Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | |||||
{[ item.p_purity ]} | {[ item.pr_size ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]} | {[ item.pr_usastock ]} | Inquiry - | {[ item.pr_chinastock ]} | Inquiry - |
* Storage: {[proInfo.prStorage]}
CAS No. : | 933-67-5 | MDL No. : | MFCD00005684 |
Formula : | C9H9N | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | KGWPHCDTOLQQEP-UHFFFAOYSA-N |
M.W : | 131.17 | Pubchem ID : | 70275 |
Synonyms : |
7-Methyl-1H-indole
|
Num. heavy atoms : | 10 |
Num. arom. heavy atoms : | 9 |
Fraction Csp3 : | 0.11 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 0.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 43.26 |
TPSA : | 15.79 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -5.39 cm/s |
Log Po/w (iLOGP) : | 1.72 |
Log Po/w (XLOGP3) : | 2.41 |
Log Po/w (WLOGP) : | 2.48 |
Log Po/w (MLOGP) : | 1.89 |
Log Po/w (SILICOS-IT) : | 3.06 |
Consensus Log Po/w : | 2.31 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 2.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -2.84 |
Solubility : | 0.191 mg/ml ; 0.00145 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.38 |
Solubility : | 0.542 mg/ml ; 0.00413 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -3.63 |
Solubility : | 0.0305 mg/ml ; 0.000232 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.0 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | Stage #1: With sodium cyanoborohydride; acetic acid In N,N-dimethyl-formamide at 20℃; for 2 h; Stage #2: With water; sodium hydroxide In N,N-dimethyl-formamide |
General procedure: 5.1.24. 7-Fluoro-2,3-dihydro-1H-indole (15f) 7-Fluoro-1H-indole (20.0 g, 148 mmol) was dissolved in acetic acid (60 mL) and sodium cyanoborohydride (18.7 g, 296 mmol) was added in portions. The mixture was stirred for 2 h and then poured into 1500 mL of 2 M aqueous NaOH solution. The mixture was extracted with CH2Cl2. The organic layers were combined, washed with brine, dried over MgSO4, and concentrated under reduced pressure to give the title compound (20.0 g, 98percent). 1H NMR (400 MHz, CDCl3) δ 3.08 (2H, t, J = 8.4 Hz), 3.62 (2H, t, J = 8.4 Hz), 6.62-6.66 (1H, m), 6.78-6.83 (1H, m), 6.90 (1H, dd, J = 7.6, 0.4 Hz). |
94% | With sodium cyanoborohydride In acetic acid; ethyl acetate | A. 2,3-Dihydro-7-methylindole. To a stirred solution of 7-methylindole (10.27 g, 78.3 mmol) in glacial acetic acid (50 mL) is added sodium cyanoborohydride (6.33 g, 100.7 mmol) portionwise over a 5 minute period. The reaction solution is allowed to stir for 1 hour. The solution is diluted with water (500 mL) and basified with 50percent sodium hydroxide solution. The basic solution is extracted with three 250 mL portions of diethyl ether. The organic fractions are combined, dried over anhydrous potassium carbonate, filtered and evaporated to give a pink oil. The oil is purified by silica gel column chromatography using 20percent ethyl acetate/hexanes as eluent to give 11.63 g of 2,3-dihydro-7-methylindole as a colorless oil (94percent yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With iodine; oxygen; pyrographite In N,N-dimethyl-formamide at 120℃; for 1.5 h; | General procedure: A 50 mL round bottom flask equipped with a magnetic stirring bar was charged with substituted indole 1 (1.0 mmol, 1.0 equiv), HMTA (2.0 mmol, 0.2803 g, 2.0 equiv), activated carbon (0.1 g) and DMF (2 mL). Then I2 (0.2 mmol, 0.0507g, 20 molpercent) was added and the flask was equipped with a reflux condenser. The reaction mixture was stirred at 120 oC under open air and monitored by TLC. Upon completion of the reaction, the reaction mixture was cooled to room temperature. The resultant mixture was filtered through a pad of celite and the filter cake was washed thoroughly with EtOAc (4 × 6 mL). The filtrate was washed with 0.5 M aqueous HCl (10 mL), saturated NaHCO3 solution (10 mL) and saturated NaCl solution ( 10 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel eluted with hexane and ethyl acetate to give the product. |
88% | With aluminum (III) chloride In N,N-dimethyl-formamide at 120℃; for 1.5 h; | General procedure: A method for synthesizing compound III-1 wherein R1, R2 and R3 are simultaneously hydrogen in the formula III, the method comprising the steps of:(1) Add to a 50 mL round bottom flask1.0mmol indole(In the formula I, R1, R2, and R3 are both hydrogen) and1.0 mmol (0.140 g) of hexamethylenetetramine, then 2 mL of N,N-dimethylformamide (DMF), stirred in a magnetic stirrer to dissolve the solid, followed by the addition of 0.05 mmol (0.012 g) of crystalline trichloride Aluminum, connected to a reflux condenser, heated at 120 ° C, the reaction progress was monitored by TLC, and the reaction was cooled to room temperature after 1 h to prepare a suspension;(2) The suspension prepared in the step (1) is suction filtered with a funnel padded with diatomaceous earth.The filter cake was washed well with ethyl acetate, suction filtered, and the above operation was repeated until the filtrate had no product, and all the filtrates were combined.Dilute with 15 mL of saturated saline solution, disperse and separate the layers, and the aqueous layer was further extracted with ethyl acetate three times.Each time 10 mL, the ethyl acetate layer was combined and washed with 10 mL of 2 mol/L diluted hydrochloric acid.Wash with 10 mL of saturated sodium bicarbonate solution, and finally wash with 10 mL of saturated brine.The washed ethyl acetate layer was dried over anhydrous sodium sulfate, and after drying, the desiccant was filtered off.Then use a rotary evaporator to recover the solvent to concentrate the product, and finally,The residue is subjected to silica gel column chromatography using a mixture of n-hexane-ethyl acetate (V/V = 2:1) as an eluent to obtain a purified product.The mass of the compound III-indole-3-carbaldehyde is 0.137g,The product yield was 94percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With iron(III) chloride; ammonia In water; N,N-dimethyl-formamide at 130℃; for 1.5 h; | General procedure: A 50 mL round-bottomed flask equipped with a magnetic stirringbar was charged with the appropriate indole 1 (0.5 mmol,1.0 equiv), 37percent aq HCHO (0.5 mmol, 0.0406 g, 1.0 equiv), 25percent aqNH3 (1.0 mmol, 0.0681 g, 2.0 equiv), FeCl3 (0.01 mmol, 0.0016 g,2 molpercent), and DMF (2 mL). The flask was fitted with a reflux condenser,and the mixture was stirred at 130 °C under open air.When the reaction was complete (TLC), the mixture was cooledto r.t., diluted with sat. aq NaCl (10 mL) and 0.5 M aq HCl (2 mL),and extracted with EtOAc (3 x 7 mL). The organic layers werecombined, washed with sat. aq NaHCO3 (10 mL) and sat. aq NaCl(10 mL), dried (Na2SO4), and concentrated under reduced pressure.The residue was purified by flash column chromatography(silica gel, hexane–EtOAc). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | Stage #1: 7-methyl-1H-indole; formaldehyd; dimethyl amine With acetic acid In tetrahydrofuran; 1,4-dioxane; water at 0 - 20℃; Inert atmosphere; Stage #2: With sodium hydroxide In tetrahydrofuran; 1,4-dioxane; water | |
With acetic acid | ||
With acetic acid In tetrahydrofuran; 1,4-dioxane; water at 0 - 20℃; |
Stage #1: formaldehyd; dimethyl amine With acetic acid In tetrahydrofuran; 1,4-dioxane; water at 0℃; for 0.0833333h; Schlenk technique; Inert atmosphere; Stage #2: 7-methyl-1H-indole In tetrahydrofuran; 1,4-dioxane; water at 0 - 20℃; Schlenk technique; Inert atmosphere; | ||
Stage #1: formaldehyd; dimethyl amine With acetic acid In water at 0℃; for 0.166667h; Stage #2: 7-methyl-1H-indole In 1,3-dioxane; water at 0 - 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With bismuth(III) chloride In dichloromethane at 20℃; for 6h; | 2. General procedure for the synthesis of 2,3-dihydro-2,3'-bisindoles 2 General procedure: A mixture of N-free indole derivatives 1 (0.5 mmol), BiCl3 (0.5 mmol) in dry CH2Cl2 was stirred for 6 h at rt. Then, the reaction was diluted with ethyl acetate (20 mL), washed with saturated aqueous NaHCO3 solution and brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. After concentrated, the residue was purified by flash column chromatography (silica gel, hexane/EtOAc) to afford the desired products 2. Physical and spectroscopic data follow. |
With hydrogenchloride; benzene | ||
With hydrogenchloride; ethanol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | Stage #1: 7-methyl-1H-indole With sodium hydride In DMF (N,N-dimethyl-formamide) at 20℃; for 0.25h; Stage #2: methyl iodide In DMF (N,N-dimethyl-formamide) at 30℃; for 1h; | II.a; 6.a Preparation 6; Preparation of (1, 7-DIMETHYL-LH-INDOL-2-YLMETHYL) METHYLAMINE; a) 1, 7-DIMETHYL-LH-INDOLE; Scheme II Sodium hydride (1.15 g, 28.7 mmol, 60% in mineral oil) was rinsed with hexanes and then suspended in DMF (20 mL). To this suspension was added 7-methylindole (2.5 g, 19 mmol) portionwise. Gas evolution was allowed to subside between additions. The resulting brown mixture was stirred at room temperature for 15 min and then CH3I (2.71 g, 95.5 mmol) was added in one portion. The exothermic reaction was cooled to 30 °C and stirred for 1 h. Saturated aqueous NH4C1 (10 mL) was added and the mixture was concentrated under reduced pressure. The residue was combined with water (100 mL) and the mixture was then extracted with diethyl ether (3 x 100 mL). The combined organics were washed with brine, dried over NA2SO4, filtered and concentrated under reduced pressure to give the title compound (2.85 g, quantitative) as a red-pink oil which crystallized upon vacuum drying : IH NMR (300 MHz, CDC13) 5 7.43 (d, J= 7. 6 Hz, 1H), 6.97-6. 87 (m, 3H), 6.41 (d, J= 3.1 Hz, 1H), 4.04 (s, 3H), 2.7 (s, 3H). |
99% | With sodium hydroxide In dimethyl sulfoxide at 20℃; | |
97% | Stage #1: 7-methyl-1H-indole With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; Inert atmosphere; Stage #2: methyl iodide In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; Inert atmosphere; |
96% | With sodium hydroxide In dimethyl sulfoxide at 20℃; Inert atmosphere; | |
89% | With sodium hydride In tetrahydrofuran for 4h; | |
81% | With sodium hydride In tetrahydrofuran at 0 - 20℃; | |
73% | Stage #1: 7-methyl-1H-indole With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 0.5h; Stage #2: methyl iodide In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; | |
With sodium hydride 1.) DMF, 0 deg C, 30 min, 2.) DMF, RT, 16 h; Multistep reaction; | ||
Stage #1: 7-methyl-1H-indole With potassium hydroxide In N,N-dimethyl-formamide Stage #2: methyl iodide In N,N-dimethyl-formamide at 20℃; | ||
With potassium <i>tert</i>-butylate In diethyl ether at 0℃; for 24h; | ||
With potassium <i>tert</i>-butylate In diethyl ether at 0℃; for 24h; | ||
With sodium hydride In N,N-dimethyl-formamide Inert atmosphere; | ||
With potassium hydroxide In N,N-dimethyl-formamide at 20℃; for 0.333333h; | ||
Stage #1: 7-methyl-1H-indole With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.5h; Inert atmosphere; Stage #2: methyl iodide In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; | General procedure B: (Substrate 1b-d, 1g-1i) General procedure: To a solution of indole (12.0 mmol) in DMF (60 mL) at 0° C was added NaH (60% dispersion in mineral oil, 14.4 mmol) slowly. The mixture was stirred at this temperature for 30 minutes, then methyl iodide (13.2 mmol) was added drop-wise via syringe. Then the reaction was gradually warmed up to room temperature and stirred for 3 hours. The reaction was quenched with saturated aqueous NH4Cl and diluted with EtOAc (60 mL) and water (60 mL), the organic layer was separated and the aqueous layer was extracted with EtOAc (2×60 mL). The combined organic layers were washed with water (4×60 mL) and brine, dried over anhydrous Na2SO4 and concentrated in vacuo to furnish the desired N-methyl indole as colorless oil that required no further purification. | |
Stage #1: 7-methyl-1H-indole With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.333333h; Stage #2: methyl iodide In N,N-dimethyl-formamide; mineral oil at 20℃; | ||
Stage #1: 7-methyl-1H-indole With sodium hydride In dimethyl sulfoxide; mineral oil at 20℃; for 2h; Inert atmosphere; Stage #2: methyl iodide In dimethyl sulfoxide; mineral oil for 2h; Inert atmosphere; | ||
Stage #1: 7-methyl-1H-indole With sodium hydride In dimethyl sulfoxide; mineral oil at 20℃; for 2h; Inert atmosphere; Stage #2: methyl iodide In dimethyl sulfoxide; mineral oil at 20℃; for 2h; Inert atmosphere; | ||
With sodium hydride In N,N-dimethyl-formamide | ||
With potassium hydroxide In dimethyl sulfoxide at 20℃; | ||
Stage #1: 7-methyl-1H-indole With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 25℃; for 0.5h; Stage #2: methyl iodide In N,N-dimethyl-formamide; mineral oil at 0 - 25℃; | ||
Stage #1: 7-methyl-1H-indole With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; Inert atmosphere; Cooling; Stage #2: methyl iodide In N,N-dimethyl-formamide; mineral oil at 20℃; for 12h; Cooling; Inert atmosphere; | ||
Stage #1: 7-methyl-1H-indole With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.5h; Schlenk technique; Inert atmosphere; Stage #2: methyl iodide In N,N-dimethyl-formamide at 0 - 20℃; Schlenk technique; Inert atmosphere; | ||
With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 4h; | ||
With potassium hydroxide In dimethyl sulfoxide at 20℃; | ||
Stage #1: 7-methyl-1H-indole With sodium hydride In tetrahydrofuran at 20℃; for 1.5h; Inert atmosphere; Stage #2: methyl iodide In tetrahydrofuran at 0 - 20℃; | ||
Stage #1: 7-methyl-1H-indole With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; for 1.25h; Stage #2: methyl iodide In tetrahydrofuran; mineral oil at 0 - 20℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With potassium phosphate; copper(l) iodide; cis-N,N'-dimethyl-1,2-diaminocyclohexane In toluene at 110℃; for 24h; | |
67% | With copper(l) iodide; lithium tert-butoxide In acetonitrile at 20℃; for 24h; Inert atmosphere; Irradiation; | |
62% | With copper(l) iodide; metformin hydrochloride; caesium carbonate In N,N-dimethyl-formamide at 130℃; for 24h; Inert atmosphere; | 4.2.27. 7-Methyl-1-phenyl-1H-indole (3aa). General procedure: 4.2. Experimental procedure for the synthesis of 3: A solution of the indole 1 (1 mmol), aryl halide 2 (1.5 mmol), CuI (0.1 mmol, 10 mol %), metformin hydrochloride (0.2 mmol, 20 mol %), Cs2CO3 (2 mmol, 2 equiv), and DMF (2 mL) was heated to 130 C under N2. The reaction mixture was stirred for the appropriate time (Table 4), and the progress of the reaction was followed by TLC. After completion of the reaction, the mixture was cooled to room temperature, and diluted with EtOAc (10 mL). The solid was removed by filter, and the filtrate was washed with water and brine.The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography to afford the product 3. |
With potassium phosphate; copper(l) iodide; trans-N,N'-dimethylcyclohexane-1,2-diamine In N,N-dimethyl-formamide at 105℃; for 16h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | Stage #1: 7-methyl-1H-indole With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.0833333h; Inert atmosphere; Stage #2: pivaloyl chloride In tetrahydrofuran; hexane at -78 - -20℃; for 0.75h; Inert atmosphere; | 4.2. Synthesis of N-pivaloylindoles. General procedures General procedure: Method A (BuLi as base): To a stirred solution of the starting indole in dry THF (5 mL×mmol) under an argon atmosphere at -78 °C was added a solution of BuLi 1.6 M in hexane (2 equiv). After stirring for 5 min, pivaloyl chloride (1 equiv) was added. The reaction mixture was stirred for 15 min at -78 °C, followed by 15 min at -50 °C and 15 min at -20 °C. When the reaction finished, as judged by TLC, it was poured onto saturated aqueous NH4Cl solution (10 mL/mmol) and it was extracted with AcOEt (3×20 mL). The combined organic layers were dried over Na2SO4 and evaporated to yield the 1-pivaloylindole derivative. |
82% | Stage #1: 7-methyl-1H-indole With potassium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; Inert atmosphere; Stage #2: pivaloyl chloride In tetrahydrofuran; mineral oil for 16h; Inert atmosphere; | |
Stage #1: 7-methyl-1H-indole With sodium hydride In tetrahydrofuran at 20℃; Stage #2: pivaloyl chloride In tetrahydrofuran at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With lithium diisopropyl amide In tetrahydrofuran; hexane at 40 - 45℃; for 40h; | |
93% | With n-butyllithium; diisopropylamine In tetrahydrofuran; hexanes at -78 - 45℃; for 40h; Inert atmosphere; | 4.3. General procedures for the deprotection of N-pivaloylindoles General procedure: Method A: To 1.6 M solution of butyllithium in hexanes (2 equiv) was added dropwise a stirred solution of diisopropylamine (2 equiv) in dry THF (2 mL×mmol) at 0 °C, under an argon atmosphere. Stirring was continued for 10 min at 0 °C, and the solution of LDA thus prepared was added via cannula to a stirred solution of the suitable 1-pivaloyl derivative (1 equiv) in THF (2 mL×mmol), under an argon atmosphere at -78 °C. When addition was complete, the reaction mixture was heated in an oil bath at 40-45 °C for 2 h, cooled and poured onto a saturated aqueous NH4Cl solution (30 mL), which was then extracted with CH2Cl2 (3×15 mL). The combined organic layers were dried over Na2SO4 and evaporated, and the residue was chromatographed on silica gel, eluting with 9:1 EtOAc-petroleum ether. Evaporation of the mobile phase yielded the deprotected indole, which was identical in all respects to the commercially available sample employed as starting material for the protection reaction. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | at 20℃;Ionic liquid; | General procedure: A mixture of xanthen-9-ol 1 (0.040 g, 0.2 mmol) and 2a (0.024 g, 0.2 mmol) was stirred in a tube at room temperature in BmimBF4 (0.5 mL) until the disappearance of the starting 2a (24 h, checked by thin-layer chromatography, TLC). After completing, the reaction mixture was extracted by ethyl ether (3×15 mL), then concentrated and isolated by flash chromatograph to afford the pure product 3a (0.054 g, yield: 92%). |
92% | With betaine dihydrogenphosphate; In octanol; at 50℃; for 3.0h; | In the round bottom flask, ionic liquid [Betaine] [H2PO4] (0.03 mmol), 7-methyl hydrazine (0.3 mmol), and octanol (0.3 mmol) were added in this order, and the mixture was stirred at 50 C, and the whole reaction was carried out. The process was monitored by TLC and reacted for 3 h. Finally, the reaction mixture is extracted with water and ethyl acetate mixture, and after multiple extractions, the organic phase is combined, and the organic phase is steamed under reduced pressure.The crude product was obtained.The crude product was subjected to silica gel column chromatography.Separation gave the pure target product in a yield of 92%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With dmap In dichloromethane at 20℃; for 14h; Schlenk technique; Inert atmosphere; | |
97% | With dmap; triethylamine In 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran at 20℃; for 11h; | |
88% | With dmap; triethylamine In dichloromethane at 20℃; for 8h; | A.1 Step 1 : A mixture of 7-methylindole (5.00 g, 38.11 mmol), di(tert-butyl) carbonate (9.15 g, 0.04 mmol), triethylamine (7.70 g, 0.07 mmol) and 4-dimethylaminopyridine (0.47 g, 0.004 mmol) in dichloromethane was stirred at room temperature for 8 h. The mixture was concentrated under reduced pressure. The residue was purified by flash column chromatography with 0-10% ethyl acetate in petroleum ether to afford tert-butyl 7- methylindole-1-carboxylate (7.80 g, 88%) as a colorless oil. 1H NMR (400 MHz, Chloroform-d) δ 7.68 (d, J = 7.2 Hz, 1H), 7.55 (d, J = 8.0 Hz, 1H), 7.31 - 7.25 (m, 2H), 6.68 (d, J = 7.2 Hz, 1H), 2.84 (s, 3H), 1.78 (s, 9H). |
85% | With dmap In acetonitrile at 20℃; for 0.5h; | |
82% | With cesium fluoride In N,N-dimethyl-formamide at 25 - 30℃; for 1h; | |
67% | Stage #1: 7-methyl-1H-indole With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; Inert atmosphere; Stage #2: di-<i>tert</i>-butyl dicarbonate In tetrahydrofuran; mineral oil at 20℃; for 1h; | 5a Example 5A; 1-tert-Butoxycarbonyl-7-methyl-1H-indole; 22.8 g (174 mmol) of 7-methyl-1H-indole were introduced into 800 ml of absolute tetrahydrofuran under argon at 0° C., 7.30 g (183 mmol) of a 60% strength suspension of sodium hydride in mineral oil were added, and the mixture was stirred at RT for 15 min. 39.8 g (183 mmol) of di-tert-butyl dicarbonate were added, and the mixture was stirred at RT for 1 h. Water was then added and concentrated. The residue was taken up in water and extracted with dichloromethane. The organic phase was dried over magnesium sulfate, filtered and concentrated. The residue was purified by flash chromatography (mobile phase: cyclohexane/ethyl acetate gradient) to result in 27.0 g (67% of theory) of the title compound.1H-NMR (400 MHz, DMSO-d6): δ=2.53 (s, 3H), 1.60 (s, 9H), 6.66 (d, 1H), 7.09 (d, 1H), 7.15 (t, 1H), 7.44 (d, 1H), 7.63 (d, 1H). |
With dmap; triethylamine In dichloromethane at 20℃; for 2h; | 4a Example 4a tert-butyl 7-methyl-i H-indole-1 -carboxylate Di-tert-butyl dicarbonate (3.9 g, 17.87 mmol) was added to a solution of 7-methyl-1H-indole (Aldrich, 2.0 g, 15.25 mmol), triethylamine (2.5 mE, 17.94 mmol), N,Ndimethylpyridin-4-amine (0.187 g, 1.531 mmol) and dichloromethane (25 mE). The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with dichloromethane and was washed with water, brine, dried (magnesium sulfate), filtered and concentrated. The crude product was flash chromatographed (Biotage 100 g HP Snap Cartridge, eluting with heptanes containing a gradient with ethyl acetate, 0% to 6%) to provide the title Example. MS DCI 249.1 (M+NH4). | |
1.7 g | With dmap; triethylamine In acetonitrile at 0 - 20℃; for 16h; | 49 Example 49: To a solution of 7-methyl-1H-indole (1.0 g, 7.62 mmol), DMAP (931 mg, 7.62 mmol,) and Et3N (2.31 g, 22.9 mmol) in MeCN (20 mL) was added Boc2O (1.83 g, 8.38 mmol). The mixture was stirred at 20 °C for 16 h. The mixture was concentrated and the residue was diluted with EtOAc (100 mL). The resulting solution was washed with HCl (20 mL, 1M), NaHCO3 (20 mL, 1M) and brine (20 mL). The organic phase was dried over anhydrous Na2SO4, filtered and concentrated in vacuum to give tert-butyl 7-methyl-1H- indole-1-carboxylate (I-441) (1.7 g) as a yellow oil.1H NMR (400 MHz, DMSO-d6) d 7.52 (d, J = 3.6 Hz, 1H), 7.39 (d, J = 7.4 Hz, 1H), 7.19-7.08 (m, 2H), 6.53 (d, J = 3.6 Hz, 1H), 2.65 (s, 3H), 1.64 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | A. Preparation of 7-methyl-3-piperidin-4-yl-1H-indole This compound was prepared following the procedure described in Example 1 (parts A and B) starting with 1 g (7.6 mmol) of 7-methylindol and 2.9 g (19 mmol) of <strong>[40064-34-4]4-piperidone monohydrate hydrochloride</strong>. After the usual work-up 0.8 g (50% of yield) of the desired product were obtained. ESI/MS m/e=215 [(M+1)+, C14 H18 N2] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With pyridinium chlorochromate In 1,2-dichloro-ethane at 80℃; for 3h; | |
73% | With tert.-butylhydroperoxide; iodine In dimethyl sulfoxide at 80℃; for 24h; | |
69% | With oxygen; Rose Bengal lactone In water; N,N-dimethyl-formamide for 18h; Inert atmosphere; Irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | F. 7-Methyl-1 - 2-morpholin-4-yl-ethyl)-1 H-indoleTo a solution of 7-methylindole (1 .01 g, 7.70 mmol) in N,N-dimethylacetamide at r.t. is added sodium hydride (217 mg, 10.73 mmol). The resulting mixture is stirred for 30 minutes at r.t. then <strong>[89583-07-3]2-(4-morpholine)ethyl bromide</strong> (1 .64 g, 8.45 mmol) is added and the resulting mixture is stirred at r.t. overnight. The mixture is diluted with water (100 ml_) and ethyl acetate (50 ml_). The organic is separated and the aqueous phase is extracted again with ethyl acetate (50 mL). The organic phase is washed with brine then separated and dried over MgSO . The organic phase is concentrated in vacuo and the crude residue is flash chromatographed over S1O2 using 50% EtOAc /heptane as the eluent to afford the title compound (1 .60 g, 85%) as an orange oil. 1 H NMR (300 MHz, CDCI3) delta 7.45 (d, 1 H), 7.04 (d, 1 H), 7.00-6.90 (m, 2H), 6.45 (d, H), 4.44 (t, 2H), 3.69 (m, 4H), 2.72-2.67 (m, 5H), 2.45 (m, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With pyridine In tetrahydrofuran at 0 - 20℃; | 5.A A. 2,2,2-Trichloro-1 - 7-methyl-1 H-indol-3-yl)-ethanoneTo a solution of 7-methylindole (10g, 76.3 mmol) in THF (200 mL) at 0 °C is added pyridine (8 mL, 99.2 mmol) followed by dropwise addition of trichloroacetyl chloride (1 1 mL, 99.2 mmol). The reaction mixture is allowed to warm to r.t. and stir overnight. The reaction mixture is poured into EtOAc and washed with 1 N HCI (2X). The organic layers are washed with brine, dried over MgSO4, filtered, and concentrated in vacuo to give the crude product. Purification by flash chromatography on S1O2 eluting with 20% ethyl acetate/heptane gives the title compound (19 g, 90% yield).1 H NMR (300 MHz, DMSO-c/6) δ 12.6 (bs, 1 H), 8.5 (s, 1 H), 8.0 (d, 1 H), 7.2 (m, 1 H), 7.15 (m, 1 H), 3.2 (s, 3H);MS m/z: [M+H]+=276, 278. |
1.05 g | With pyridine In dichloromethane at 0 - 20℃; | 49 7-Methyl-1-(2-naphthylmethyl)-N-[(3R,4R,5S,6R)-2,4,5-trihydroxy-3,6- bis(hydroxymethyl)tetrahydropyran-3-yl]indole-3-carboxamide 7-Methyl-1H-indole (1.0 g, 7.6 mmol) was dissolved in DCM (20 mL) and pyridine (1.85 mL, 22.9 mmol) was added. The solution was cooled to ~ 0 ^C, and a solution of trichloroacetyl chloride (1.28 mL, 11.4 mmol) in DCM (5 mL) was added over the course of about 30 min. The cooling bath was removed and the reaction mixture was stirred at rt overnight. All the volatiles are removed under reduced pressure. The mixture was then stirred with ethanol-water (1:1, 15 mL) for 10 min, and the product was filtered off and dried. Further purification by silica gel flash chromatography eluting with 0-100% ethyl acetate gradient in hexanes to give 2,2,2-trichloro-1-(7-methyl-1H-indol-3-yl)ethanone (1.05 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With dichloro bis(acetonitrile) palladium(II); norbornene; water; potassium carbonate In N,N-dimethyl acetamide at 70℃; for 18h; Inert atmosphere; regioselective reaction; | |
68% | With dichloro bis(acetonitrile) palladium(II); potassium carbonate; norbornene In N,N-dimethyl acetamide; water at 70℃; for 18h; Schlenk technique; Inert atmosphere; regioselective reaction; | Procedure 1a (Tables 1 and 2) General procedure: A 50-mL Schlenk flask equipped with a magnetic stirring bar and a rubber septum was charged with 1H-indole substrate 1 (1.00 mmol), norbornene (188 mg, 2.00 mmol), the base [K2CO3 (276 mg, 2.00mmol), KHCO3 (300 mg, 3.00 mmol), or K2HPO4 (522 mg, 3.00mmol) as indicated], and PdCl2(MeCN)2 (25.9 mg, 0.100 mmol). A 0.5 M solution of H2O in DMA (5 mL) was added. The alkyl bromide 2 (2.00 mmol) was then added from a syringe, and the resulting mixture was degassed by three freeze-pump-thaw cycles with liquid nitrogen under high vacuum. The flask was then placed in an oil bath preheated to 70 °C or 90 °C, as indicated, and the mixture was stirred vigorously under balloon pressure of argon. Upon completion of the reaction (TLC), the mixture was cooled to r.t., diluted with Et2O (30 mL), and filtered. The filtrate was concentrated in arotary evaporator (60 °C water bath, 8-10 mbar) to remove the Et2O and most of the DMA. The residue was purified directly by flash column chromatography [silica gel (dry loading)] to give the alkylation product 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With nickel(II) perchlorate hexahydrate; 2,2-bis<2-<4(R),5(R)-diphenyl-1,3-oxazolinyl>>propane In toluene at 60℃; for 48h; Schlenk technique; Inert atmosphere; enantioselective reaction; | |
76% | Stage #1: 7-methyl-1H-indole With nickel(II) perchlorate hexahydrate; C53H42N2O2 In toluene at 20℃; for 1h; Inert atmosphere; Schlenk technique; Sealed tube; Stage #2: (E)-(3,3,3-trifluoro-1-nitroprop-1-en-2-yl)benzene In toluene at 100℃; for 36h; Inert atmosphere; Schlenk technique; Sealed tube; enantioselective reaction; | 3.2 Asymmetric synthesis of indole derivatives containing a trifluoromethylated all-carbon quaternary center though 1,4-addition reactions General procedure: In an argon-filled glovebox, Ni(ClO4)2.6H2O (4.0 mg, 0.011 mmol, 11 mol%), L1 (7.4 mg, 0.01 mmol, 10 mol% ), and indole or substituted indole (0.15 mmol, 1.5 equiv.) were added to a Schlenk tube equipped with a magnetic stir bar. After the reaction tube was sealed with a rubber stopper, it was removed from the glove box and the newly distilled anhydrous toluene (1.0 mL) was added to the tube with a syringe. The reaction was stirred at room temperature for 1 hour and then the disubstituted nitroalkene (0.1 mmol, 1.0 equiv.) was added to the tube carefully with a microinjector. Subsequently, the Schlenk tube was placed into an oil bath which was pre-heated to 85 °C or 100 °C. In order to reduce the volatilization of the toluene, the upper part of the Schlenk tube was cooled by air flow from an electric fan. When the reaction was complete, the solvent was concentrated in vacuo and the residue was subjected to flash silica gel column chromatography (PE/EA = 10:1- 5:1) to afford the product. The enantiomeric excesses were determined by HPLC analysis using chiral stationary phases. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With [Cp2Hf2(H2O)6(μ2-OH)2(OSO2C4F9)4·4H2O·2THF] In acetonitrile at 20℃; for 2.5h; | |
86% | With C48H30F10O7S2Sb2 In acetonitrile at 20℃; | General procedure for the Michael addition reaction of indoles to α, β-unsaturated carbonyl compounds and trans-β-Nitrostyrene General procedure: A mixture of α, β-unsaturated carbonyl compound/trans-β-Nitrostyrene (1.0mmol), indoles (1mmol) and 2 or 3 (0.05mmol) in acetonitrile (1mL) was stirred at room temperature for the appropriate reaction time and monitored by TLC. Then the solvents of the resulted mixture were removed by evaporation in vacuum, CH2Cl2 (10mL×3) was added to the reaction mixture and the catalyst was filtered for the next cycle of reaction. To the filtrate, after evaporation of the solvent a Pinkish solid mixture was obtained. The residue was performed by a short column chromatography eluted with ethyl acetate/petroleum ether (80/20). |
45% | With C4H3O5(3-)*C12H8N5(1-)*4.5H2O*2Co(2+) In dichloromethane at 35℃; for 24h; Inert atmosphere; |
With (R)-(4-hydroxy-4-oxidodinaphtho[2,1-d:1',2'-f][1,3,2]di-oxaphosphepine-2,6-diyl)bis(tri-p-tolylphosphonium)tetrakis[3,5-bis(trifluoromethyl)phenyl]borate In dichloromethane; benzene at -30℃; for 58h; Molecular sieve; Sealed tube; Inert atmosphere; Optical yield = 90 percent ee; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With trifluorormethanesulfonic acid; sodium sulfate In neat (no solvent) at 115℃; for 12h; Sealed tube; Inert atmosphere; | 3,3'-(1-Cyclopropyl-2,2,2-trifluoroethane-1,1-diyl)bis(7-methyl-1H-indole)(3k) General procedure: Trifluoromethyl ketone (0.3mmol),trifluoromethanesulfonicacid (9mg, 0.06mmol) were added to a dry sealed tube charged with indole(0.9mmol) and sodium sulphate anhydrous (12.8mg, 0.09mmol) under argon. Thereaction mixture was stirred at 115°C for 12h. After the reaction was completed, the mixture was purifiedby column chromatography on silica gel with hexanes/ethyl acetate as eluent.The desired product was obtained as white or pale yellow solid. Isolated yield: 82%. White solid. M.P.: 116-120oC.1H NMR (400 MHz, CDCl3) δ 8.10 (s, 2 H), 7.44 (d, J= 2.0 Hz, 2 H), 6.82 (d, J = 6.8 Hz, 2 H), 6.68-6.60 (m, 4 H), 2.46(s, 6 H), 2.02-1.95 (m, 1 H), 0.59-0.54 (m, 2 H), 0.29-0.25 (m, 2 H); 19FNMR (375 MHz, CDCl3) δ -69.53 (s, 3 F); 13C NMR(100.7 MHz, CDCl3) δ 135.6, 128.6 (q, J = 284.8 Hz), 126.7,124.3 (q, J = 2.2 Hz), 122.1, 119.8, 119.4, 119.3, 50.4 (q, J = 26.0Hz), 16.5, 15.4 (q, J = 2.2 Hz), 2.2 ppm. IR (KBr): ν = 3415, 3050,3012, 2959, 2922, 2855, 1615, 1541, 1495, 1457, 1431, 1409, 1380, 1345, 1319,1251, 1185, 1147, 1123, 1098, 1068, 1028, 1017, 994, 960, 924, 883, 844, 817,782, 750, 723, 581, 516, 483, 458 cm-1. MS (EI): m/z (%) 382(M , 100), 354, 313, 251,157, 144, 57. HRMS: Calculated for C23H21F3N2: 382.1657; Found: 382.1652 |
82% | With trifluorormethanesulfonic acid; sodium sulfate In neat (no solvent) at 115℃; for 12h; Sealed tube; Inert atmosphere; Green chemistry; | Representative procedure ofthe reaction of indole with 1 General procedure: Trifluoromethylketone (0.3mmol),trifluoromethanesulfonic acid (9mg, 0.06mmol) were added to a dry sealedtube charged with indole (0.9mmol) and sodium sulphate anhydrous(12.8mg, 0.09mmol) under argon. The reaction mixture was stirred at 115°C for12h. After the reaction was completed, the mixture was purifiedby column chromatography on silica gel with hexanes/ethyl acetate as eluent.The desired product was obtained as white or pale yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With iodine; oxygen; palladium diacetate; caesium carbonate In 1-methyl-pyrrolidin-2-one at 45℃; for 12h; Schlenk technique; Sealed tube; | Representative procedure for the synthesis of 3-acylindoles (3) General procedure: A 10 mL oven-dried Schlenk tube was charged with phenylglyoxylic acid 1a (49.5mg, 0.33mmol), indole 2a (35.1mg, 0.3mmol), I2 (164.5mg, 0.65mmol), Pd(OAc)2 (10mol%, 6.7mg, 0.03mmol), Cs2CO3 (292mg, 0.9mmol). The tube was evacuated and filled with O2 (this procedure was repeated three times). Then NMP (1.5mL) were added with a syringe under a counter flow of O2. The tube was sealed with a screw cap. The reaction was stirred at 45°C for 12h, and was then allowed to cool to ambient temperature. The mixture was added 20mL EtOAc, and filtered, washed with water. The organic layers were dried over Na2SO4 and filtered. Solvents were evaporated under reduced pressure. The residue was purified by flash column chromatography with hexane/ethyl acetate to give the corresponding product 3. |
67% | With rose bengal In ethanol at 20℃; for 10h; Molecular sieve; Irradiation; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With C40H32N4O7Ti2(2+)*2C8F17O3S(1-) In tetrahydrofuran at 20℃; for 0.416667h; | 1.2 General Procedure for Synthesis of bis(indolyl) methanes: General procedure: A mixture of carbonyl compound (1 mmol), indole (0.234 g, 2 mmol) and 1 (17.7 mg, 1 mmol%) in THF (0.5 mL) was stirred at room temperature for the appropriate reaction time under the TLC analysis until indole was consumed completely. Then the solvents of the resulted mixture were removed by evaporation in vacuum, and the residue was dissolved in diethyl ether (30 mL) followed by filtration. After the catalyst was washed three times with diethyl ether (10 × 3 mL), and the catalyst was used for catalyzing the next cycle of reaction. To the filtrate, after evaporation of the solvent a dark grayish solid mixture was obtained. Purification of the product was performed by a short column chromatography eluted with ethyl acetate/petroleum ether (1:3) to give the desired product. |
88% | With boron trifluoride diethyl ether complex In diethyl ether at 20℃; for 2h; | 1.2 Typical procedure for the synthesis of bis(indolyl)methanes General procedure: BF3·Et2O (21.3 mg, 0.15 mmol) was added to a mixture of indole 1 (234.4 mg, 2 mmol) and benzaldehyde 2a (106.1 mg, 1 mmol) in diethyl ether (2 mL). The reaction mixture was stirred at room temperature for 2 h in the atmosphere and monitored by TLC. After completion of the reaction, the volatile components were removed using a vacuum rotary evaporator. The resulting residue was purified by column chromatography on silica gel column using EtOAc/petroleum ether solution (1:15-1:8, v/v) as eluent to afford a pink solid bis(indolyl)phenylmethane 3a |
88% | With triphenyl bismuth(V) bisperfluorooctanesulfonate In tetrahydrofuran at 20℃; for 2h; |
88% | With triphenylbismuth(V) bis(perfluorooctanesulfonate) In tetrahydrofuran at 20℃; for 2h; | 19 Preparation Example 17 To a 50 ml round bottom flask, add benzaldehyde 0.5 mmol in sequence.7-methyl hydrazine 1.0 mmol, catalyst Ph3BiX2 (X=OSO2C8F17) 0.025 mmol, THF 0.5 ml, react at room temperature, the reaction progress was detected by TLC, after 2 h, the starting material was completely reacted, the solvent was removed, diluted with diethyl ether, filtered, and recovered. catalyst.The filtrate is spun dry to obtain a crude product, which is separated by column chromatography.3,3'-bis(7-methylindenyl)phenylmethane in a yield of 88%. |
79% | Stage #1: benzaldehyde With ferric(III) chloride; 2,2-dimethyl-1,3-dioxane-4,6-dione; ethanol at 80℃; for 7h; Green chemistry; Stage #2: 7-methyl-indole In ethanol at 80℃; for 5h; Green chemistry; | General procedure for the synthesis of bis(indolyl)methanes 3 General procedure: Aromatic aldehydes 1 (0.2 mmol), Meldrum’s acid (0.2 mmol) and Anhydrous FeCl3 (0.02 mmol) were dissolved in ethanol (2 mL). Subsequently, the mixture was stirred in a preheated oil bath at 80 °C for 7 h. Indoles 2 (0.4 mmol) was then added to the reaction system quickly and was stirred at 80 °C for another 5 h. Upon completion, the mixture was cooled to room temperature, diluted with CH2Cl2 (310 mL), and washed with brine. The organic layers were combined, dried over Na2SO4, filtered, and then evaporated in vacuum. The residue was purified by flash column chromatography on silica gel (200-300 mesh), with ethyl acetate and petroleum ether (1:5, v:v) as the elution solvent to give the desired products 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione In 1,4-dioxane at 10℃; | General Procedure for the 3-bromination ofIndoles General procedure: DBDMH (157 mg, 0.55 mmol) was added in five potion to a solution ofindoles (1.0 mmol) in dioxane at 10 °C over two minutes with stir, and the resulting solution was stirred for 5to 10 minutes. TLC indicate that the reaction is completed. The reactionsolution was poured into the saturated NaHCO3 solution (10 mL), themixtures was extracted by ethyl acetate (15 mL*2). The organic phase was dried over Na2SO4,filtered, concentrated under reduced pressure. The residue was then purified byflash chromatography on 200~300 mesh silica gel to provide the correspondingproduct 2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With 1,3-dichloro-5,5-dimethylhydantoin In 1,4-dioxane at 25℃; for 3h; | General Procedure for the 3-chlorination of Indoles General procedure: DCDMH(108mg, 0.55mmol) was added to a solution of indoles (1.0 mmol) in 1.4-dioxaneat room temperature, and the resulting solution was stirred up to transformcompletely. The reaction solution was poured into the saturated NaHCO3solution (10 mL), the mixtures was extracted by ethyl acetate (15 ml*2). The organic phase was dried over Na2SO4,filtered, concentrated under reduced pressure. The residue was then purified byflash chromatography on 200~300 mesh silica gel to provide the correspondingproduct 4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | Potassium tert-butoxide (410 mg, 3.6 mmol) is added to a mixture of 7-methyl-1H-indole (470 mg, 3.6 mmol) in DMSO (20 ml) with ice cooling. Stirring is continued for 10 minutes before <strong>[3512-17-2]2,4,6-trifluoropyridine</strong> E (350 mul, 3.6 mmol) is added dropwise. The mixture is warmed to RT and stirred for 2 h. The mixture is diluted with DCM and extracted with water. The combined organic layers are dried over MgSO4 and concentrated in vacuo. The product is purified by RP HPLC. Yield: 350 mg (40%). HPLC-MS: M+H=245; tR=1.03 min (Method-2). | |
40% | Potassium tert-butoxide (410 mg, 3.6 mmol) is added to a mixture of 7-methyl-lH-indole (470 mg, 3.6 mmol) in DMSO (20 ml) with ice cooling. Stirring is continued for 10 minutes before <strong>[3512-17-2]2,4,6-trifluoropyridine</strong> E (350 mu, 3.6 mmol) is added dropwise. The mixture is warmed to RT and stirred for 2 h. The mixture is diluted with DCM and extracted with water. The combined organic layers are dried over MgSC^ and concentrated in vacuo. The product is purified by RP HPLC. Yield: 350 mg (40%). HPLC-MS: M+H=245; tR=l .03 min (Method_2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With ortho-nitrobenzoic acid; palladium diacetate; silver(I) oxide In N,N-dimethyl-formamide at 20℃; for 15h; | |
64% | With norborn-2-ene; bis(acetonitrile)palladium(II) chloride; potassium carbonate In N,N-dimethyl acetamide; water monomer at 70℃; regioselective reaction; | 2. General procedure for 2-arylation of free (N-H) indoles General procedure: A high pressure tube equipped with a magnetic stirring bar was charged with indole substrate (0.2mmol, 1 equiv.), norbornene (0.4mmol, 2 equiv.), the base (0.4mmol, 2 equiv. K2CO3 or 2 equiv. KHCO3, as indicated),, and PdCl2(MeCN)2 (0.02mmol, 10 mol %). A solution of water (0.5 M) in DMA (1mL) was added via syringe, and then the aryl iodide (0.4mmol, 2 equiv.) was added via syringe. The reaction mixture was then placed in a preheated oil bath at 70 °C (or 90 °C, as indicated). Vigorous stirring was applied. The reaction was monitored by TLC. Upon completion, the reaction mixture was cooled to room temperature, diluted with EtOAc, and filtered. The filtrate was extracted with H2O (3 times) and brine, the organic phase was concentrated in vacuum to remove the solvent. The residue was directly submitted to flash column chromatography to afford the 2-arylindole product. The spectral data of the products were in accordance with those reported in the literature1. |
With norborn-2-ene; bis(acetonitrile)palladium(II) chloride; potassium carbonate In N,N-dimethyl acetamide; water monomer at 70℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With ruthenium(III) chloride trihydrate; sodium nitrite; In N,N-dimethyl-formamide; at 40℃; for 11h;Green chemistry; | General procedure: RuCl3*3H2O (0.075 mmol) was added to a solution of indole (0.50 mmol), alkyl bromide (0.7 mmol), and NaNO2 (1.0 mmol) in DMF (1mL) under atmosphere and the mixture was stirred at 40 C for 8-26 h (monitored by thin-layer chromatography, TLC). The reaction mixture was concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (eluent: EtOA/PE 1:4) to yield the corresponding product. |
With ruthenium(III) chloride trihydrate; sodium nitrite; In N,N-dimethyl-formamide; at 40℃; | General procedure: To a solution of indole (0.50mmol), alkyl bromide (0.7mmol) and NaNO2 (1.0mmol) in DMF (1mL) was added RuCl3·3H2O (0.075mmol) under atmosphere and the mixture was stirred at 40C for 8-26h (monitored by TLC). The reaction mixture was concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (eluant: EtOAc/PE=1:4) to yield the corresponding product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With aluminium(III) chloride hexahydrate In dichloromethane at 20℃; for 3h; Sealed tube; | 3.3. General Procedure for the Friedel-Crafts Alkylation General procedure: Celastrol (2a, 0.222 mmol, 100 mg) and indole (3a, 0.266 mmol, 31 mg) were dissolved in dichloromethane (DCM, 2 mL) in a 10 mL closed tube. After intensive stirring at room temperature,the metal catalyst AlCl3.6H2O (5 mol %, 2.7 mg) was added to the solution and the reaction mixturewas stirred for 3 h. When the reaction was finished, pure water (20 mL) was added to stop the reaction and subsequently the aqueous phase was separated and extracted with ethyl acetate (20 mL) three times. The organic layers were combined and dried with anhydrous sodium sulfate. The solvent was removed in vacuo, giving a crude mixture which was purified by flash chromatography on silica column (hexane/ethyl acetate/AcOH = 4:1:0.005) to give the pure products 3a-3q, 1a2b, 1a2c.NMR spectra for all compounds can be found in Supplementary Materials. |
With scandium tris(trifluoromethanesulfonate) In dichloromethane at 20℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | With tris(2,2-bipyridine)ruthenium(II) hexafluorophosphate; chloropyridinecobaloxime(III) In acetonitrile at 20℃; Irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | Stage #1: 7-methyl-1H-indole With gallium tris(dodecyl sulfate) In water for 0.166667h; Green chemistry; Stage #2: propynoic acid ethyl ester In water at 105℃; for 18h; Green chemistry; regioselective reaction; | General synthesis of ethyl 3,3-di(1H-indol-3-yl)propanoate (3a) General procedure: Gallium tris(dodecylsulfate) (0.05 mmol), indole (1 mmol) and water (25 mL) was added into a 100 mL screw capped tube. After vigorous stirring for 10 minutes, ethyl propiolate (1.2 mmol) was added, followed by screwing and heating to 70°C for 18 hours. After completion of reaction (as monitored by TLC), a little amount of sodium chloride was introduced, then the reaction mixture was extracted with ethyl acetate. Dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to leave the crude product which was purified by chromatography over silica gel. |
96% | With gallium(III) dodecyl sulfate In water at 110℃; for 18h; | General procedure for the reaction of indole derivatives and propiolates General procedure: To a mixture of Ga(DS)3 (0.05 mmol), indole derivative (1.0 mmol) and propiolate (1.0 mmol) in 10 mLwater. The mixture was stirred at desired temperature for an appropriate time. After cooling to rt, brinewas added and the product was extracted by EtOAc. The organic layer was separated, dried over anhydrous Na2SO4 and evaporated. The residue was purified by column chromatography, usingacetone/petroleum ether as the eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With rhodium(II) pivalate In fluorobenzene at 20℃; Inert atmosphere; regioselective reaction; | |
91% | With rhodium(II) pivalate In fluorobenzene at 20℃; Inert atmosphere; | General procedure for synthesis of 3-naphthalenyl indoles 3a-r General procedure: To a solution of 1-diazonaphthalene-2-(1H)-ones (1a-d) (1 mmol) and indoles (2a-k) (1.1 mmol) in PhF (5 mL) was added Rh2(OPiv)4 (2 mol%). The reaction was stirred under nitrogen atmosphere for 4-6 h. Then, the solvent was evaporated in rotary evaporator under reduced pressure. The residue thus obtained was purified by flash column chromatography on silica gel to isolate the product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | General procedure: A heterogeneous mixture of <strong>[521-73-3]isoquinoline-1,3,4-trione</strong>(17.5 mg, 0.1 mmol), indole (14.0 mg, 0.12 mmol) and alginic acid (1.76 mg,0.01 mmol, purchased from Sigma Aldrich) in H2O (0.2 mL) was stirred for 24 h(monitored by TLC). Afterwards, the reaction mixture was concentrated under reduced pressure to leave the crude residue which was purified by column chromatography over silica-gel using ethyl acetate/hexane as a mixture of solvent to give the pure compound 3aa in75% yield (21.9 mg) as a white solid.4-Hydroxy-4-(1H-indol-3-yl)isoquinoline-1,3(2H,4H)-dione (3aa): yield 75%; mp:188-190 C; Rf = 0.25 (EtOAc/hexane = 1:3); 1H NMR (400 MHz, acetone-d6) d10.24 (br s, 1H, NH), 10.10 (br s, 1H, NH), 8.14 (d, J = 7.8 Hz, 1H), 7.89 (d,J = 7.8 Hz, 1H), 7.76-7.79 (m, 2H), 7.59-7.63 (m, 1H), 7.36 (d, J = 8.2 Hz, 1H),7.06-7.10 (m, 1H), 6.96-7.00 (m, 1H), 6.65-6.66 (m, 1H), 5.66 (br s, 1H, OH); 13CNMR (100 MHz, acetone-d6) d 175.0 (CO), 164.7 (CO), 144.3, 138.0, 134.7,129.2, 128.2, 127.9, 125.8, 125.8, 124.8, 122.6, 122.4, 121.7, 120.1, 112.4, 74.7(C-4, quaternary); HRMS (ESI) m/z calcd For C17H12N2O3 [M+Na]+: 315.0897.Found 315.0953. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With <i>L</i>-proline In ethanol at 25℃; for 38h; Green chemistry; | 4.1. General procedure for the L-proline-catalyzed multicomponent reaction General procedure: The aldehyde (or 2,2,2-trifluoroacetophenone) (1.0 mmol),malononitrile (1.0 mmol), indole (or pyrrole) (1.0 mmol), L-proline(10 mol %) and ethanol (1.0 mL) were added sequentially into a round-bottom flask to form a clear yellow solution. The resultant mixture was stirred at rt for a specific time. After completion of the reaction, the solvent was removed under reduced pressure, and the residue was purified by silica gel flash column chromatography with petroleum ether/ethyl acetate as eluent to give the desired product. |
93% | With <i>L</i>-proline In ethanol at 20℃; for 38h; | 3 3, Preparation of 3-substituted indole derivatives General procedure: Under optimal conditions, L-proline catalytic effect on compound 1, compound 2, and compound 3 (malononitrile). The results are shown in Table 3. a. Reaction conditions: aldehyde (1.0mmol), indole (1.0mmol), malononitrile (1.0mmol), L-proline (10mol%), ethanol (1.0mL) at room temperature. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With <i>L</i>-proline In ethanol at 25℃; for 42h; Green chemistry; | 4.1. General procedure for the L-proline-catalyzed multicomponent reaction General procedure: The aldehyde (or 2,2,2-trifluoroacetophenone) (1.0 mmol),malononitrile (1.0 mmol), indole (or pyrrole) (1.0 mmol), L-proline(10 mol %) and ethanol (1.0 mL) were added sequentially into a round-bottom flask to form a clear yellow solution. The resultant mixture was stirred at rt for a specific time. After completion of the reaction, the solvent was removed under reduced pressure, and the residue was purified by silica gel flash column chromatography with petroleum ether/ethyl acetate as eluent to give the desired product. |
95% | With <i>L</i>-proline In ethanol at 20℃; for 42h; | 3 3, Preparation of 3-substituted indole derivatives General procedure: Under optimal conditions, L-proline catalytic effect on compound 1, compound 2, and compound 3 (malononitrile). The results are shown in Table 3. a. Reaction conditions: aldehyde (1.0mmol), indole (1.0mmol), malononitrile (1.0mmol), L-proline (10mol%), ethanol (1.0mL) at room temperature. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With aminosulfonic acid In neat (no solvent) at 90℃; for 1h; | 3.2. General Procedure for the Reaction of Indoles with Nitrochalcones to give Products 3a-3v General procedure: The mixture of nitrochalcone (2.0 mmol), indole (2.2 mmol), and sulfamic acid (1 mmol, 0.5 eq.) was heated at 90 °C until the complete consumption of starting materials, which was monitored by TLC. Then, the reaction mixture was allowed to cool to room temperature, diluted with ethyl acetate (20 mL) and washed with water, followed by brine. The organic layer was separated, dried over anhydrous MgSO4, and concentrated in vacuum to obtain the crude product. The residue was purified by flash column chromatography (petroleum ether/ethyl acetate) to obtain the desired products 3a-3v. (The 1H-, 13C-NMR spectra of the compounds (3a-3v) was showed in Supplementary). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With dimethyl sulfoxide; phosphonic acid diethyl ester; copper(l) chloride In toluene at 110℃; for 12h; Inert atmosphere; Sealed tube; | |
88% | With Dichlorophenylphosphine In 1,4-dioxane at 60 - 70℃; for 0.5h; Schlenk technique; | 3.2 General procedure for trifluoromethylthiolation of electron-rich aromatic by CF3SO2Na in the presence of PhPCl2 General procedure: To a flame-dried Schlenk tube was added electron-rich aromatic (0.5mmol), CF3SO2Na (118mg, 0.7mmol) dry 1,4-dioxane or CH3CN (1mL). The mixture was heated to 60°C by a preheated oil bath. PhPCl2 (125mg, 0.7 mmoL) was added. The reaction mixture was stirred at 70°C for the indicated time. Then the reaction mixture was cooled to room temperature. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to afford the pure product. |
87% | With N-chlorophthalimide; triphenylphosphine; eosin y In acetonitrile at 20℃; for 6h; Inert atmosphere; Schlenk technique; Irradiation; | 13 Example 13: Preparation of 7-methyl-3-trifluoromethylthioindole 10 mL of Schlenk tube was added Eosin Y (0.01 mmol), sodium trifluoromethanesulfinate (0.3 mmol), triphenylphosphine(0.6 mmol), N-chlorophthalimide (0.3 mmol), evacuated and washed into dry nitrogen (this procedure was repeated three times)7-methylindole (0.2 mmol) was dissolved in the ultra-dry solvent acetonitrile and the resulting solution was passed through a syringe into a Schlenk tube. Room temperature, The reaction was allowed to stand under a white LED lamp and stirred for 6 hours. After completion of the reaction, the solvent was evaporated and the residue was passed through the residuePurification by silica gel column chromatography gave 40 mg of product, yield 87%. |
73% | With hydrogenchloride; 1-hexyl-3-methyl-1-imidazolium bromide In water at 60℃; for 5h; Ionic liquid; chemoselective reaction; | General procedures for the trifluoromethylthiolation of indole and its derivatives General procedure: A mixture of indole (or its derivatives) 1 0.25 mmol, CF3SO2Na 2 0.30 mmol and [Hmim]Br 0.5 mL was charged in an oven-dried reaction vessel, and then concentrated HCl (37 wt.% aqueous solution, 0.5 mmol) was added followed by heating the mixture at 60 oC and stirring for 5 h. Upon completion, the reaction mixture was diluted with MTBE (4.0 mL), filtered through a bed of silica gel layered over Celite. The volatiles were removed in vacuo to afford the crude product. Further column chromatography on silica gel (EtOAc/petroleum ether) was needed to afford the pure desired products 3. |
72% | With phosphorus trichloride In acetonitrile at 60℃; for 0.5h; Schlenk technique; Inert atmosphere; | |
72% | With phosphorus trichloride In acetonitrile at 60℃; for 0.5h; Schlenk technique; | 12 Example 12 An indole derivative (0.5 mmol) and sodium trifluoromethyl sulfinate (0.6 mmol) to a 15 mL schlenck tube.And acetonitrile (2.0 mL), then phosphorus trichloride (0.6 mmol) was dissolved in acetonitrile (1.0 mL) at 60 ° C, and added dropwise with a syringe.In the schlenck tube, after 0.5 h, the plate was detected to be completely reacted, and petroleum ether: ethyl acetate = 10:1 was used as the mobile phase. Yellow solid, yield 72%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With copper(II) bis(trifluoromethanesulfonate) In acetonitrile at 25℃; for 2h; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With oxygen In tetrahydrofuran at 25℃; for 7h; Irradiation; | |
93% | With copper(II) choride dihydrate; oxygen In ethanol at 20℃; for 24h; Irradiation; | 15 Example 15: The CuCl2·2H2O catalytic system catalyzes the reaction of 7-methylindole and ammonium thiocyanate. Add 7-methylindole (0.2 mmol), NH4SCN (0.6 mmol), CuCl2·2H2O (20 mol%) and ethanol (2mL) to a dry reaction tube with a magnetic stir bar, place the reaction tube in In the O2 atmosphere,Under the irradiation of a 45 W incandescent lamp, the reaction was stirred at room temperature for 24 h. After the reaction is completed, after the solvent is rotary evaporated,5 mL of saturated brine was added, followed by extraction with 3×5 mL of ethyl acetate, and the organic phases were combined,The organic phase is then dried over anhydrous magnesium sulfate and filtered,After the filtrate was concentrated by rotary evaporation, it was separated by silica gel column chromatography to obtain the target product (yield 93%). |
90% | With TiO2/MoS2 In acetonitrile at 20℃; for 16h; Irradiation; | Typical procedure for the thiocyanation of indole and reuse of the catalyst General procedure: To a solution of indole 1 (0.2 mmol) and ammonium thiocyanate (0.6 mmol) in CH3CN (2 mL) was added TiO2/MoS2 (10: 1, molar ratio, 20 mg). The reaction mixture was stirred under a 14 W CFL irradiation at room temperature for a certain time. After reaction (monitored by TLC), ethyl acetate was added, and the solid catalyst was recovered by centrifugation. The reaction mixture was extracted with ethyl acetate and washed with water. The combined organic phase was then dried over Na2SO4 and concentrated under reduced pressure to give the crude residue, which was purified by column chromatography with petroleum ether/ethyl acetate to afford the pure thiocyanated product 2. The recovered catalyst was then washed with ethanol and deionized water, dried under vacuum, and reused for the next run. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With iodine; dimethyl sulfoxide at 80℃; for 12h; Inert atmosphere; Sealed tube; Green chemistry; | |
77% | With oxygen; acetic acid; potassium iodide; sodium nitrite In acetonitrile at 80℃; for 12h; Sealed tube; Green chemistry; regioselective reaction; | 3-[(3-Methoxyphenyl)thio]-1H-indole (3aa):Typical Procedure General procedure: A 15 mL tube equipped with a magnetic stirring bar wascharged with 1H-indole (0.5 mmol), sodium S-(3-methoxyphenyl)thiosulfate (0.6 mmol), KI (20 mol%), and NaNO2 (10 mol%).The tube was then sealed with a rubber plug, and MeCN (3 mL)and HOAc (0.5 mL) were injected into the tube. The air in thetube was replaced by charging with oxygen, and the mixturewas stirred under an oxygen atmosphere (balloon) at 80 °Cuntil the reaction was complete (GC). The mixture was cooledto r.t. and the solvent was removed under vacuum. The residuewas washed with 10% aq Na2S2O3 (30 mL) and extracted withCH2Cl2 (4 × 20 mL). The organic layer was then dried (Na2SO4)and concentrated under vacuum. The residue was further purifiedby flash column chromatography (silica gel, PE-Et2O) togive a light-yellow solid; yield: 92 mg (72%); mp 87.6-88.4 °C. |
77% | With oxygen; acetic acid; potassium iodide; sodium nitrite In acetonitrile at 80℃; for 12h; Sealed tube; | 15 Example 15: Preparation of 7-methyl-3-m-methoxyphenylthio-1H-indole (Formula 7) In a 15 mL glass tube, 3 mL of acetonitrile, 0.5 mmol of 7-methyl-1H-indole, 0.6 mmol of 3-methoxyphenylthiosulfate, 0.1 mmol of KI, and 0.05 mmol of NaNO2 were added. The air in the reaction tube was replaced with oxygen, and the bottle was sealed with a rubber stopper. Then, an oxygen balloon was inserted, and 0.5 mL of HOAc was added to the reaction tube by a syringe. The reaction tube was placed in an oil bath previously heated to 80 ° C, and reacted for 12 hours under stirring. . Distilled under reduced pressure, stirred with sodium thiosulfate solution, and then extracted with dichloromethane. The organic layer was separated, dichloromethane was evaporated under reduced pressure, and then purified by column chromatography to give diethyl ether / petroleum ether volume ratio 1:5 The mixture was used as an eluent, and the eluent containing the target compound was collected, and the solvent was evaporated to give 7-methyl-3-m-methoxyphenylthio-1H-indole in an isolated yield of 77%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With sodium phosphate dodecahydrate; selenium; copper(II) oxide In dimethyl sulfoxide at 110℃; for 24h; Schlenk technique; Inert atmosphere; regioselective reaction; | |
85.9% | With selenium; potassium phosphate; copper(II) oxide In dimethyl sulfoxide at 110℃; for 25h; | 14 Example 14 The compound of the above formula (II), the compound of the above formula (III), the element Se, the CuO powder and the K3P04 · 12H20 were added to the organic solvent DMS0 in the reaction vessel at room temperature. Wherein the molar ratio of the compound of the formula (II) to the compound of the formula (III) is 1: 3, the molar ratio of the compound of the formula (Π) to the element Se is 1: 3, the molar ratio of the compound of the formula (II) to CuO is 1: The molar ratio of the compound of formula (II) to K3P04 · 12H20 was 1: 1.5, and then the mixture was heated to 110 ° C under an air atmosphere and incubated for 25 hours. After the post-treatment, the product (I) as a brown liquid was obtained in a yield of 85.9% and a purity of 99.2% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With iodine In acetonitrile at 80℃; for 16h; regioselective reaction; | 2.2 General Procedure for Regioselective Synthesisof 3-Thioindoles Under Air General procedure: Acetonitrile (2 mL) was added into a mixture of indoles 1 (0.25 mmol), thiols 2 (0.375 mmol) and I2 (5 mol %) in a 25 mL round-bottomed flask at room temperature under air. The reaction vessel was allowed to stir at 80 °C for 16 h. After the reaction, the solvent was then removed under vacuum. The residue was purified by flash column chromatography using a mixture of petroleum ether and ethyl acetate as eluent to give the desired 3-thioindoles 3. The characterization of the corresponding products wasshown in Supporting Materials. |
62% | With Rose Bengal lactone at 20℃; for 12h; Irradiation; Green chemistry; | |
62% | With rose bengal In acetonitrile at 25℃; for 20h; Irradiation; | 7 Example 7 The reaction flask was charged with 0.15 mmol of 7-methylindole, 0.3 mmol of p-methylthiophenol, 0.002 mmol of rose bengal, 0.15 ml of acetonitrile and irradiated with a 400 nm light source under agitation at 25 ° C for 20 hours, after which the reaction was completed. After separation and purification by column chromatography, the target product was obtained. The volume ratio of petroleum ether and ethyl acetate in the column chromatography eluate was 20: 1 to obtain the purified target product in a yield of 62%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With iodine; oxygen; pyrographite; In N,N-dimethyl-formamide; at 120℃; for 1.5h; | General procedure: A 50 mL round bottom flask equipped with a magnetic stirring bar was charged with substituted indole 1 (1.0 mmol, 1.0 equiv), HMTA (2.0 mmol, 0.2803 g, 2.0 equiv), activated carbon (0.1 g) and DMF (2 mL). Then I2 (0.2 mmol, 0.0507g, 20 mol%) was added and the flask was equipped with a reflux condenser. The reaction mixture was stirred at 120 oC under open air and monitored by TLC. Upon completion of the reaction, the reaction mixture was cooled to room temperature. The resultant mixture was filtered through a pad of celite and the filter cake was washed thoroughly with EtOAc (4 × 6 mL). The filtrate was washed with 0.5 M aqueous HCl (10 mL), saturated NaHCO3 solution (10 mL) and saturated NaCl solution ( 10 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel eluted with hexane and ethyl acetate to give the product. |
88% | With aluminum (III) chloride; In N,N-dimethyl-formamide; at 120℃; for 1.5h; | General procedure: A method for synthesizing compound III-1 wherein R1, R2 and R3 are simultaneously hydrogen in the formula III, the method comprising the steps of:(1) Add to a 50 mL round bottom flask1.0mmol indole(In the formula I, R1, R2, and R3 are both hydrogen) and1.0 mmol (0.140 g) of hexamethylenetetramine, then 2 mL of N,N-dimethylformamide (DMF), stirred in a magnetic stirrer to dissolve the solid, followed by the addition of 0.05 mmol (0.012 g) of crystalline trichloride Aluminum, connected to a reflux condenser, heated at 120 C, the reaction progress was monitored by TLC, and the reaction was cooled to room temperature after 1 h to prepare a suspension;(2) The suspension prepared in the step (1) is suction filtered with a funnel padded with diatomaceous earth.The filter cake was washed well with ethyl acetate, suction filtered, and the above operation was repeated until the filtrate had no product, and all the filtrates were combined.Dilute with 15 mL of saturated saline solution, disperse and separate the layers, and the aqueous layer was further extracted with ethyl acetate three times.Each time 10 mL, the ethyl acetate layer was combined and washed with 10 mL of 2 mol/L diluted hydrochloric acid.Wash with 10 mL of saturated sodium bicarbonate solution, and finally wash with 10 mL of saturated brine.The washed ethyl acetate layer was dried over anhydrous sodium sulfate, and after drying, the desiccant was filtered off.Then use a rotary evaporator to recover the solvent to concentrate the product, and finally,The residue is subjected to silica gel column chromatography using a mixture of n-hexane-ethyl acetate (V/V = 2:1) as an eluent to obtain a purified product.The mass of the compound III-indole-3-carbaldehyde is 0.137g,The product yield was 94%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20%; 28% | With palladium on activated charcoal; zinc(II) oxide; In water; at 150℃; for 24.0h;Sealed tube; | General procedure: 1 mmol of amine, 0.07 mmol of Pd/C, 3 mmol of ZnO, 6 mL of distilled water and 6 mL of ethylene glycol were mixed manually inside a 20 mL Teflon flask. Then it was sealed into a steel autoclave and introduced in a preheated oven at 150 C for 24 h. The reaction mixture was cooled to room temperature, 25 mL of distilled water were added and the crude was filtered through a 0.2 mm Teflon filter. The reaction mixture was extracted with ethyl acetate3 15 ml and organic layers were combined, dried with Na2SO4, filtered and concentrated affording the reaction crude that was cheeked by NMR. Crude reaction was purified by chromatotron (1 mm, silica, from hexane to hexane/AcOEt 1:3) affording pure beta-amino alcohols. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With oxygen In tetrahydrofuran at 20℃; Irradiation; | 6 Catalytic aerobic selenization of 7-methylhydrazine with 1,2-diphenyl diselenide by CMP-CUS8-3 Add 7-methylindole (39.3 mg, 0.3 mmol) to a 25 mL single neck round bottom flask.1,2-diphenyl diselenide (156.0 mg, 0.5 mmol),And 20 mg of CMP-CSU8 and 5 mL of tetrahydrofuran solvent (THF).In an oxygen atmosphere (~1.0atm),It was irradiated with a 14 W blue LED (0.20 W/cm 2 ) at a distance of about 8 cm from the reaction device.Through TLC real-time tracking to determine the completion of the raw material reaction,Concentrate the reaction mixture,And purified by silica gel chromatography.The desired product 7-methyl-3-arylselenoindole is obtained.The yield was 99%.The reaction catalyst CMP-CUS8-3 was centrifuged.After washing with organic reagents multiple times,Vacuum drying,Continue to voteCatalytic oxidation reaction: 7-methyl hydrazine (39.3 mg, 0.3 mmol),1,2-diphenyl diselenide (156.0 mg, 0.5 mmol),5mL tetrahydrofuran solvent,Oxygen atmosphere (~0.1Mpa),Irradiated with 14W blue LED (0.20 W/cm2) at a distance of about 8 cm from the reaction device.React at room temperature for 8 h,The yield of 1-methyl-3-arylselenoindole after the catalyst cycle was 99%. |
90% | With iridium(III) bis[2-(4,6-difluorophenyl)pyridinato]picolinate In acetonitrile at 25℃; Irradiation; Green chemistry; | |
90% | With iridium(III) bis[2-(4,6-difluorophenyl)pyridinato]picolinate In acetonitrile at 20℃; Irradiation; Green chemistry; | 11 Example 11: Preparation of Compound IIIb in Table 2 below General procedure: Aromatic heterocyclic compound I (0.2 mmol), symmetrical diselenide 2 (0.12 mmol), and a solution of FIrPic (0.002 mmol) in 2 mL of anhydrous acetonitrile were placed in a clear glass tube and irradiated under a blue LED lamp. During the reaction, the progress of the reaction was checked by thin-layer chromatography. After the aromatic heterocyclic compound I completely disappeared, the solvent was removed under reduced pressure, and the residue was separated by preparative column chromatography (neutral alumina was filled, and the eluent was petroleum ether: acetic acid Ester = 30:1 isocratic elution) to give the pure asymmetric selenoether compound IIIb. |
61% | With 3-chloro-benzenecarboperoxoic acid; sodium bromide In acetonitrile at 20℃; for 24h; regioselective reaction; | A typical procedure for the preparation of 3-selenylindoles General procedure: Indoles 1 (0.2 mmol), diselenides 2 (0.11 mmol), NaBr (0.1 mmol) and mCPBA (0.24 mmol) were added successivelyto MeCN (3 mL). The suspension was vigorously stirred at r. t. for 24 h. Upon completion, the reaction was quenched by additionof sat. aq. Na2S2O3 (2 mL), and then sat. aq. Na2CO3 (8 mL) and H2O (5 mL) were added, respectively. 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 finally purified on a silica gel plate (5:1 petroleum ether-ethyl acetate) to furnish products 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With iron(III) chloride; ammonia; In water; N,N-dimethyl-formamide; at 130℃; for 1.5h; | General procedure: A 50 mL round-bottomed flask equipped with a magnetic stirringbar was charged with the appropriate indole 1 (0.5 mmol,1.0 equiv), 37% aq HCHO (0.5 mmol, 0.0406 g, 1.0 equiv), 25% aqNH3 (1.0 mmol, 0.0681 g, 2.0 equiv), FeCl3 (0.01 mmol, 0.0016 g,2 mol%), and DMF (2 mL). The flask was fitted with a reflux condenser,and the mixture was stirred at 130 C under open air.When the reaction was complete (TLC), the mixture was cooledto r.t., diluted with sat. aq NaCl (10 mL) and 0.5 M aq HCl (2 mL),and extracted with EtOAc (3 x 7 mL). The organic layers werecombined, washed with sat. aq NaHCO3 (10 mL) and sat. aq NaCl(10 mL), dried (Na2SO4), and concentrated under reduced pressure.The residue was purified by flash column chromatography(silica gel, hexane-EtOAc). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | Stage #1: 3,4-dihydroisoquinoline With methanesulfonic acid In water for 0.166667h; Green chemistry; Stage #2: 7-methyl-1H-indole With tetra-(n-butyl)ammonium iodide In water at 60℃; for 18h; Green chemistry; | 2. General procedure for the Mannich reaction General procedure: To a solution of methanesulfonic acid (0.33 mmol) in water (5 mL) was added imine 1 (0.4 mmol) under vigorous stirring. After stirring for 10 min, TBAI (0.1 mmol) and the corresponding indole (0.33 mmol) were added. The reaction mixture was stirred at 60 °C to complete the transformation (TLC monitoring). After that the reaction mixture was quenched with saturated NaHCO3 (15 mL) and extracted with ethyl acetate (3×15 mL). The combined organic extracts were dried over Na2SO4, concentrated under reduced pressure. The residue was purified by preparative thin layer chromatography silica gel plate to afford target product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With manganese(III) triacetate dihydrate; acetic acid; at 80℃; for 2h;Inert atmosphere; | General procedure: Manganese triacetate (2 mmol) is added portion wise to a pre dissolved solution of Indole (1mmol) and benzimidazolethiol (1mmol) in acetic acid (10mL) at room temperature under Nitrogen atmosphere. The reaction mixture is stirred at 80 C for 2 hours. After completion of reaction, as monitored by T.L.C analysis, the reaction mixture was quenched by the addition of water 20 ml. The organic compounds are extracted with ethyl acetate (3x20ml). The combined layers are dried over anh.Na2SO4. The required product is purified by column chromatography, eluted with 8% methanol in DCM to get the product. The product is confirmed by 1H, 13C, NMR, IR and mass |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With manganese(III) triacetate dihydrate; acetic acid; at 80℃; for 2h;Inert atmosphere; | General procedure: Manganese triacetate (2 mmol) is added portion wise to a pre dissolved solution of Indole (1mmol) and benzimidazolethiol (1mmol) in acetic acid (10mL) at room temperature under Nitrogen atmosphere. The reaction mixture is stirred at 80 C for 2 hours. After completion of reaction, as monitored by T.L.C analysis, the reaction mixture was quenched by the addition of water 20 ml. The organic compounds are extracted with ethyl acetate (3x20ml). The combined layers are dried over anh.Na2SO4. The required product is purified by column chromatography, eluted with 8% methanol in DCM to get the product. The product is confirmed by 1H, 13C, NMR, IR and mass |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64.3% | With o-toluidine; In acetonitrile; | This embodiment provides a quinone compound, and its reaction formula is:In a reaction flask, 5 mmol of <strong>[136-80-1]N-hydroxyethyl-2-methylaniline</strong> and 7.5 mmol of 2-methylaniline provided in Example 2 were weighed out and dissolved in 200 ml of acetonitrile, and Sn/activated carbon loaded catalyst was added, and TLC was used to detect N. The reaction was stopped after the reaction of hydroxyethyl-2-methylaniline was completed.After isolation and purification, 7-methylindole was obtained (yield 64.3%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With di-tert-butyl peroxide In toluene at 110℃; for 12h; Inert atmosphere; | 2.3 General Procedure fortheHeterogeneousCopper(I)-Catalyzed Decarboxylative Couplingof-Amino Acids withVarious CarbonNucleophiles. General procedure: To a 10mL reaction tube were added N,N-SBA-15-CuBr(122mg, 0.09mmol), -amino acid 1 (0.6mmol), nucleophile2 or 4 (0.9mmol), di-tert-butyl peroxide (0.84mmol),and toluene (3mL) under Ar. The reaction temperature wasraised to 110°C as soon as possible. The resulting mixturewas stirred at that temperature for 12h, and then was cooledto room temperature. The reaction mixture was diluted withEtOAc (10mL) and filtered. The N,N-SBA-15-CuBr catalystwas washed with toluene (2 × 5mL) and acetone (2 × 5mL),dried at 80°C in vacuo for 2h and reused in the next run.The filtrate was concentrated under reduced pressure, andthe residue was purified by flash silica gel column chromatography(light petroleum ether/diethyl ether) to aford thetarget product 3 or 5. |
62% | With copper carbonate hydroxide; 1,8-diazabicyclo[5.4.0]undec-7-ene In toluene at 110℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85.5% | Stage #1: 7-methyl-1H-indole With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.25h; Stage #2: benzenesulfonyl chloride In N,N-dimethyl-formamide at 0 - 20℃; for 2h; Inert atmosphere; | 1 Step 1: preparation of 7-methyl-l-(phenylsulfonyl)-lH-indole (2) To a solution of sodium hydride (0.92 g, 23 mmol) in DMF (10 mL) was added solution of 7 -methyl- lH-indole (1, 3.0 g, 23 mmol) in DMF at 0 °C, dropwise over 15 min. Benzenesulfonyl chloride in DMF (2.96 mL, 23 mmol) was added at 0°C and stirred for 2 h at room temperature under N2 atmosphere. To the reaction mixture was added ice cold water (50 mL), then filtered off the precipitate and washed with ice cold water to obtain brown solid (5.30 g, 85.50%). MS (ESI) m/z 272.1 (M+H)+. |
85.5% | Stage #1: 7-methyl-1H-indole With sodium hydride In N,N-dimethyl-formamide for 0.25h; Stage #2: benzenesulfonyl chloride In N,N-dimethyl-formamide at 0 - 20℃; for 2h; Inert atmosphere; | 1.1 Step 1: Preparation of 7-methyl-l-(phenylsulfonyl)-lH-indole (2) To a solution of sodium hydride (0.92 g, 23 mmol) in DMF (10 mL) was added solution of 7 -methyl- IH-indole (1, 3.0 g, 23 mmol) in DMF at 0 °C, dropwise over 15 min. Benzenesulfonyl chloride in DMF (2.96 mL, 23 mmol) was added at 0°C and stirred for 2 h at rt under N2atmosphere (Reaction condition a). To the reaction mixture was added ice cold water (50 mL), then filtered off the precipitate and washed with ice cold water to obtain brown solid (2) (5.30 g, 85.50%). MS (ESI) m/z 272.1 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With (R)-3,3'-bis(2,4,6-triisopropylphenyl)binol phosphoric acid In 1,3,5-trimethyl-benzene at -20℃; enantioselective reaction; | General procedure for catalytic enantioselective conjugate addition (+)-4-Methyl-N-(2-((7-methyl-1H-indol-3-yl)(phenyl)methyl)benzofuran-3-yl)benzenesulfonamide (3ah): 93 mg, 92% yield, white solid, m.p. = 190-192 °C, new compound, Rf = 0.30 (hexanes/ethyl acetate = 5:1), 98% ee, [α]20D = +116.77 (c 0.93, EtOAc). 1 H NMR (400 MHz, CDCl3) δ 7.97 (s, 1H), 7.62 (d, J = 8.1 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 7.24-7.07 (m, 8H), 7.05-6.90 (m, 4H), 6.79 (d, J = 1.6 Hz, 1H), 6.55-6.36 (m, 1H), 5.68 (s, 1H), 2.43 (s, 3H), 2.21 (s, 3H);13C NMR (100 MHz, CDCl3) δ 155.7, 153.3, 144.0, 140.2, 136.3, 135.9, 129.6, 128.6, 128.4, 127.6, 126.9, 126.2, 126.1, 124.4, 123.3, 123.2, 122.9, 120.5, 120.0, 119.7, 117.3, 115.7, 113.0, 111.6, 39.9, 21.5, 16.6. HPLC: Chiralcel AD-H column, 254 nm, 30 °C, n-hexane/i-PrOH = 60/40, flow = 0.8 mL/min, retention time 12.8 min and 15.6 min (major). HRMS calculated for C31H25N2O3S [M-H]- 505.1591, found: 505.1604. |
92% | With (R)-3,3'-bis(2,4,6-triisopropylphenyl)binol phosphoric acid In 1,3,5-trimethyl-benzene at -20℃; | 21 General procedure: Add azadiene, chiral phosphoric acid A1 and mesitylene into the reaction flask, put it in a cold bath at -20°C, then add indole, stir and react for 48-72h, direct column chromatography (volume ratio of eluent petroleum ether and ethyl acetate is 5:1) to obtain the corresponding chiral heterotriarylmethane compound; the molar ratio of the azadiene, asymmetrically added indole and the catalyst is 1:1.0:0.05. The yield is the isolated yield, and the enantiomeric excess of the product is determined by chiral liquid chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With (R)-3,3'-bis(2,4,6-triisopropylphenyl)binol phosphoric acid In 1,3,5-trimethyl-benzene at -20℃; enantioselective reaction; | General procedure for catalytic enantioselective conjugate addition (S)-(-)-N-(2-((1H-Indol-3-yl)(phenyl)methyl)benzofuran-3-yl)-4-methylbenzenesulfonamide (3fh): 104 mg, 93% yield, pink solid, m.p. = 145-146 °C, new compound, Rf = 0.50 (hexanes/ethyl acetate = 5:1), 99% ee, [α]20D = -92.99 (c 0.40, EtOAc). 1 H NMR (400 MHz, CDCl3) δ 7.93 (s, 1H), 7.86 (d, J = 8.5 Hz, 2H), 7.75 (d, J = 8.2 Hz, 1H), 7.55 (d, J = 8.3 Hz, 2H), 7.52-7.42 (m, 2H), 7.41-7.35 (m, 1H), 7.33-7.27 (m, 2H), 7.25-7.12 (m, 3H), 7.04 (d, J = 7.8 Hz, 1H), 6.99 (d, J = 7.0 Hz, 1H), 6.93 (t, J = 7.7 Hz, 3H), 6.57 (d, J = 1.8 Hz, 1H), 6.35 (s, 1H), 6.00 (s, 1H), 2.46 (s, 3H), 2.16 (s, 3H);13C NMR (100 MHz, CDCl3) δ 154.4, 153.4, 144.0, 136.4, 136.1, 136.0, 134.0, 131.4, 129.6, 128.9, 127.9, 127.6, 126.4, 126.4, 126.4, 126.0, 125.7, 125.6, 124.5, 124.1, 123.7, 123.3, 123.2, 120.6, 120.3, 120.1, 116.8, 115.6, 114.0, 111.6, 36.8, 21.6, 16.7. HPLC: Chiralcel IC column, 254 nm, 30 °C, n-hexane/i-PrOH = 90/10, flow = 0.7 mL/min, retention time 18.0 min (major) and 21.1 min. HRMS calculated for C35H32N3O3S [M+NH4]+ 574.2159, found: 574.2161. |
93% | With (R)-3,3'-bis(2,4,6-triisopropylphenyl)binol phosphoric acid In 1,3,5-trimethyl-benzene at -20℃; | 36 General procedure: Add azadiene, chiral phosphoric acid A1 and mesitylene into the reaction flask, put it in a cold bath at -20°C, then add indole, stir and react for 48-72h, direct column chromatography (volume ratio of eluent petroleum ether and ethyl acetate is 5:1) to obtain the corresponding chiral heterotriarylmethane compound; the molar ratio of the azadiene, asymmetrically added indole and the catalyst is 1:1.0:0.05. The yield is the isolated yield, and the enantiomeric excess of the product is determined by chiral liquid chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With (R)-3,3'-bis(2,4,6-triisopropylphenyl)binol phosphoric acid In 1,3,5-trimethyl-benzene at -20℃; enantioselective reaction; | General procedure for catalytic enantioselective conjugate addition (+)-N-(2-((4-Chlorophenyl)(7-methyl-1H-indol-3-yl)methyl)benzofuran-3-yl)-4-methylbenzenesulfonamide (3jh): 100 mg, 92% yield, pink solid, m.p. = 124-126 °C, new compound, Rf = 0.45 (hexanes/ethyl acetate = 5:1), 98% ee, [α]20D = +102.66 (c 0.30, EtOAc). 1 H NMR (400 MHz, CDCl3) δ 7.96 (s, 1H), 7.60 (d, J = 7.3 Hz, 2H), 7.35 (d, J = 8.4 Hz, 1H), 7.24-7.15 (m, 4H), 7.13-6.93 (m, 8H), 6.85 (s, 1H), 6.26 (s, 1H), 5.69 (s, 1H), 2.47 (s, 3H), 2.24 (s, 3H);13C NMR (100 MHz, CDCl3) δ 155.5, 153.4, 144.2, 138.8, 136.4, 136.0, 132.7, 130.0, 129.7, 128.6, 127.7, 126.0, 126.0, 124.6, 123.3, 123.2, 123.2, 120.5, 120.3, 119.5, 117.2, 115.6, 113.1, 111.7, 39.2, 21.5, 16.7. HPLC: Chiralcel AD-H column, 254 nm, 30 °C, n-hexane/i-PrOH = 75/25, flow = 0.8 mL/min, retention time 29.1 min and 31.4 min (major). HRMS calculated for C31H29ClN3O3S [M+NH4]+ 558.1613, found: 558.1614. |
92% | With (R)-3,3'-bis(2,4,6-triisopropylphenyl)binol phosphoric acid In 1,3,5-trimethyl-benzene at -20℃; | 37 General procedure: Add azadiene, chiral phosphoric acid A1 and mesitylene into the reaction flask, put it in a cold bath at -20°C, then add indole, stir and react for 48-72h, direct column chromatography (volume ratio of eluent petroleum ether and ethyl acetate is 5:1) to obtain the corresponding chiral heterotriarylmethane compound; the molar ratio of the azadiene, asymmetrically added indole and the catalyst is 1:1.0:0.05. The yield is the isolated yield, and the enantiomeric excess of the product is determined by chiral liquid chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With copper(II) ferrite; lithium tert-butoxide In neat (no solvent) at 80℃; for 24h; | 2.1. General procedure 1 for the synthesis of compounds 1-11, 16-20 General procedure: A mixture of Indole (0.3 mmol), Alcohol (1.2 mmol), CuFe2O4 (7.2mg, 10 mol%) and LiOtBu (24 mg, 1 equiv.) were charged in a pressuretube. The pressure tube was immersed in a pre-heated oil bath at 80 Cand stirred for 24 h. After cooling, the reaction mixture was filtered overa plug of Celite with hot water to eliminate the excess of alcohol. Theorganic phase was washed by Ethyl acetate, then dried by sodium sulfate(Na2SO4). The concentrated residue was purified by column chromatography(Hexane/Ethyl acetate). |
91% | With copper diacetate; lithium tert-butoxide In neat (no solvent) at 100℃; for 24h; | General procedure for the synthesis of compounds 1-15: General procedure: A mixture of indole (0.3 mmol), Cu(OAc)2 (2.72 mg, 5 mol%), LiOt-Bu (24 mg, 1 equiv.) and benzyl alcohol (0.9 mmol) were charged in a 25 mL round bottom flask. Every 4 flasks were attached to a Buechi distillation spider connected to a 3W air pump (See Scheme 1). Reaction system was designed with a small air outlet on top of system (See SI). All reaction flasks were immersed in a pre-heated oil bath at 100C and stirred for 24h. After cooling, the reaction mixture was filtered over a plug of Celite with hot water to eliminate the excess of benzyl alcohol. Then, ethyl acetate was added into the organic phase and this mixture was dried by sodium sulfate (Na2SO4). The concentrated residue was purified by column chromatography (Hexane/Ethyl acetate). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With C9H18NO(1+)*BH4(1-) In tetrahydrofuran at 0℃; | General procedure B: General procedure: To a solution of 1 (0.1 mmol) and 4 (0.2 mmol) in THF (1.0 mL) was addedTEMPO+BF4- (0.1 mmol) at 0 °C. The mixture was further stirred until the disappearance of startingmaterial 1 by TLC analysis at 0 °C. The solvent was removed and the residue was purified by flashchromatography using acetone-petroleum ether as eluent to aord the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With C9H18NO(1+)*BH4(1-) In tetrahydrofuran at 20℃; for 6h; | General procedure D: General procedure: To a solution of C2-substituted indole (0.2 mmol) or indole (0.3 mmol) inTHF (1.0 mL) was added TEMPO+BF4- (0.1 mmol). The mixture was stirred at room temperature for 6 h. The solvent was removed and the residue was purified by flash chromatography usingacetone-petroleum ether as eluent to aord the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With copper diacetate; bis-diphenylphosphinomethane; potassium hydroxide In neat (no solvent) at 160℃; for 12h; Inert atmosphere; chemoselective reaction; | General procedure for the synthesis of compounds 1-18 General procedure: A mixture of indole (0.5 mmol, 58.6 mg), Cu(OAc)2 (4.54 mg, 5 mol%), dppm (9.6 mg, 5 mol%), KOH (56 mg, 2 equiv.) and benzyl alcohol (0.5 mL, about 5 mmol) were charged in a pressure tube under argon. The pressure tube was immersed in a pre-heated oil bath at 160 °C and stirred for 12 h. After cooling, the reaction mixture was filtered over a plug of Celite with hot water to eliminate the benzaldehyde and the excess of benzyl alcohol. Ethyl acetate was added into the organic phase and this mixture was dried by sodium sulfate (Na2SO4). The concentrated residue was purified by column chromatography (Hexane/ethyl acetate). |
89% | With C18H18Cl4N2Ni2O2; potassium 2-methylbutan-2-olate In neat (no solvent) at 140℃; for 6h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With caesium carbonate In acetonitrile at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With potassium fluoride; di-tert-butyl peroxide; oxygen In toluene at 100℃; for 3h; | General Procedure for preparing diphenylurea derivatives 3 General procedure: Indole (1.0 mmol), 2,4-pentanedione (1.0 mmol), KF (1 mmol), DTBP (2 mmol) and methylbenzene (20 mL) were charged into a 25 mL round-bottom flask, and the mixture was refluxed. The resulting solution was stirred for 3 h until the indole were not consumed. The mixture was cooled to room temperature, then EtOAc (50 mL × 2) was added. The organic phase was washed with water (20 mL), dried over Na2SO4, concentrated and purified by flash column chromatography to afford 3-(3-oxoindolin-2-ylidene)pentane-2,4-dione in a 74% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃; for 2h; | I. Deprotection of 7-substituted indole: General procedure: Into a single-necked round bottomed flask, equipped with a magnetic stirrer bar and dryingtube, was taken a solution of C-7 substituted protected indole 3 (0.25 g, 1 equiv) in dry THF(10 mL), to this solution lithium aluminium hydride (1.1 equiv) was added 0 °C. Ice bath wasremoved and reaction mixture was stirred at room temperature for 2 hr. Reaction was quenchedwith 15% sodium hydroxide solution (5 mL) and extracted with chloroform (3 x 10 mL). Theorganic layer was washed with brine, dried over anhydrous sodium sulphate and solvent wasevaporated under reduced pressure to afford the crude product which was purified by columnchromatography using silica ge |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With selenium; sodium t-butanolate In acetonitrile at 40℃; for 6h; Sealed tube; | 3.1. 0.3 mmol scale General procedure: To a 8.0-mL scintillation vial equipped with a magnetic stirrer, indole 1a (0.36 mmol, 1.2 equiv.), selenium powder 2 (0.36 mmol, 1.2 equiv.), t-BuONa (0.45 mmol, 1.5 equiv.), solvent CH3CN (1.0 mL) and (3-bromopropyl)benzene 3a (0.30 mmol, 1.0 equiv.) sequentially added at room temperature. The vial was sealed with a screw-top septum cap and placed in a heating block that was preheated to 40 °C for 6h. After the indicated reaction time, an aqueous saturated NH4Cl solution and EtOAc were added and the layers were separated. The aqueous phase was extracted with EtOAc (x 3) and the combined organic layers were dried over Na2SO4 and concentrated. The residue was purified by flash column chromatography on silica gel (eluent: Petroleum ether/EtOAc) to give the target product 4aa as a Colorless oil. |
Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
Home
* Country/Region
* Quantity Required :
* Cat. No.:
* CAS No :
* Product Name :
* Additional Information :