Author: Jessica.F

These common heterocyclic compound, 26487-67-2, name is 1-(2-Chloroethyl)azepane hydrochloride, 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. name: 1-(2-Chloroethyl)azepane hydrochloride

To a solution of 2,2-bis(4-hydroxyphenyl)methylenecyclohexane (23.3 mg, 83.1 mumol) in DMF (0.83 mL) at 0 ¡ãC was added 55percent sodium hydride (dispersion in paraffin liquid, 29.1 mg, 0.667 mmol). The reaction mixture was stirred for 30 min at 50 ¡ãC and then N-(2-chloroethyl)hexahydro-1H-azepine hydrochloride (54.5 mg, 0.275 mmol) was added in portions at room temperature. After the reaction mixture had been stirred for 4 h at 50 ¡ãC, saturated aqueous ammonium chloride was added at 0 ¡ãC. The mixture was extracted with dichloromethane and the organic layer was dried over sodium sulfate. After filtration of the mixture and evaporation of the solvent, the crude product was purified by thin layer chromatography on silica (eluant; ammoniacal chloroform/methanol = 15/1) to afford RID-F-S*16 (compound 14) (32.0 mg, 73percent) as a yellow oil

The synthetic route of 1-(2-Chloroethyl)azepane hydrochloride has been constantly updated, and we look forward to future research findings.

Reference:
Article; Hasegawa, Makoto; Yasuda, Yukari; Tanaka, Makoto; Nakata, Kenya; Umeda, Eri; Wang, Yanwen; Watanabe, Chihiro; Uetake, Shoko; Kunoh, Tatsuki; Shionyu, Masafumi; Sasaki, Ryuzo; Shiina, Isamu; Mizukami, Tamio; European Journal of Medicinal Chemistry; vol. 71; (2014); p. 290 – 305;,
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94-97-3, name is 5-Chloro-1H-benzo[d][1,2,3]triazole, 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. Formula: C6H4ClN3

General procedure: A typical procedure for the catalytic N-sulfonylation of benzotriazoles using I2 as catalyst includes: in EtOAc-H2O (10:1) mixture solvent (2 mL), benzotriazole 1a (0.3 mmol), sodium benzenesulfinate 2a (0.9 mmol), I2 (0.06 mmol) were added successively. The suspension mixture was vigorously stirred at room temperature for 3 h. Upon completion, the reaction was quenched by addition of sat. aq. Na2S2O3 (2 mL), basified with sat. aq. Na2CO3 (8 mL) and H2O (5 mL). The mixture was extracted with CH2Cl2 (3* 5 mL) and the combined organic phase was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was then purified by TLC technique (petroleum ether/ethyl acetate = 3:1, v/v) to furnish 1-phenylsulfonylbenzotriazole 3a [28] in 97% yield.

The synthetic route of 94-97-3 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Wu, Si-Xue; Zhang, Yi-Kun; Shi, Hong-Wei; Yan, Jie; Chinese Chemical Letters; vol. 27; 9; (2016); p. 1519 – 1522;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 110407-59-5, A common heterocyclic compound, 110407-59-5, name is 2-Chloro-4-fluorobromobenzene, molecular formula is C6H3BrClF, 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.

Step C: Preparation of a-(2-chloro-4-fluorophenyl)-2 -methyl- 1 -(2,4,6- trifluorophenyl)- lH-imidazole-5 -methanolTo a mixture of l-bromo-2-chloro-4-fluorobenzene (2.35 mL, 19.3 mmol) in tetrahydrofuran (15 mL) at -2 to -3 C was added isopropylmagnesium chloride lithium chloride (1.3 M in tetrahydrofuran, 15 mL, 19.5 mmol) dropwise over ten minutes. The reaction mixture was stirred for 1.5 h at 0 to 5 C, and then 2 -methyl- 1 -(2,4,6- trifluorophenyl)-lH-imidazole-5-carboxaldehyde (i.e. the product of Step B) (2.32 g, 9.65 mmol) in tetrahydrofuran (8 mL) was added dropwise over 10 minutes while maintaining the reaction temperature at about 0 to 5 C. After 1 h, saturated aqueous ammonium chloride solution (10 mL) was added dropwise to the reaction mixture, and the mixture was extracted with ethyl acetate (2 x 25 mL). The combined organic layers were washed with aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated under reduced pressure at 45 C until a slurry was obtained. Hexanes were added to the resulting slurry (with agitation) and the mixture was allowed to cool to ambient temperature (about 20 C). The resulting precipitate was collected on a sintered glass frit funnel, washed ethyl acetate/hexanes (1 : 1, 3 mL), and allowed to air dry to provide the title compound, a compound of the present invention, as a tan solid (1.866 g)..H NMR (DMSO- ) delta delta 7.5 (m, 3H), 7.38 (m, 1H), 7.20 (m, 1H), 6.43 (s, 1H), 5.96 (m, 1H), 5.64 (m, 1H), 2.05 (s, 3H).

The synthetic route of 110407-59-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; E. I. DU PONT DE NEMOURS AND COMPANY; LONG, Jeffrey, Keith; BEREZNAK, James, Francis; KAR, Moumita; TAGGI, Andrew, Edmund; CHEN, Yuzhong; WO2012/44650; (2012); A1;,
Chloride – Wikipedia,
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Application of 2613-34-5, 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. 2613-34-5 name is 3-Chloro-2,4-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.

Ethyl l-(2-ethoxy-2-oxo-acetyl)-2-methyl-piperidine-3-carboxylate was prepared from ethyl 2-methylpiperidine-3-carboxylate, similarly as described for methyl (2S,3S)-1- (2-ethoxy-2-oxo-acetyl)-2-methyl-pyrrolidine-3-carboxylate from methyl (2S,3S)-2- methylpyrrolidine-3-carboxylate. Compound 35 was prepared similarly as described for compound 33, starting from Ethyl l-(2-ethoxy-2-oxo-acetyl)-2-methyl-piperidine-3- carboxylate instead of methyl (2S,3S)-l-(2-ethoxy-2-oxo-acetyl)-2-methyl-pyrrolidine-3- carboxylate and using 3-chloro-2,4-difluoro-aniline instead of 3-chloro-4,5-difluoro- aniline. Compound 35 (550 mg) was separated in diastereoisomers 35a, 35b, 35c and 35d via Preparative SFC (Stationary phase: Chiralpak Daicel IC 20 x 250 mm, Mobile phase: C02, EtOH with 0.2% iPrNH2). Compound 35a ((2S,3S) or (2R,3R), first eluting on SFC, 70 mg), Method D, Rt = 1.86 min., m/z = 454.1 (M-H)”, Exact mass: 455.1. Compound 35b ((2S,3S) or (2R,3R), second eluting on SFC, 88 mg) Method D, Rt = 1.87 min., m/z = 454.1 (M-H)”, Exact mass: 455.1. Compound 35c ((2S,3R) or (2R,3S), third eluting on SFC, 86 mg), Method D, Rt = 1.89 min., m/z = 454.1 (M-H)”, Exact mass: 455.1. Compound 35d ((2S,3R) or (2R,3S), fourth eluting on SFC, 106 mg), Method D, Rt = 1.88 min., m/z = 454.1 (M-H)”, Exact mass: 455.1.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3-Chloro-2,4-difluoroaniline, and friends who are interested can also refer to it.

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;,
Chloride – Wikipedia,
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Application of 13726-14-2, These common heterocyclic compound, 13726-14-2, name is 4-Chloro-3-methoxyaniline, 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.

Ir (ppy) 3 (2 mg) and DMF (1 ml) were added to the reaction flask under nitrogen or argon atmosphere and then irradiated with a blue LED band (7 W) at room temperature until complete conversion of the trivalent iodine reagent was completed. 10 ml of a saturated aqueous Na2C03 solution was added thereto, and the mixture was extracted three times with ethyl acetate. The organic layer was washed once with saturated brine, and the organic layer was dried over anhydrous Na2S04. Column chromatography (eluent: petroleum ether 60-90: ethyl acetate = 20: 1-10: 1) afforded the product in a yield of 62%

The synthetic route of 13726-14-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Nanjing University; Zhu, ChengJian; Xie, jin; Xu, Pan; (13 pag.)CN103553857; (2016); B;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 61881-19-4, name is 2,2,2-Trifluoro-N-phenylacetimidoyl chloride, belongs to chlorides-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 61881-19-4, Product Details of 61881-19-4

To 6 (5.0 g, 5 mmol) and N-phenyl trifluoroacetimidoyl chloride (1.6 g, 7.5 mmol, 1.5 eq) in acetone (103.0 ml) was added K2CO3 (1.0 g, 7.5 mmol, 1.5 eq). The mixture was stirred at room temperature for 1 h. The reaction was monitored by TLC (hexane : ethyl acetate = 2:1) .The mixture was filtered, concentrated, and purified by silica gel column chromatography (hexane : ethyl acetate = 4:1) to obtain the 9 (5.7 g, 96%) as white solid. m. p.132 – 134 oC. [alpha]25D = – 213.6 (c = 1.00 in CHCl3).1H NMR (400 MHz, CDCl3) delta 8.49 – 6.58 (m, 36H), 6.28 (d, J = 10.5 Hz, 1H), 6.01 (d, J = 3.2 Hz, 1H), 5.93 (dd, J = 10.5, 3.4 Hz, 1H), 5.76 (s, 1H), 5.65 (dd, J = 10.5, 3.1 Hz, 1H), 4.98 (d, J = 8.9 Hz, 1H), 4.55 – 4.34 (m, 4H), 4.17 (d, J = 12.0 Hz, 1H), 3.98 (dd, J = 13.1, 1.8 Hz, 1H), 3.92 (d, J = 9.6 Hz, 1H), 1.75 (s, 3H). 13C NMR (100 MHz, CDCl3) delta 170.1-164.83 (C, C=O), 143.2 (C, N-C), 141.0 (F3CC=N), 133.6-128.1 (C, Ar), 124.9, 119.2,116.2 (q, CF3), 106.3, 99.1, 70.2, 69.9, 69.7, 69.1, 68.5, 66.8, 63.9, 63.3, 61.9, 58.3, 20.3. ESI-MS (m/z) : [M+Na]+ : calcd for C62H52F3NO18Na+ 1202.3029, found 1202.3028.

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, 2,2,2-Trifluoro-N-phenylacetimidoyl chloride, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Zhang, Hongliang; Wang, Hengtao; Xu, Qiulong; Lu, Rui; Cao, Yunhua; Wang, Zhefeng; Tang, Pingping; Lin, Feng; Li, Yingxia; Carbohydrate Research; vol. 448; (2017); p. 6 – 9;,
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. 7051-16-3, name is 1-Chloro-3,5-dimethoxybenzene belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. category: chlorides-buliding-blocks

3-Chloro-5-methoxy-phenol3-Chloro-5-methoxy-phenolSodium methanelhiolate (3.04 g, 43.37 mmol), was added to a solution of l-chloro-3.5- dimethoxy benzene (5.0 g, 28.96 mmol) in 20 ml of l-Methyl-2-Pyrrolidone and the reaction mixture was heated at 140 C for 2.5 h then stirred at room temperature over night. l-Methyl-2-pyrrolidone was removed under reduced pressure and the material partitioned between ethyl acetate/water/lN hydrochloric acid. The organic layer was washed twice with IN hydrochloric acid, brine, dried over sodium sulfate and solvent removed under reduced pressure to give a yellowish solid. The solid was purified by column chromatography (silica gel 60-120 mesh, 10:90 ethylacetate:hexane) to afford 3- Chloro-5-methoxy-phenol in 76.4 % yield.MS [M-H] 157.2, ? NMR (400 MHz, CDCI3) delta (ppm): 6.455-6.500 (d, 2H, J=I8.0 Hz), 6.291 (s, 1H), 4,978 (s, III), 3.767 (s, 3H).

The synthetic route of 7051-16-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; JUBILANT BIOSYS LTD.; SARMA, Pakala Kumara Savithru; ACHARYA, Vinod Parameshwaran; KASIBHATLA, Srinivas Rao; VISWANADHAN, Vellarkad Narayana; TIWARI, Atul; SINGHA, Rakesh Kumar; BISCHOFF, Alexander; (149 pag.)WO2012/90219; (2012); A2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Some common heterocyclic compound, 928782-97-2, name is 4-Chloro-2-(phenylethynyl)aniline, molecular formula is C14H10ClN, 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: 4-Chloro-2-(phenylethynyl)aniline

General procedure: The substituted 2-alkynylaniline (1.0 mmol) was dissolved in acetonitrile (5.0 mL) and stirred until the solution became homogeneous. To this solution, methyl vinyl ketone (1.5 mmol) followed by 20 mol % of PdCl2 (59-60%, 35 mg) was added under a nitrogen atmosphere, then heated to 60 C and monitored by TLC. After completion of the reaction, the mixture was cooled to room temperature and the acetonitrile was removed by vacuum evaporation. The resulting crude product was purified by column chromatography to afford the desired 2,3-disubstituted indoles. 1-(5-Chloro-2-phenyl-1H-indol-3-yl)pentan-3-one (3n) Yield: (300 mg, 96%); Colorless solid. Mp: 138-140 C. FT-IR (KBr) (nu/cm-1): 3370, 1711. 1H NMR (400 MHz, CDCl3) deltaH (ppm): 8.10 (br s, 1H), 7.55-7.53 (m, 3H), 7.47 (t, J=7.5 Hz, 2H), 7.40-7.36 (m, 1H), 7.27 (d, J=8.56 Hz, 1H), 7.15 (dd, J=8.5, 1.9 Hz, 1H), 3.15-3.11 (m, 2H), 2.77-2.73 (m, 2H), 2.39 (q, J=7.3 Hz, 2H), 1.03 (t, J=7.3 Hz, 3H). 13C NMR (100 MHz, CDCl3) deltaC (ppm): 211.1, 136.1, 134.4, 132.7, 130.1, 129.2, 128.3, 128.1, 125.5, 122.7, 118.6, 112.1, 111.9, 43.1, 36.2, 18.9, 7.9. LRMS (EI) (m/z) (relative intensity): 311 (M+, 50), 328 (100); HRMS calcd for C19H18Cl1O1N1 (M+): 311.1077, found 311.1086.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 928782-97-2, its application will become more common.

Reference:
Article; Janreddy, Donala; Kavala, Veerababurao; Kuo, Chun-Wei; Kuo, Ting-Shen; He, Chiu-Hui; Yao, Ching-Fa; Tetrahedron; vol. 69; 15; (2013); p. 3323 – 3330;,
Chloride – Wikipedia,
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Some common heterocyclic compound, 1871-57-4, name is 3-Chloro-2-chloromethyl-1-propene, molecular formula is C4H6Cl2, 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. COA of Formula: C4H6Cl2

To a solution of 0.235 g of (+)-(1-Benzyloxycarbamoyl-but-3-enyl)-carbamic acid tert-butyl ester (9a) in 8 mL of tetrahydrofuran was added 0.635 g of cesium carbonate. The reaction was heated to 60oC for 60 minutes, and then 1 mL of 2-chloro-3-methallyl chloride was added. The reaction was heated for an additional 20 hours. The reaction was then cooled, quenched with NH4Cl(aq.) solution, and extracted with ethyl acetate. The organic layers were washed with NH4Cl(aq.) and NaCl(aq.) solutions. The aqueous layers were re-extratced with ethyl acetate, and the organic layers combined and dried over Na2SO4(s). Filtration and solvent removal gave a white, oily solid. Column chromatography (hexanes/ethyl acetate gadiant) on silica gel, followed by fraction combination, and solvent removal gave 170 mg of a white solid (57% yield). 1H NMR (CDCl3): d 2.36 (quint, 1H, J=7 Hz), 2.48 (quint, 1H, J=7 Hz), 4.06 (d, 2H, J=4 Hz), 4.12 (m, 1H), 4.68 (m, 1H), 4.88 (bs, 1H), 4.99 (m, 2H), 5.13 (m, 1H), 5.26 (m, 2H), 5.72 (m, 1H), 7.4 (m, 5H); MS: 839 (2M+Na), 431 (M+Na).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1871-57-4, its application will become more common.

Reference:
Article; Wilson, Lawrence J.; Wang, Bingbing; Yang, Shyh-Ming; Scannevin, Robert H.; Burke, Sharon L.; Karnachi, Prabha; Rhodes, Kenneth J.; Murray, William V.; Bioorganic and Medicinal Chemistry Letters; vol. 21; 21; (2011); p. 6485 – 6490;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

These common heterocyclic compound, 933190-51-3, name is 8-Bromo-6-chloroimidazo[1,2-b]pyridazine, 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. Safety of 8-Bromo-6-chloroimidazo[1,2-b]pyridazine

A mixture of 8-bromo-6-chloroimidazo[l,2-b]pyridazine (573 mg, 2.47 mmol), 6-(3-tert- butylpyrrolidin-l-yl)pyridin-2-amine (540 mg, 2.47 mmol), Pd2(dba)3 (142 mg, 0.25 mmol), BINAP (307 mg, 0.50 mmol), Cs2C03 (2.4 g, 7.41 mmol) and dioxane (20 mL) was heated to reflux with stirring for 15 h under N2. The solvent was removed in vacuo and the resulting mixture was purified by chromatography (silica gel, 200 – 300 mesh, dichloromethane : MeOH = 50 : 1) to give N-(6-(3-tert-butylpyrrolidin-l-yl)pyridin-2-yl)-6-chloroimidazo [l,2-b]pyridazin- 8-amine (400 mg, crude) as a brown oil. LC-MS: [M+H]+, 371.1 , tR = 2.23 min.

The synthetic route of 8-Bromo-6-chloroimidazo[1,2-b]pyridazine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HERMANN, Johannes Cornelius; KUGLSTATTER, Andreas; LUCAS, Matthew C.; PADILLA, Fernando; WANNER, Jutta; ZHANG, Xiaohu; WO2013/64445; (2013); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics