and 10 volumes of DCM, maintaining an internal reaction temperature below 100C. The flask was rinsed with 10 volumes of DCM and the mixture was allowed to warm to room temperature and stirred for 4 hours. The layers were separated, and the aqueous layers were back extracted with 20 volumes of DCM. The combined organic layers were washed with 20 volumes of water. The organic layer was dried over sodium sulfate and concentrated to afford a brown foam, which was dried under vacuum (-30 in Hg) at RT to afford 3C (92% yield). Example 3 Step 3A/B. A solution 1 eq of 3C, tetrahydrofuran (about 1.4 M 3C in THF) and 1.05 eq of methyl piperazine-1-carboxylate and was allowed to stir at ambient temperature for 3 hours. To the reaction mixture was added 1.5 eq of sodium triacetoxyborohydride portionwise over -40 min, maintaining an internal reaction temperature below 45C. The reaction mixture was stirred overnight at room temperature. To the reaction mixture was added 5 volumes of water dropwise, over 1 hour, maintaining an internal reaction temperature below 300C. Ethyl acetate (EtOAc, 5 volumes) was then added, and the layers were separated. The aqueous layers were back extracted with 5 volumes of EtOAc. The combined organic layers were washed with saturated sodium bicarbonate and solid sodium bicarbonate was added as needed to bring the pH to 8 (pHydrion papers). The layers were separated, and the organic layer was washed with 5 volumes of brine. The organic layer was dried over sodium sulfate and activated carbon was added in the drying step. The organics were filtered through celite and the celite pad was rinsed 4 times with EtOAc. The organics were concentrated and dried overnight on the rotavap (~30 in Hg at RT) to afford an amber-brown oil. Step 3C. All calculations are based on the amount of 3C (R= O).[0146] To 3 volumes of methanol (based on 3C, R=O)under N2 over an an ice/brine/acetone bathwas added3 eq of acetyl chloride dropwise over 3 hours, maintaining an internal reaction temperature below 00C. The solution was then stirred for an additional 1 hour below 00C. A solution of 1.0 eq of unpurified 3D (from Steps 3 A/3B above) in MeOH (about 3.6 M based on 3C, R=O) was added dropwise over 30 min, maintaining an internal reaction temperature below 15C..The reaction was allowed to warm to room temperature overnight. The solids were filtered the next day and rinsed with 2x 0.5 volumes of MeOH, 5 volumes of 1:1 rerf-butyl methyl ether (MTBE):MeOH, and 5 volumes of MTBE.[0147] The solids were then taken up in 5 volumes of EtOAc and saturated sodium bicarbonate and solid sodium bicarbonate were added as needed to bring the pH of the aqueous layer to 8 (pHydrion papers). The layers were separated, and the aqueous layer was extracted with 5 volumes of EtOAc. The combined organic layers were washed with 5 volumes of brine, dried over sodium sulfate, and concentrated to afford a pale orange solid which was dried under vacuum (-30 in Hg) at ~40C to afford 3D (50% yield). 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-Amino-2-fluorobenzonitrile, other downstream synthetic routes, hurry up and to see. Reference:
Patent; CYTOKINETICS, INC.; WO2007/78839; (2007); A2;,
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Synthetic Route of 103146-25-4, These common heterocyclic compound, 103146-25-4, name is 4-(4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile, 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.

10.0g of 4-(4-fluoro-benzoyl)-3-hydroxymethyl-benzonitrile (MW: 255.25, assay: 96.7%; 37.9mmol) are dissolved in 14OmL of toluene. 7.77g of (S)-2-lambda/,lambda/-dimethylaminophenylethanol (MW: 165.24, 47.0mmol, 1.24 eq.) and 2.51g of methylboronic acid (MW: 59.86, assay: 98%, 41.1mmol, 1.08eq.) are added. The solution becomes slightly turbid and drops of water are rapidly formed. The mixture is heated to 500C. At reduced pressure (~60-70mbar) -10OmL of toluene / water are carefully removed. 10OmL of toluene are added and -10OmL of toluene / water are removed. 12OmL of toluene are added and about -2OmL of toluene / water are removed to get a solution of mixed boronate (~80mmol) in about 25OmL of solvent. The water content is below 0.1% as determined by a Karl Fischer titration. The reaction is cooled to – 65C. Within about 10-20 minutes 38.OmL of a -2M solution of dimethylaminopropyl magnesiumchloride in THF (-2 eq.) are added. Thereby, the temperature does not exceed -500C. The solution is stirred for another 30 minutes. Reaction control is performed with HPLC (ee = 90%). After complete conversion (area% 4-(4-fluoro-benzoyl)-3-hydroxymethyl-benzonitrile <2%) the reaction is worked up.2OmL of water are and 35mL of 2M aqueous H2SO4 (70mmol) are added to get a pH of -1.5 in the aqueous layer. After phase separation, the organic layer is washed once with 2OmL water, adjusted to pH 1 with 2M aqueous H2SO4. 15OmL of CH2CI2 are added to the combined aqueous layers. 7M aqueous NH3 is now added (29mL) until a pH of -9.0 is reached. After phase separation the aqueous layer is washed twice with 25mL of MED (at pH 9.0). The combined CH2CI2 layers are washed with 15mL of water. 7OmL of H2O are added. 10.7mL of 2M aqueous H2SO4 are added to adjust the pH to 6.4. After stirring for 10 minutes the layers are separated (pH 6.4). 35mL of water are added to the CH2CI2 layer. Addition of 1.5mL of 2M aqueous H2SO4 gives a pH of 6.4. After stirring for 10 minutes the layers are separated. 8OmL of CH2CI2 are added to the combined aqueous layers. Addition of 2mL of 7M aqueous RG/G-50021-BCK9987NH3 gives a pH of 6.4 (after equilibration). The layers are separated. The combined organic layers are washed with 2OmL of water. The layers are separated. The combined CH2CI2 layer contains the enantiomerically enriched diol. The combined aqueous layer contains -90% of the chiral auxiliary. 20OmL of CH2Cl2 are removed. 6OmL of 2-propanol are added. 3OmL of 2-propanol / CH2CI2 are removed under reduced pressure. 3OmL of 2-propanol are added to obtain -13g of CIT-DIOL in 6OmL of ISO. To this solution 6.59g of (+)-ditoluoyl tartaric acid (MW: 386.36; assay: 99%; 17.1mmol, 0.45eq.), dissolved in 42mL of 2-propanol and 8mL of CH2CI2, are added. The product starts to crystallize after 5 minutes (or immediately after seeding). The mixture is stirred for 90 minutes at 35C, for 10 minutes at 600C and than slowly cooled down to room temperature (within ~5hours) and crystallized without stirring for 10 hours. The product is isolated by filtration to give 17.2g of S-CIT-DIOLlambda’ (+)-DTTA.lambda1 ISO.lambda1 H2O (yield: 81.0%; ee: 99.0%, assay: 61.0%) after drying for IOhours at 400C and 20mbar.

Statistics shows that 4-(4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile is playing an increasingly important role. we look forward to future research findings about 103146-25-4.

Reference:
Patent; SANDOZ AG; WO2007/82771; (2007); A1;,
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Some common heterocyclic compound, 143879-80-5, name is 2,3,4-Trifluorobenzonitrile, molecular formula is C7H2F3N, 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. name: 2,3,4-Trifluorobenzonitrile

Scheme 21[0368] To 2,3,4-trifluorobenzonitrile (265 mg, 1.68 mmol) in a flask, a solution of D- leucine amide hydrochloride (282 mg, 1.68 mmol) and DIEA (0.880 mL, 5.06 mmol) in DMSO (5 mL) was added. After being stirred at room temperature for 68 h, water and EtOAc were added. The organic phase was separated, washed with water, dried over Na2S04, concentrated in vacuo. The residue was purified by a silica gel column, eluted with 0-70% EtOAc in hexane to give (R)-2-(4-cyano-2,3-difluorophenylamino)-4-methylpentanamide (113 mg).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 143879-80-5, 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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