Month: March 2022

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.288385-93-3,4-Fluoro-5-methoxy-2-methyl-1H-indole,as a common compound, the synthetic route is as follows.,288385-93-3

To a solution of 4-fluoro-5-methoxy-2-methylindole (709 mg, 3.95 mmol) in methylene chloride (9 ml) cooled at -30 C. was added a solution of boron tribromide (2.18 g, 8.7 mmol) in methylene chloride (1 ml). After stirring for 1 hour at ambient temperature, the mixture was poured onto water and was diluted with methylene chloride. The pH of the aqueous layer was adjusted to 6. The organic layer was separated, washed with water, brine, dried (MgSO4) and evaporated. The residue was purified by column chromatography, eluding with ethyl acetate/petroleum ether (3/7) to give 4-fluoro-5-hydroxy-2-methylindole (461 mg, 70%). MS-ESI: 166 [MH]+ 1H NMR Spectrum: (DMSOd6) 2.35 (s, 3H); 6.05 (s, 1H); 6.65 (dd, 1H); 6.9 (d, 1H); 8.75 (s, 1H); 10.9 (s, 1H) 13C NMR Spectrum: (DMSOd6) 13.5; 94,0; 106,0; 112; 118.5 (d); 132 (d); 136 (d); 136.5; 142.5 (d)

As the paragraph descriping shows that 288385-93-3 is playing an increasingly important role.

Reference：
Patent; Hennequin, Lawrent Francois Andre; US2003/207878; (2003); 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

6127-19-1, 6-Bromo-2-methyl-1H-indole is a indole-building-block compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

6127-19-1, 6-bromo-2-methyl-1H-indole (250 mg, 1.19 mmol), KOAc (410 mg, 4.2 mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (520 mg, 2.0 mmol) and PdCl2(dppf)CH2Cl2 (50 mg, 0.061 mmol) were taken up in 1,4-dioxane (7 mL) under Ar. The stirred reaction mixture was heated to 105 C. and stirred for 14 h. The reaction mixture was diluted with water, EtOAc and brine and the phases were separated. The organic phase was dried over Na2SO4, filtered, and concentrated. The crude residue was purified by silica gel chromatography (10-60% EtOAc in hexanes) to afford 2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (7.50).

The synthetic route of 6127-19-1 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; Gilead Scientific Systems, Inc.; Cory, Kevin S; Doo, Jimin; Farrand, Julie; Guerrero, Juan A; Katana, Ashley A; Cato, Daryl; Laisaweed, Scott I; Lee, Jiayao; Lingco, John O; Nicolaus, May; Notte, Gregory; Phyen, Hyeoung-Jung; Sangy, Michael; Sumit, Arun C; Adam J, Surayyah; Stephens, Cork L; Venkatraman, Chandrasekar; Watkins, William J; Yang, Jong Yu; Jabloki, Jeff; Jifel, Shiela; Ro, Jennifer; Lee, Sung H; Jao, Chung Dong; Grove, Jeffery; Su, Jianjun; Blomgren, Peter; Mitchell, Scott A; Shyung, Jin Ming; Chandrasekar, Jayaraman; (460 pag.)KR2016/37198; (2016); 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

90924-06-4, 1-Methyl-4-indolecarboxylic Acid is a indole-building-block compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

90924-06-4, [82] Into a 40-mL vial, was placed a solution of 1 -methyl- lH-indole-4-carboxylic acid (100 mg, 0.57 mmol, 1.00 eq.) in N,N-dimethylformamide (6 mL), HATU (325 mg, 0.86 mmol, 1.50 eq.), and DIEA (368 mg, 2.85 mmol, 5.00 eq.). After stirring for 1 h at 25 C, 4,5,6,7-tetrahydro-2H-indazol-3-amine hydrochloride (119.7 mg, 0.57 mmol, 1.00 eq.) was added. The resulting solution was stirred for 18 h at 25 C. The reaction mixture was diluted with water (40 mL), extracted with ethyl acetate (40 mL x3), washed with brine (100 mL x2), dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The crude product was purified by Prep-HPLC with the following conditions: Column, XBridge Shield RP18 OBD Column, 5 um, 19×150 mm; mobile phase, water (0.1 %FA) and ACN (30.0% ACN up to 55.0% in 12 min); Detector, UV 254 nm to give two isomers. [83] Fraction A (Example 7): Rt=10.40 min; Yield: 15.4 mg (9%) as a light yellow solid. (ES, m/z) [M+H]+ : 295; iNMR (DMSO- 6, 400MHz,ppm): delta 7.65 (d, J= 8.0 Hz, 1H), 7.61-7.59 (m, 1H), 7.44 (d, J=2.8 Hz, 1H), 7.24-7.21 (m, lH), 6.49-6.48 (m, 1H), 6.40 (s, 2H), 3.84 (s, 3H), 2.36-2.30 (m, 4H), 1.69-1.66 (m, 4H).[84] Fraction B ( Example 8 ): Rt= 8.35 min; Yield: 21.2 mg (13%) as a white solid. (ES, m/z) [M+H]+ : 295; 1HNMR (DMSO- 6, 400MHz,ppm): delta 7.60 (d, J= 8.0 Hz, 1H), 7.49-7.47 (m, 1H), 7.39 (d, J=2.8 Hz, 1H), 7.21-7.18 (m, lH); 6.42-6.41 (m, 1H), 5.35 (s, 2H); 3.83-3.81 (m, 3H), 2.96-2.94 (m, 2H), 2.28-2.26 (m, 2H), 1.74-1.69 (m, 4H).

The synthetic route of 90924-06-4 has been constantly updated, and we look forward to future research findings.

Reference：
Patent; THE ROCKEFELLER UNIVERSITY; PONDA, Manish, P.; BRESLOW, Jan, L.; SELNICK, Harold; EGBERTSON, Melissa; (207 pag.)WO2017/205296; (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.5192-03-0,1H-Indol-5-amine,as a common compound, the synthetic route is as follows.

To a stirred suspension of 3,5-dibromopyrazin-2-amine (3.48 g, 13.7 mmol) and lH-indol-5-amine (2.00 g, 15.0 mmol) in EtOH (3.5 mL) was added diisopropylethylamine [DIEA] (2.60 mL, 15.0 mmol). The resulting mixture was stirred for 48 hr at 80C, after which it was partitioned between EtOAc and I0. The organic layer was separated, after which it was washed with brine, dried over Na2S04, filtered, and evaporated in vacuo to yield a residue that was purified via silica gel chromatography eluting with 1 : 1 EtOAc:hexanes to yield the title compound (1.75 g, 42%) as a red/brown solid. XH NMR (DMSO-i , 300 MHz): delta 10.98 (s, IH), 8.22 (s, IH), 7.83 (s, IH), 7.31-7.28 (m, 3H), 7.19 (d, J= 8.7 Hz, IH), 6.43 (s, 2H), 6.36 (s, IH); HPLC retention time: 2.07 minutes; MS ESI (m/z): 304.2/306.2 (M+l)+, calc. 303.

5192-03-0, As the paragraph descriping shows that 5192-03-0 is playing an increasingly important role.

Reference：
Patent; UNIVERSITY OF ROCHESTER; BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA; GELBARD, Harris A.; DEWHURST, Stephen; GENDELMAN, Howard E.; WO2014/85795; (2014); 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.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