Day: March 18, 2022

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.1059630-08-8,(4aS,9bR)-Ethyl 6-bromo-3,4,4a,5-tetrahydro-1H-pyrido[4,3-b]indole-2(9bH)-carboxylate,as a common compound, the synthetic route is as follows.

Example 5-A: Production of (6bR,10aS)-ethyI 2,3,6b,9,10,10a-hexahydro-2-oxo-lH- pyrido [3 ‘,4’ :4,5]-py rrolo [1 ,2,3-de] quinoxaline-8-carboxy late; Alternative to Example 5 above, (6bR, 1 OaS)-ethyl 3,6b,9, 10, 1 Oa- hexahydro-3 -methyl-2-oxo- 1 H-pyrido [3 ‘ ,4 ‘ :4,5]-pyrrolo [ 1 ,2,3 -de]quinoxaline-8- carboxylate may also be made in a one pot method starting from Compound of Formula ID. A 2 liter 4 neck round bottom flask is equipped with a mechanical stirrer, reflux condenser, N2 inlet, teflon covered K-type temperature probe with a controller, and a heating mantle. To the flask is charged (4aS,9bR)-ethyl 6-bromo-3,4,4a,5-tetrahydro- lH-pyrido[4,3-b]indole-2(9bH)-carboxylate (250 g, 769 mmol), chloroacetamide (124 g, 1153 mmol, 1.5 equiv), potassium iodide (191.5 g, 1160 mmol, 1.5 equiv), diisopropyl ethylamine (266 mL, 1531 mmol, 2.0 equiv), and dioxane (625 mL). The reaction is heated to reflux temperature of about 103 0C until less than 3% of the starting substrate is observed by HPLC (about 48 hours). Additional charge of N- methyl chloroacetamide and diisopropyl ethylamine maybe necessary. The reaction is then cooled to ca. 80 0C, and at this temperature copper iodide (29.2 g, 153.8 mmol, 0.2 equiv), potassium carbonate (232.5 g, 1682 mmol, 2.2 equiv), dimethylethylene diamine (49.6 mL, 461 mmol, 0.6 equiv), and additional dioxane (375 mL) is added. The reaction is then re-heated to reflux and is monitored by HPLC. Reflux occurs at ca. 103 0C. The reaction is monitored by HPLC.; Example 6-A: Production of (6bR,10aS)-ethyl 2,3,6b,9,10,10a-hexahydro-3-methyl- 2-oxo-lH-pyrido[3%4′:4,5]-pyrrolo[l,2,3-de]quinoxaline-8-carboxylate; Alternative to Example 6 above, (6bR, 1 OaS)-ethyl 3,6b,9, 10, 1 Oa- hexahydro-3-methyl-2-oxo-lH-pyrido[3′,4’:4,5]-pyrrolo[l,2,3-de]quinoxaline-8- carboxylate may also be made in a one pot method starting from Compound of Formula ID. A 2 liter 4 neck round bottom flask is equipped with a mechanical stirrer, reflux condenser, N2 inlet, teflon covered K-type temperature probe with a controller, and a heating mantle. To the flask is charged (4aS,9bR)-ethyl 6-bromo-3,4,4a,5-tetrahydro- lH-pyrido[4,3-b]indole-2(9bH)-carboxylate (250 g, 769 mmol), N-methyl chloroacetamide (124 g, 1153 mmol, 1.5 equiv), potassium iodide (191.5 g, 1160 mmol, 1.5 equiv), diisopropyl ethylamine (266 mL, 1531 mmol, 2.0 equiv), and dioxane (625 mL). The reaction is heated to reflux temperature of about 103 0C until less than 3% of the starting substrate is observed by HPLC (about 48 hours). Additional charge of N- methyl chloroacetamide and diisopropyl ethylamine maybe necessary. The reaction is then cooled to ca. 80 0C, and at this temperature copper iodide (29.2 g, 153.8 mmol, 0.2 equiv), potassium carbonate (232.5 g, 1682 mmol, 2.2 equiv), dimethylethylene diamine (49.6 mL, 461 mmol, 0.6 equiv), and additional dioxane (375 mL) is added. The reaction is then re-heated to reflux and is monitored by HPLC. Reflux occurs at ca. 103 0C. The reaction is monitored by HPLC.[0090] When complete, the reaction is cooled to ca. 40 0C and poured onto a plug of flash-grade silica gel (625 g, 2.5 g/g). It is eluted (under vacuum) with 6.25 L of ethyl acetate. The eluent is concentrated to a solid residue (320 gm), and then is dissolved in hot ethanol (800 ml). This mixture is allowed to cool to ambient temperature and stirred overnight. The next day it is cooled to 0-50C, aged for Ih and filtered. The cake is washed with cold ethanol (150 ml) and allowed to air dry to afford 170 grams (70%) of product as a white solid which is >99A% pure by HPLC. HPLC 10:90 to 90:10 CH3CN:H2O over 15 min. Hold at 90:10 for 2 min, 0.025% TFA Buffer, 1.5 mL/min, UV at 220 run, Phenomenex Jupiter Cl 8 column 4.6 mm x 250 mm. The product is 75A% pure by LC/MS in the total ion chromatogram. 1H-NMR (300MHz, CDCl3) 1.28(t, J= 6.9Hz, 3H), 1.86-1.96(m, 2H), 2.72(br, IH), 3.09-3.48(m, 7H), 3.86- 4.21(m, 5H), 6.75(dd, J= 1.2, 7.8Hz, IH), 6.82(t, J= 7.8Hz, IH), 6.90(dd, J= 1.2, 7.2Hz, IH).

1059630-08-8, The synthetic route of 1059630-08-8 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; INTRA-CELLULAR THERAPIES, INC.; WO2008/112280; (2008); A1;,
Indole alkaloid derivatives as building blocks of natural products from?Bacillus thuringiensis?and?Bacillus velezensis?and their antibacterial and antifungal activity study
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.393553-57-6,6-Bromo-4-methoxy-1H-indole,as a common compound, the synthetic route is as follows.

NaH (96mg, 4mmol) was suspended in 7mL DMF in a round bottom flask and cooled to 0C. 6-bromo-4-methoxy-1H-indole (0.75g, 3.3mmol) was added dropwise as a solution in DMF (ImL). Ethyl iodide (0.28mL, 3.5mmol) was added dropwise and the reaction mixture was stirred for 10 min. Volatiles were removed under reduced pressure and the residue partitioned between DCM and water. The aqueous layer was extracted with DCM and the combined organics layers were dried over MgSO4, filtered, and evaporated to give a red oil. The resulting residue was purified on silica gel column chromatography eluting with hexanes/ethyl acetate (0-10%) to afford pure 36-2 (584mg, 70%) as a white solid., 393553-57-6

As the paragraph descriping shows that 393553-57-6 is playing an increasingly important role.

Reference：
Patent; GALENEA CORPORATION; ELDER, Amy; HARRIMAN, Geraldine; LEIT, Silvana; LI, Jie; SARD, Howard; ZHANG, Yiliang; WILSON, Doug; WO2011/19738; (2011); A1;,
Indole alkaloid derivatives as building blocks of natural products from?Bacillus thuringiensis?and?Bacillus velezensis?and their antibacterial and antifungal activity study
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

900514-08-1,900514-08-1, 5-Chloro-3-iodo-7-azaindole is a indole-building-block compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

A mixture solution of 5-chloro-3-iodo-1H-pyrrolo [2 3-b] pyridine (8 g 28.7 mmol) cesium carbonate (18.7 g 57.5 mmol) and 4-toluenesulfonyl chloride (8.19 g 43.1 mmol) in DMF (80 mL) was stirred at room temperature for 4 h. Afterwards the mixture was poured into water and the suspension was filtered. The crude title compound (8.7 g 70yield) was collected as filter cake. MS 433.1 (M+1)+. It was used direclty in the next step without further purification.

The synthetic route of 900514-08-1 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; SAVIRA PHARMACEUTICALS GMBH; EUROPEAN MOLECULAR BIOLOGY LABORATORY; TAN, Xuefei; ZBINDEN, Katrin Groebke; KUHN, Bernd; WANG, Lisha; LIU, Yongfu; WU, Jun; SHEN, Hong; SHI, Tianlai; (174 pag.)WO2017/133664; (2017); A1;,
Indole alkaloid derivatives as building blocks of natural products from?Bacillus thuringiensis?and?Bacillus velezensis?and their antibacterial and antifungal activity study
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.2795-41-7,6-Fluoroindole-3-carboxaldehyde,as a common compound, the synthetic route is as follows.

Compound 1b (1.0 mmol, 177 mg) was added to a 25 mL sealed tube.Compound 2h (0.5 mmol, 81.6 mg), iodine simple substance (0.5 mmol, 127 mg),Pyridine (0.5 mmol, 39.6 mg) and 1,4-dioxane (2 mL),The reaction was then stirred in an oil bath at 110 C for 12 h. The reaction was quenched by the addition of 50 mL of water and extracted with ethyl acetate (50 mL×3).Washing with 10% Na2S2O3 solution and saturated brine,Dry over anhydrous sodium sulfate. Filter, spin dry,Separated by silica gel column(petroleum ether/ethyl acetate = 10/1, v/v)The product was obtained as a white solid 3s (123.7 mg, 68%)., 2795-41-7

The synthetic route of 2795-41-7 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Xinxiang Medical University; Gao Qinghe; Liu Xingxia; Yuan Huan; Wang Yakun; Tong Peiyuan; Shen Haotian; Zhang Zhiang; Zhang Weirong; Zhang Jixia; (22 pag.)CN108976198; (2018); A;,
Indole alkaloid derivatives as building blocks of natural products from?Bacillus thuringiensis?and?Bacillus velezensis?and their antibacterial and antifungal activity study
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

434958-85-7,With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.434958-85-7,N-Boc-5-Hydroxyindole,as a common compound, the synthetic route is as follows.

2 g (8.6 mmol) of 5-hydroxy-1-tert-butyl ester-1H-indole (a) was dissolved in 5 ml of DMF.3.56 g (25.8 mmol) of potassium carbonate was added and stirred at room temperature for 10 minutes.Then 14.3 ml (172 mmol) of 1-bromo-2-chloroethane was added.After stirring at 100 C for 10 hours, it was diluted with water and extracted with DCM.Wash with saturated sodium chloride, dry over anhydrous sodium sulfate, concentrate under reduced pressure, and thenPE/EA=200:1 gave a white solid1.3 g, yield 52%.

As the paragraph descriping shows that 434958-85-7 is playing an increasingly important role.

Reference：
Patent; Tianjin University of Science and Technology; Yu Peng; Guo Na; Lv Hongbin; Fu Ying; Teng Yuou; Wang Dong; (32 pag.)CN110229091; (2019); A;,
Indole alkaloid derivatives as building blocks of natural products from?Bacillus thuringiensis?and?Bacillus velezensis?and their antibacterial and antifungal activity study
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.101861-63-6,4,6-Dichloroindole-2-carboxylic acid,as a common compound, the synthetic route is as follows.

Step 1 – Methyl 4,6-dichloro-1-methyl-indole-2-carboxylate (0369) [00268] To a mixture of 4,6-dichloro-1H-indole-2-carboxylic acid (950 mg, 4.13 mmol, CAS101861-63-6) in N,N-dimethylformamide (10 mL) was added potassium carbonate (2.28 g, 16.5 mmol). Iodomethane (3.52 g, 24.8 mmol) was added to the mixture dropwise. Then the mixture was stirred at 60 C for 12 hrs. On completion, the mixture was quenched with water (30 mL). The mixture was extracted with ethyl acetate (2 x 20 mL). The organic layers were dried with anhydrous sodium sulfate, filtrated, and concentrated in vacuo to give the title compound. 1H NMR (400MHz, CDCl3) delta = 7.34 (s, 1H), 7.30 (s, 1H), 7.17 (d, J = 1.3 Hz, 1H), 4.15 (s, 3H), 4.01 (s, 3H)., 101861-63-6

101861-63-6 4,6-Dichloroindole-2-carboxylic acid 127988, aindole-building-block compound, is more and more widely used in various fields.

Reference：
Patent; RAZE THERAPEUTICS, INC.; MAINOLFI, Nello; MOYER, Mikel P.; SAIAH, Eddine; (264 pag.)WO2017/156181; (2017); A1;,
Indole alkaloid derivatives as building blocks of natural products from?Bacillus thuringiensis?and?Bacillus velezensis?and their antibacterial and antifungal activity study
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.192189-07-4,tert-Butyl 3-iodo-1H-indole-1-carboxylate,as a common compound, the synthetic route is as follows.

Triethyl borate (2.92 g, 20 mmol) was dissolved in tetrahydrofuran (20 mL) Cooled to -78 C, n-butyllithium (2.4 mol / L, 8.33 mL, 20 mmol) Stirred for half an hour, tert-butyl 3-iodo-lH-indole-1-carboxylate (3.43 g, LOmmol), slowly rose to room temperature, stirred for 2 hours, TLC detection of raw materials disappeared. Add water, ethyl acetate extraction, combined organic phase, Dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation to give crude (2.61 g) Without purification directly for the next step, 192189-07-4

The synthetic route of 192189-07-4 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Shandong Xuanzhu Pharmaceutical Technology Co., Ltd.; Wu Yongqian; (29 pag.)CN104876914; (2017); B;,
Indole alkaloid derivatives as building blocks of natural products from?Bacillus thuringiensis?and?Bacillus velezensis?and their antibacterial and antifungal activity study
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.1265231-91-1,3-(Dimethylamino)-2-(1-(phenylsulfonyl)-1H-indole-2-carbonyl)acrylonitrile,as a common compound, the synthetic route is as follows.

2-(1-Fluorocyclopropyl)-5-hydrazinyl-1H-benzo[d]imidazole dihydrochloride 10d (706mg, 2.5 3mmol) and (E)-3-(dimethylamino)-2-(1-(phenylsulfonyl)-1H-indole-2-carbonyl)acrylonitrile 1f (959mg, 2.53mmol, prepared according to the published patent application ) were suspended in 13mL of absolute ethanol, the reaction solution was refluxed for 4 hours. The reaction solution was cooled down to room temperature, solid precipitated. The solution was subjected to suction filtration, the filter cake was washed with ethanol (15mL*3) then was subjected to infrared drying to obtain (5-amino-1-(2-(1-fluoropropyl)-1H-benzo[d]imidazol-5-yl)-1H-pyrazol-4-yl)(1-(phenylsulfonyl)-1H-indol-2-yl)methanone 10e (493mg, black solid), yield: 36%. MS m / z (ESI): 540.8 [M + 1]

1265231-91-1, The synthetic route of 1265231-91-1 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Zhejiang Hisun Pharmaceutical Co., Ltd; CHEN, Lei; GUAN, Dongliang; BAI, Hua; YAN, Xing; MIAO, Shuai; ZHU, Songsong; (54 pag.)EP3339305; (2018); A1;,
Indole alkaloid derivatives as building blocks of natural products from?Bacillus thuringiensis?and?Bacillus velezensis?and their antibacterial and antifungal activity study
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.31241-19-7,5-Methoxy-2,3,3-trimethyl-3H-indole,as a common compound, the synthetic route is as follows.,31241-19-7

5-Methoxy-2,3,3-trimethyl-3H-indole 12 g (0,063 mol) was dissolved in toluene (20 ml), condenser was attached to the flask and acethyl chloride 9 ml (p=1.104 g/Ml, 9,94 g) was added dropwise. After cooling the mixture to ambient temperature, the mixture was stored at 5 C. for 12 h. Formed crystals were filtered, washed with acetone and cold ether. Yield is 6.6 g of indolium chloride (46.12%) as yellowish crystals. M.p. 201-203 C. 1H NMR (400 MHz, DMSO-D6): delta 1.45 (s, 6H, 2*CH3), 2.62 (s, 3H, 2-CH3), 3.82 (s, 3H, 5-OCH3), 7.02 (dd, J=8.8 Hz, J=2.4 Hz, 1H, 6-H), 7.37 (d, J=2.4 Hz, 1H, 4-H), 7.54 (d, J=8.4 Hz, 1H, 7-H). 13C BMR (100 MHz, DMSO-D6): delta 14.3, 22.0 (2*C), 53.8, 55.9, 109.4, 113.9, 117.2, 134.9, 145.3, 159.7, 193.0. IR (KBr), nu (cm-1): 3134 (N-H), 3021, 2973, 1623, 1479, 1404, 1289, 1022, 797.

The synthetic route of 31241-19-7 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; KAUNAS UNIVERDITY OF TECHNOLOGY; SACKUS, Algirdas; Marynaitis, Vytas; Krikstolaityt, Sonata; Ragaite, Greta; Vengris, Mikas; (12 pag.)US2017/355709; (2017); A1;,
Indole alkaloid derivatives as building blocks of natural products from?Bacillus thuringiensis?and?Bacillus velezensis?and their antibacterial and antifungal activity study
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

2795-41-7, 6-Fluoroindole-3-carboxaldehyde is a indole-building-block compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

General procedure: To a stirred solution of ketone 9b (50 mg, 0.34 mmol) andaldehyde (0.34 mmol) in anhydrous EtOH, piperidine (144.9 mg,1.72 mmol) was slowly added. After stirring for 10 h at 80 C, thereaction mixture was concentrated and extracted with CH2Cl2(3 20 mL). The combined organic layers were then washed withbrine, dried over anhydrous Na2SO4, and concentrated in vacuo toprovide the crude product, which was purified by column chromatography with petroleum/ethyl acetate (4:1) to give thecorresponding pure compounds 18a-i., 2795-41-7

The synthetic route of 2795-41-7 has been constantly updated, and we look forward to future research findings.

Reference：
Article; Xu, Feijie; Li, Wenlong; Shuai, Wen; Yang, Limei; Bi, Yi; Ma, Cong; Yao, Hequan; Xu, Shengtao; Zhu, Zheying; Xu, Jinyi; European Journal of Medicinal Chemistry; vol. 173; (2019); p. 1 – 14;,
Indole alkaloid derivatives as building blocks of natural products from?Bacillus thuringiensis?and?Bacillus velezensis?and their antibacterial and antifungal activity study
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles