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CAS No. : | 5825-62-7 | MDL No. : | MFCD00031388 |
Formula : | C7H8N2O4S | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | AXEHDVUAWILBRN-UHFFFAOYSA-N |
M.W : | 216.21 | Pubchem ID : | 4689022 |
Synonyms : |
|
Num. heavy atoms : | 14 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.14 |
Num. rotatable bonds : | 3 |
Num. H-bond acceptors : | 4.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 53.53 |
TPSA : | 100.37 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.87 cm/s |
Log Po/w (iLOGP) : | 0.71 |
Log Po/w (XLOGP3) : | 1.05 |
Log Po/w (WLOGP) : | 1.86 |
Log Po/w (MLOGP) : | -0.39 |
Log Po/w (SILICOS-IT) : | -1.74 |
Consensus Log Po/w : | 0.3 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.96 |
Solubility : | 2.36 mg/ml ; 0.0109 mol/l |
Class : | Very soluble |
Log S (Ali) : | -2.75 |
Solubility : | 0.386 mg/ml ; 0.00178 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -2.15 |
Solubility : | 1.53 mg/ml ; 0.0071 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 2.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 2.16 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H319 | 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 |
---|---|---|
With sulfuric acid; nitric acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With hydrogen;5%-palladium/activated carbon; In tetrahydrofuran; at 25℃; under 760.051 Torr; for 96h; | 5% Palladium on carbon ("wet", 11.1 g) was added to a solution of N-(4-nitro- phenyl)-methanesulfonamide (111.4 g, 0.52 mol) in tetrahydrofuran (900 mL) at 25 0C. The atmosphere above the resulting suspension was replaced with hydrogen gas and the reaction mixture was maintained under 1 atmosphere of hydrogen at 25 0C for 4 days using several balloons. The mixture was then filtered through Celite and the Celite was washed with tetrahydrofuran (3 x 100 mL). The combined filtrate and washings were concentrated in vacuo to approximately 300 mL volume and heptane (500 mL) was added dropwise via addition funnel over 45 min at 25 0C with vigorous stirring. The resulting suspension was stirred for an additional 45 min at 25 0C, and then was filtered through medium paper using a Buchner funnel. The collected solid was washed with heptane (1 x 150 mL) and was air-dried to afford the desired product, N-(4-amino-phenyl)-methanesulfonamide (90.7 g, 0.49 mol, 95%) as a beige powder. 1H nuMR (400 MHz, OMSO-d6) delta 2.79 (3H, s), 5.00 (2H, s), 6.49 (2H, d, / = 8.5 Hz), 6.87 (2H, d, / = 8.6 Hz), 8.87 (IH, s). |
95% | With hydrogen;5%-palladium/activated carbon; In tetrahydrofuran; at 25℃; under 760.051 Torr; for 96h;Product distribution / selectivity; | 5% Palladium on carbon ("wet", 11.1 g) was added to a solution of N-(4-nitro- phenyl)-methanesulfonamide (Example 3a', 111.4 g, 0.52 mol) in tetrahydrofuran (900 mL) at 25 0C. The atmosphere above the resulting suspension was replaced with hydrogen gas and the reaction mixture was maintained under 1 atmosphere of hydrogen at 25 0C for 4 days using several balloons. The mixture was then filtered through Celite and the Celite was washed with tetrahydrofuran (3 x 100 mL). The combined filtrate and washings were concentrated in vacuo to approximately 300 mL volume and heptane (500 mL) was added dropwise via addition funnel over 45 min at 25 0C with vigorous stirring. The resulting suspension was stirred for an additional 45 min at 25 0C, and then was filtered through medium paper using a Buchner funnel. The collected solid was washed with heptane (1 x 150 mL) and was air-dried to afford the desired product, N-(4-amino-phenyl)-methanesulfonamide (90.7 g, 0.49 mol, 95% yield) as a beige powder. 1H nuMR (400 MHz, DMSO-^) delta 2.79 (3 H, s), 5.00 (2H, s), 6.49 (2H, d, J= 8.5 Hz), 6.87 (2H, d, J= 8.6 Hz), 8.87 (IH, s). |
71% | With hydrogen;palladium 10% on activated carbon; In methanol; ethyl acetate; N,N-dimethyl-formamide; at 20 - 50℃; for 4.5h; | [0364] N-(4-Amino-phenylVmethanesulfonamide (83a).; N-(4-Nitro-phenyl)-methanesulfonamide (82a) (25 g, 115.62 mmol) was dissolved in N,N-dimethylformamide (15 mL) with gentle heating to ~500C via heat gun. Ethyl acetate (100 mL) and methyl alcohol (100 mL) were added followed by 10% palladium on carbon (4 g). The mixture was degassed while stirring and the flask was charged with hydrogen gas via balloon. The mixture stirred at room temperature for 4.5 hours. The mixture was filtered through celite (rinsed with ethyl acetate) and concentrated in vacuo to a yellow green solution with a volume of ~10 mL. Methylene chloride (-50 mL) was added and a solid began to precipitate. The mixture stirred at room temperature for 30 minutes. The solid was collected by vacuum filtration and dried in vacuo to afford the desired product, N-(4-amino- phenyl)-methanesulfonamide 83a (15.32 g, 71 % yield) as a beige powder. 1HNMR (400 MHz, DMSO-d6) delta: 2.79 (s, 3H), 5.00 (s, 2H), 6.49 (d, 2H, J= 8.5 Hz), 6.87 (d, 2H, J= 8.6 Hz), 8.87 (s, IH). |
71% | With hydrogen;palladium 10% on activated carbon; In methanol; ethyl acetate; N,N-dimethyl-formamide; at 25 - 50℃; for 4.5h;Product distribution / selectivity; | N-(4-Nitro-phenyl)-methanesulfonamide (Example 3a, 25 g, 115.62 mmol) was dissolved in N,N-dimethylformamide (15 mL) with gentle heating to -50 0C via heat gun. Ethyl acetate (100 mL) and methanol (100 mL) were added followed by 10% palladium on carbon (4 g). The mixture was degassed while stirring and the flask was charged with hydrogen gas via balloon. The mixture was stirred at 25 0C for 4.5 h. The mixture was filtered through Celite (rinsed with ethyl acetate) and concentrated in vacuo to a yellow green solution with a volume of -10 mL. Dichloro methane (-50 mL) was added and a solid began to precipitate. The mixture was stirred at 25 0C for 30 min. The solid was collected by vacuum filtration and dried in vacuo to afford the desired product, N-(4-amino-phenyl)-methanesulfonamide (15.32 g, 82.26 mmol, 71 % yield) as a beige powder. 1H nuMR (400 MHz, DMSO- d6) delta 2.79 (3H, s), 5.00 (2H, s), 6.49 (2H, d, J= 8.5 Hz), 6.87 (2H, d, J= 8.6 Hz), 8.87 (IH, s). |
71% | With hydrogen;palladium 10% on activated carbon; In methanol; ethyl acetate; N,N-dimethyl-formamide; at 25℃; for 4.5h; | N-(4-Aminophenyl)methanesulfonamide N-(4-nitrophenyl)methanesulfonamide (25 g, 115.62 mmol) was dissolved in N,N-dimethylformamide (15 mL) with gentle heating to ~50 C. via heat gun. Ethyl acetate (100 mL) and methanol (100 mL) were added followed by 10% palladium on carbon (4 g). The mixture was degassed while stirring and the flask was charged with hydrogen gas via balloon. The mixture stirred at 25 C. for 4.5 hours. The mixture was filtered through celite (rinsed with ethyl acetate) and concentrated in vacuo to a yellow green solution with a volume of ~10 mL. Dichloromethane (~50 mL) was added and a solid began to precipitate. The mixture stirred at 25 C. for 30 minutes. The solid was collected by vacuum filtration and dried in vacuo to afford the desired product, N-(4-aminophenyl)methanesulfonamide (15.32 g, 82.26 mmol, 71% yield) as a beige powder 1H NMR (400 MHz, DMSO-d6) delta 2.79 (3H, s), 5.00 (2H, s), 6.49 (2H, d, J=8.5 Hz), 6.87 (2H, d, J=8.6 Hz), 8.87 (1H, s). |
67% | With palladium 10% on activated carbon; hydrogen; In methanol; at 20℃; for 16h; | To a solution of intermediate compound 8 (3.23 mmol, 0.70 g) in MeOH (7 ml_) Pd/C 10 % (10% w/w, 70 mg) was added and the mixture was hydrogenated at room temperature for 16 hours. After that, the reaction mixture was filtered through a pad of Celite washing with THF. The solvent was evaporated under vacuum to give the title compound which was used at the next step without further purification. (0.4 g. Yield= 67%) 1 H NMR (400 MHz, DMSO-d6) delta 8.95 (1 H, brs), 6.94 (2H, d, J = 8.8 Hz), 6.56 (2H, d, J = 8.8 Hz), 5.06 (1 H, brs), 2.85 (3H, s). LC-MS: tR =0.36 [M+H]+= 187 (method 3) |
49% | With palladium 10% on activated carbon; ammonium formate; In methanol; at 45℃;Inert atmosphere; Cooling with ice; | To a solution of N-(4-nitrophenyl)methanesulfonamide (23.0 g, 106.48 mmol) in MeOH (100 mL) was added 10% Pd/C (3.0 g) purged with N2. Then a solution of HCO2NH4 (67.0 g, 1.06 mol) in MeOH (500 mL) was added gradually under ice-water bath during 5 min. After addition, the mixture was warmed to 45 C, stirred overnight, and then filtered. The filtrate was evaporated under reduced pressure to afford yellow solid which was washed with EA (500 mL x 3). The combined organic layers were evaporated under reduced pressure, purified by silica gel column chromatography (PE:EA = 1:2) to afford N-(4-aminophenyl)methanesulfonamide as a yellow solid (9.80 g, yield 49%). |
49% | With palladium 10% on activated carbon; ammonium formate; In methanol; at 45℃;Inert atmosphere; Cooling with ice; | Compound 23-3, R?H (0438) To a solution of 23-2, R?H (23.0 g, 106.48 mmol) in MeOH (100 mL) was added 10% Pd/C (3.0 g) purged with N2. Then a solution of HCO2NH4 (67.0 g, 1.06 mol) in MeOH (500 mL) was added gradually under ice-water bath during 5 min. After addition, the mixture was warmed to 45 C. and stirred overnight and filtered. The filtrate was evaporated under reduced pressure to afford yellow solid which was washed with EA (500 mL×3). The combined organic layers were evaporated under reduced pressure, purified by silica gel column chromatography (PE:EA=1:2) to afford N-(4-aminophenyl)methanesulfonamide as a yellow solid (9.80 g, yield 49%). |
With iron; ammonium chloride; In ethanol; water; for 2h;Reflux; | [0007901 To a stirred solution of compoundS (0.8 g, 1 eq) in ethanol (20 mL), iron powder (1.03 g, 5 eq), water (20 mL) and ammonium chloride (0.98 g,5 eq) were added slowly. The reaction mixture was heated to reflux for 2 h. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was filtered through celite and evaporated under reduced pressure. The residue was dissolved in ethyl acetate (50 mL) and washed with brine. The organic extract was dried over anhydrous sodium sulfate and evaporated under reduced pressure to afford the title compound 6.?H NMR (400 MHz, DMSO-d6) oe:8.89 (s, 1H), 6.88 (d, J= 8.0 Hz, 2H), 6.50(d, J= 8.8 Hz, 2H), 5.01 (s, 2H), 2.79(s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With sodium hydroxide In water for 0.5h; | |
With tributyl-amine; toluene |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With pyridine | |
95% | With pyridine at 20 - 25℃; for 2.5h; | |
95% | With pyridine In dichloromethane at 0 - 20℃; for 4h; | To a solution of pyridine (50 mL) and MsCl (15.86 g, 139.13 mmol) in DCM (150 mL) was added the solution of 4-nitrobenzenamine (16.0 g, 115.94 mmol) in pyridine (100 mL) at 0°C. The mixture was stirred at room temperature for 4 h. The volatiles were removed under reduced pressure. The residue was rinsed with water (200 mL x 3) and dried under reduced pressure to afford N-(4-nitrophenyl)methanesulfonamide as a yellow powder (23.20 g, yield 95%). |
95% | With pyridine In dichloromethane at 0 - 20℃; for 4h; | 1 Compound 23-2, R═H (0437) To a solution of pyridine (50 mL) and MsCl (15.86 g, 139.13 mmol) in DCM (150 mL) was added the solution of 4-nitrobenzenamine (16.0 g, 115.94 mmol) in pyridine (100 mL) at 0° C. The mixture was stirred at room temperature for 4 h. The volatiles were removed under reduced pressure. The residue was rinsed with water (200 mL×3) and dried under reduced pressure to afford the title compound as a yellow powder (23.20 g, yield 95%). |
89% | With pyridine In acetonitrile at 23℃; for 19h; | |
89% | Stage #1: methanesulfonyl chloride In acetonitrile for 0.666667h; Stage #2: 4-nitro-aniline With pyridine In water; acetonitrile at 25℃; for 19.5h; | 1.a A solution of methanesulfonylchloride (47.1 mL, 0.61 mol) in acetonitrile (160 mL) was added over 40 min to a solution of 4-nitroaniline (80.0 g, 0.58 mol) and pyridine (70.2 mL, 0.87 mol) in acetonitrile (400 mL) at 25 0C. The mixture was stirred at 25 0C for 19 h, and then water (800 mL) was added. The resulting suspension was stirred at 25 0C for 30 min, and then was filtered through medium paper using a Bchner funnel. The collected solid was washed with water (2 x 150 mL) and air-dried overnight to afford the desired product, N-(4-nitro-phenyl)- methanesulfonamide (111.4 g, 0.52 mol, 89%) as a pale yellow solid. 1H νMR (400 MHz, DMSOd6) δ 3.17 (3H, s), 7.35 (2H, d, / = 9.4 Hz), 8.20 (2H, d, / = 9.1 Hz), 10.69 (IH, s). |
89% | With pyridine In acetonitrile at 25℃; for 19h; | 3.d.(a)'; 4(b) A solution of methanesulfonylchloride (47.1 mL, 0.61 mol) in acetonitrile (160 mL) was added over 40 min to a solution of 4-nitro aniline (80.0 g, 0.58 mol) and pyridine (70.2 mL, 0.87 mol) in acetonitrile (400 mL) at 25 0C. The mixture was stirred at 25 0C for 19 h, and then water (800 mL) was added. The resulting suspension was stirred at 25 0C for 30 min, and then was filtered through medium paper using a Buchner funnel. The collected solid was washed with water (2 x 150 mL) and air-dried overnight to afford the desired product, N-(4-nitro-phenyl)- methanesulfonamide (111.4 g, 0.52 mol, 89% yield) as a pale yellow solid. 1H νMR (400 MHz, OMSO-d6) δ 3.17 (3H, s), 7.35 (2H, d, J= 9.4 Hz), 8.20 (2H, d, J= 9.1 Hz), 10.69 (IH, s). |
83% | With pyridine In dichloromethane at 0 - 20℃; Inert atmosphere; | 6.1.1. [(4-Bromomethylphenyl)methanesulfonylamino]acetic acid methyl ester (16a) General procedure: Methanesulfonyl chloride (3.41 mL, 44 mmol) was added dropwiseto p-toluidine (4.28 g, 40 mmol) and pyridine (3.54 mL,44 mmol) in DCM (50 mL) at 0 C under nitrogen. After addition,the mixture was warmed to room temperature and stirred overnight.The reaction was quenched with NaOH (6 mol/L) andenough water added to dissolve the resultant anion. The layerswere separated and the aqueous layer washed with DCM(20 mL). The aqueous layer was cooled (0 C) and acidified to pH2.0 by using 18% aqueous HCl. The product precipitates were filteredand washed with cold water and air-dried to constant weightto afford 4.68 g of 14a (57%) as a colorless solid. |
75% | With pyridine In dichloromethane at 20℃; | |
75% | With pyridine In dichloromethane at 0 - 20℃; Inert atmosphere; | |
64% | With pyridine at 20℃; for 24h; | 18-1 [0363] N-(4-Nitro-phenvD-methanesulfonamide (82a).; 4-Nitro-phenylamine (25 g, 181 mmol) was dissolved in pyridine (450 mL). Methanesulfonyl chloride (36a) (14.0 mL, 181 mmol) was added dropwise while stirring. The mixture stirred for 24 hours at room temperature. The solution was concentrated in vacuo to a volume of ~50 mL. The mixture was diluted with ethyl acetate (400 mL), washed with IM aqueous hydrochloric acid (5 x 200 mL). The combined aqueous layers were back extracted with ethyl acetate (200 mL). The combined organic layers were dried over magnesium sulfate and concentrated in vacuo to a volume of -250 mL. The product precipitated and was collected by vacuum filtration. The filtrate was concentrated in vacuo to about half volume and additional product precipitated. The solid was collected by vacuum filtration. The solids were combined to afford the desired product 82a, N-(4-nitro-phenyl)- methanesulfonamide (25 g, 64 % yield). 1HNMR (400 MHz, DMSO-(I6) δ: 3.17 (s, 3H), 7.35 (d, 2H, J= 9.4 Hz), 8.20 (d, 2H, J= 9.1 Hz), 10.69 (s, IH). |
64% | With pyridine at 25℃; for 16h; | 3.a; 4(a) 4-Nitro-phenylamine (25 g, 181 mmol) was dissolved in pyridine (450 mL). Methanesulfonyl chloride (14.0 mL, 181 mmol) was added dropwise while stirring. The mixture was stirred for 16 h at 25 0C. The solution was concentrated in vacuo to a volume of -50 mL. The mixture was diluted with ethyl acetate (400 mL), washed with 1.0 M aqueous hydrochloric acid solution (5 x 200 mL). The combined aqueous layers were back-extracted with ethyl acetate (200 mL). The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo to a volume of -250 mL. The product precipitated and was collected by vacuum filtration. The filtrate was concentrated in vacuo to a volume of -125 mL upon which additional product precipitated. The solid was collected by vacuum filtration. The solids were combined to afford the desired product, N-(4-nitro-phenyl)-methanesulfonamide (25 g, 115.62 mmol, 64% yield) as a pale yellow solid. 1H νMR (400 MHz, DMSO-^) δ 3.17 (3H, s), 7.35 (2H, d, J= 9.4 Hz), 8.20 (2H, d, J= 9.1 Hz), 10.69 (IH, s). |
64% | With pyridine at 25℃; for 16h; | 4 N-(4-Nitrophenyl)methanesulfonamide 4-Nitrophenylamine (25 g, 181 mmol) was dissolved in pyridine (450 mL). Methanesulfonyl chloride (14.0 mL, 181 mmol) was added dropwise while stirring. The mixture stirred for 16 hours at 25° C. The solution was concentrated in vacuo to a volume of ~50 mL. The mixture was diluted with ethyl acetate (400 mL), washed with 1 M aqueous hydrochloric acid (5*200 mL). The combined aqueous layers were back-extracted with ethyl acetate (200 mL). The combined organic layers were dried over magnesium sulfate and concentrated in vacuo to a volume of ~250 mL. The product precipitated and was collected by vacuum filtration. The filtrate was concentrated in vacuo to a volume of ~125 μL upon which additional product precipitated. The solid was collected by vacuum filtration. The solids were combined to afford the desired product, N-(4-nitrophenyl)methanesulfonamide (25 g, 115.62 mmol, 64% yield) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 3.17 (3H, s), 7.35 (2H, d, J=9.4 Hz), 8.20 (2H, d, J=9.1 Hz), 10.69 (1H, s). |
42% | With pyridine In dichloromethane at 20℃; for 48h; | |
With pyridine | ||
With triethylamine; toluene | ||
In pyridine at 28℃; for 5h; | ||
With pyridine In dichloromethane at 20℃; | ||
With pyridine | ||
With triethylamine In dichloromethane at 0 - 20℃; for 16h; Cooling with ice; | Intermediate compound 8: N-(4-nitrophenyl)-methanesulfonamide To a solution of 4-nitroaniline (7.24 mmol, 1 g) in DCM (10 mL) at 05C in an ice- bath, triethylamine (23.7 mmol, 3.3 mL) has been added under stirring. To this mixture a solution of methanesulphonyl chloride (23.7 mmol, 1 .8 mL) has been added dropwise. The mixture was left to stir at room temperature 16 h. The reaction mixture was neutralized with saturated aqueous solution of NH4CI. The organic phase was separated, and, after evaporation of the solvent, the residue was washed with ethanol and filtered to give an bissulphonamide intermediate which was dissolved in a mixture ethanohwater (2:1 , 36 mL). LiOH (39.1 mmol, 0.93 mg) was added to the solution and the reaction mixture was refluxed for two hours. After cooling at room temperature, the reaction mixture was neutralized with aqueous solution of NH4CI and the aqueous phase was extracted with DCM. The organic phase was separated and dried over anhydrous sodium sulfate, filtered and concentrated under vacuum to give the title compound which was used in the next step without further purification. (1 .3 g. Yield= 83%) 1 H NMR (400 MHz, CDCI3) δ 8.26 (2H, d, J = 9.2 Hz), 7.31 (2H, d, J = 8.8 Hz), 3.15 (3H, s). LC-MS: tR =2.28 [M+H]+= 215 (method 3) | |
With silica gel at 20℃; | ||
With pyridine In dichloromethane for 2h; | 359.1 Step 1: Synthesis of N-(4-nitrophenyl) methane sulfonamide (5): [0007891 To a stirred solution of compound 2 (2 g, 1.2 eq) in dichloromethane (20 mL), methane sulfonyl chloride (3 g, 1 eq) and pyridine were added at 0 °C and stirred at same temperature for 2 h. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was diluted with water (20 mL) and extracted with dichloromethane (2 X 25 mL). Combined organic extracts were washed with brine, dried over anhydrous sodium sulfate and evaporated under reduced pressure to afford the crude product 5. | |
With pyridine In dichloromethane | ||
With 1,4-dioxane; pyridine | ||
With pyridine In dichloromethane at 20℃; for 8h; | 31B Step B: N-(4-Nitrophenyl)methanesulfonamide 4-Nitroaniline (1.0 g) and pyridine (0.63 g, 1.1 equiv) were dissolved in 20 ml of dichloromethane, then the solution was placed in an ice bath, and methanesulfonyl chloride (0.83 g, 1 equiv) was added. The reaction was carried out for 8 hours at room temperature, and dichloromethane (50 ml) was added to the solution after the reaction to be diluted, and then water was added thereto, followed by extraction with dichloromethane. The extracted dichloromethane layer was washed successively with dilute hydrochloric acid, washed with brine, dried over anhydrous sodium sulfate and then evaporated.The solid was obtained directly for the next reaction. | |
With pyridine In dichloromethane at 20℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine In chloroform |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | In tetrahydrofuran for 5.5h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In benzene at 40℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In N,N-dimethyl-formamide for 48h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
p-Nitroanilin, CH3SO2Cl; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine In methanol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 98 percent / H2 / Pd/C / methanol 2: 94 percent / CH2Cl2 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: Et3N / methanol 2: 16 percent / TfOH / CH2Cl2 / 2 h / 0 °C 3: KOH / dimethylsulfoxide / 80 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: Et3N / methanol 2: 16 percent / TfOH / CH2Cl2 / 2 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: Fe, ferric chloride 2: ethanol / 2 h / Ambient temperature 3: K2CO3 / acetonitrile / 2 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: Fe, ferric chloride 2: ethanol / 2 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: Fe, ferric chloride 2: ethanol / 2 h / Ambient temperature 3: K2CO3 / acetonitrile / 2 h 4: DBU / acetonitrile |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: H2, / Raney nickel / methanol / 760 Torr 2: 3.8 g / N,N-dimethylaniline / acetonitrile / 4 h / 28 °C 3: lead tetraacetate / CH2Cl2 / 4 h / 15 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: H2, / Raney nickel / methanol / 760 Torr 2: N,N-dimethylaniline / acetonitrile / 16 h / 28 °C 3: lead tetraacetate / CH2Cl2 / 4 h / 15 °C 4: 51 percent / acetic acid; H2O / 0.5 h / 28 °C / temperature raised to 70-80 deg C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: H2, / Raney nickel / methanol / 760 Torr 2: 3.8 g / N,N-dimethylaniline / acetonitrile / 4 h / 28 °C 3: lead tetraacetate / CH2Cl2 / 4 h / 15 °C 4: 39.9 percent / acetic acid; H2O / 0.5 h / 28 °C / temperature raised to 70-80 deg C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: H2, / Raney nickel / methanol / 760 Torr 2: N,N-dimethylaniline / acetonitrile / 16 h / 28 °C 3: lead tetraacetate / CH2Cl2 / 4 h / 15 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: H2, / Raney nickel / methanol / 760 Torr 2: 0.1 g / Br2 / acetic acid / 72 h / 28 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: H2, / Raney nickel / methanol / 760 Torr 2: N,N-dimethylaniline / acetonitrile / 16 h / 28 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: H2, / Raney nickel / methanol / 760 Torr 2: 3.8 g / N,N-dimethylaniline / acetonitrile / 4 h / 28 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: H2, / Raney nickel / methanol / 760 Torr 2: CH2Cl2; acetonitrile / 16 h / 28 °C 3: lead tetraacetate / CH2Cl2 / 4 h / 15 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: H2, / Raney nickel / methanol / 760 Torr 2: CH2Cl2; acetonitrile / 16 h / 28 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: H2, / Raney nickel / methanol / 760 Torr 2: CH2Cl2; acetonitrile / 16 h / 28 °C 3: lead tetraacetate / CH2Cl2 / 4 h / 15 °C 4: sodium azide / acetic acid; H2O / 1 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: NOCl, NaOAc, P2O5 / acetic acid; acetic anhydride / 8 °C 2: benzene / 40 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | With potassium carbonate; sodium iodide In acetone at 50℃; for 6h; | IV EXAMPLE IV; N-(2-dimethylamino-ethyl)-N-methylsulphonyl-4-nitroaniline [00600] 38.9 g of N-methylsulphonyl-4-nitroaniline are dissolved in 2.0 l of acetone, 51.9 g of 1-chloro-2-dimethylamino-ethane, 77.4 g of potassium carbonate and 5.0 g of sodium iodide are added and the mixture is stirred for a total of 4 days at 50° C., while after 12 hours a further 25.9 g of 1-chloro-2dimethylamino-ethane, 49.8 g of potassium carbonate and 5.0 g of sodium iodide in 500 ml of acetone are added and after 36 hours another 26.0 g of 1-chloro-2-dimethylamino-ethane, 50.0 g of potassium carbonate and 5.0 g of sodium iodide in 100 ml of acetone are added. After this time the mixture is filtered and the filtrate evaporated down. The residue is stirred with ether, suction filtered and dried at 40° C. [00601] Yield: 25.3 g (49% of theory), Rf value: 0.5 (silica gel, methylene chloride/methanol/ammonia=9:1:0.1) C11H17N3O4S. [00602] ESI mass spectrum: m/z=288 [M+H+]. |
49% | With potassium carbonate In acetone at 50℃; for 96h; | XV EXAMPLE XV; N-(2-dimethylamino-ethyl)-N-methylsulphonyl-4-nitroaniline 38.9 g of N-methylsulphonyl-4-nitroaniline are dissolved in 2.0 l of acetone, 51.9 g of 1-chloro-2-dimethylamino-ethane, 77.4 g of potassium carbonate and 5.0 g of sodium iodide added and the mixture is stirred for a total of 4 days at 50° C., adding, after 12 hours, a further 25.9 g of 1-chloro-2-dimethylamino-ethane, 49.8 g of potassium carbonate and 5.0 g of sodium iodide in 500 ml of acetone and, after 36 hours, a further 26.0 g of 1-chloro-2-dimethylamino-ethane, 50.0 g of potassium carbonate and 5.0 g of sodium iodide in 100 ml of acetone.. After this time the mixture is filtered and the filtrate is evaporated down.. The residue is stirred with ether, suction filtered and dried at 40° C. Yield: 25.3 g (49% of theory), Rf value: 0.5 (silica gel, methylene chloride/methanol/ammonia=9:1:0.1) C11H17N3O4S ESI mass spectrum: m/z=288 [M+H+] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With potassium carbonate; sodium iodide In acetone for 21h; | |
53% | With potassium carbonate; sodium iodide In acetone at 50℃; for 72h; | |
43% | With potassium carbonate; sodium iodide In acetone at 0 - 50℃; for 20h; Inert atmosphere; | 6.4.5 6.4.5. N-(2-(dimethylamino)ethyl)-N-(4-nitrophenyl)methanesulfonamide (D8) To a stirred solution of compound D7 (800 mg, 3.70 mmol) in acetone (15 ml) were added potassium carbonate (1.32 g, 9.62 mmol), sodium iodide (110 mg, 0.74 mmol) and compound B6 (799 mg, 5.55 mmol) at 0° C. under inert atmosphere. The reaction mixture was heated to 50° C. and stirred for 20 h. After complete consumption of the starting material (monitored by TLC), the volatiles were removed in vacuo. The residue was diluted with water (20 ml) and extracted with EtOAc (2×40 ml). The combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo to obtain the crude product, which was purified by silica gel column chromatography using 5% MeOH/CH2Cl2 to afford compound D8 (460 mg, 43%) as a pale yellow solid. 1H NMR (500 MHz, DMSO-d6): δ 8.27 (d, J=9.5 Hz, 2H), 7.68 (d, J=9.5 Hz, 2H), 3.85 (t, J=6.5 Hz, 2H), 3.13 (s, 3H), 2.31 (t, J=6.5 Hz, 2H), 2.12 (s, 6H) . LC-MS (ESI): m/z 288.3 [M+H]+ |
43% | With potassium carbonate; sodium iodide In acetone at 0 - 50℃; for 20h; Inert atmosphere; | 6.4.5 6.4.5. N-(2-(dimethylamino)ethyl)-N-(4-nitrophenyl)methanesulfonamide (D8) To a stirred solution of compound D7 (800 mg, 3.70 mmol) in acetone (15 ml) were added potassium carbonate (1.32 g, 9.62 mmol), sodium iodide (110 mg, 0.74 mmol) and compound B6 (799 mg, 5.55 mmol) at 0 °C under inert atmosphere. The reaction mixture was heated to 50 °C and stirred for 20 h. After complete consumption of the starting material (monitored by TLC), the volatiles were removed in vacuo. The residue was diluted with water (20 ml) and extracted with EtOAc (2 x 40 ml). The combined organic extracts were dried over Na2SC>4, filtered and concentrated in vacuo to obtain the crude product, which was purified by silica gel column chromatography using 5% MeOH/CH2CI2to afford compound D8 (460 mg, 43%) as a pale yellow solid.1H NMR (500 MHz, DMSO -de)6 8.27 (d, J = 9.5 Hz, 2H), 7.68 (d, J = 9.5 Hz, 2H), 3.85 (t, J = 6.5 Hz, 2H), 3.13 (s, 3H), 2.31 (t, J = 6.5 Hz, 2H), 2.12 (s, 6H)LC-MS (ESI):m/z 288.3 [M + H]+ |
43% | With potassium carbonate; sodium iodide In acetone at 0 - 50℃; for 20h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol; (2S)-N-methyl-1-phenylpropan-2-amine hydrate; dimethyl sulfoxide | VII 4-(N-methyl-N-methylsulphonyl-amino)-phenylamine EXAMPLE VII 4-(N-methyl-N-methylsulphonyl-amino)-phenylamine 4.3 g of 4-(N-methylsulphonylamino)-nitrobenzene are dissolved in 40 ml of DMSO and stirred with 2,5 g of potassium-tert-butoxide for 1 hour at RT. 4.2 g of methyl iodide in 10 ml of DMSO are added dropwise to the solution and stirred overnight at ambient temperature. The mixture is then poured onto about 120 ml of ice water and extracted with ethyl acetate. The organic phase is washed with water three times, then dried over sodium sulphate and concentrated by evaporation. The residue is triturated with diethylether, suction filtered and dried. Yield: 4.6 g Melting point 105-106° C. Rf value 0.52 (silica gel, toluene: ethyl acetate=7:3) 4.1 g of 4-(N-methyl-N-methylsulphonyl-amino)-nitrobenzene are taken up in 80 ml of methanol, combined with 1 g of palladium charcoal and hydrogenated at ambient temperature under 5 bar. After 30 minutes the catalyst is filtered off, the mixture is evaporated down and the remaining product is triturated with diethylether. Yield: 3.6 g Melting point 116° C. Rf value 0.14 (silica gel, toluene: ethyl acetate=7:3) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | Stage #1: 4-nitro-aniline; Methanesulfonic anhydride With triethylamine In dichloromethane at 20℃; Stage #2: With sodium hydroxide In methanol; water at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | Stage #1: N-(4-nitrophenyl)methanesulfonamide With potassium <i>tert</i>-butylate In dimethyl sulfoxide at 20℃; for 1h; Stage #2: methyl iodide In dimethyl sulfoxide at 20℃; for 8h; | |
With potassium carbonate In acetonitrile at 20℃; for 18h; | Intermediate compound 10: N-methyl-N-(4-nitrophenyl)-methanesulfonamide To a solution of intermediate compound 8 (2.31 mmol, 0.50 g) in anhydrous ACN (15 ml_), anhydrous potassium carbonate (5.78 mmol, 0.79 g) and iodomethane (7.39 mmol, 0.46 ml_) were added sequentially and the reaction mixture was stirred at room temperature for 18 h. The solvent was concentrated under vacuum and the crude residue was treated with water and EtAOc. The organic phase was separated and washed with saturated aqueous sodium carbonate solution and brine, dried over anhydrous magnesium sulfate, filtered and concentrated under vacuum to give the title compound which was used in the next step without further purification. (0.50 g. Yield=95%) 1 H NMR (400 MHz, CDCI3) δ 8.26 (2H, d, J = 9.2 Hz), 7.56 (2H, d, J = 9.2 Hz), 3.42 (3H, s), 2.92 (3H, s). LC-MS: tR =2.43 [M+H]+= 231 (method 3) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | Stage #1: N-(4-nitrophenyl)methanesulfonamide With potassium <i>tert</i>-butylate In dimethyl sulfoxide at 20℃; for 1h; Stage #2: ethyl bromoacetate In dimethyl sulfoxide at 20℃; for 18h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With trifluoroacetic acid for 10h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: palladium 10% on activated carbon; ammonium formate / methanol / 45 °C / Inert atmosphere; Cooling with ice 2: toluene-4-sulfonic acid / ethanol / Reflux |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: palladium 10% on activated carbon; ammonium formate / methanol / 45 °C / Inert atmosphere; Cooling with ice 2: toluene-4-sulfonic acid / ethanol / Reflux 3: copper(l) iodide; potassium carbonate; <i>L</i>-proline / dimethyl sulfoxide / 2 h / 150 °C / Microwave irradiation |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: palladium 10% on activated carbon; ammonium formate / methanol / 45 °C / Inert atmosphere; Cooling with ice 2: toluene-4-sulfonic acid / ethanol / Reflux |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: palladium 10% on activated carbon; ammonium formate / methanol / 45 °C / Inert atmosphere; Cooling with ice 2: toluene-4-sulfonic acid / ethanol / Reflux 3: copper(l) iodide; potassium carbonate; <i>L</i>-proline / dimethyl sulfoxide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: palladium 10% on activated carbon; ammonium formate / methanol / 45 °C / Inert atmosphere; Cooling with ice 2: toluene-4-sulfonic acid / ethanol / Reflux 3: copper(l) iodide; potassium carbonate; <i>L</i>-proline / dimethyl sulfoxide / 2 h / 150 °C / Microwave irradiation 4: lithium hydroxide monohydrate / tetrahydrofuran; water / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: palladium 10% on activated carbon; ammonium formate / methanol / 45 °C / Inert atmosphere; Cooling with ice 2: toluene-4-sulfonic acid / ethanol / Reflux 3: copper(l) iodide; potassium carbonate; <i>L</i>-proline / dimethyl sulfoxide 4: water; lithium hydroxide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: hydrogen; palladium 10% on activated carbon 2: aluminum (III) chloride / -40 °C 3: sulfuric acid / 2.5 h / 130 °C | ||
Multi-step reaction with 4 steps 1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4: sulfuric acid / water / 2.5 h / 130 °C | ||
Multi-step reaction with 4 steps 1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4: hydrogenchloride / water / 16 h / 105 °C |
Multi-step reaction with 5 steps 1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4: sulfuric acid / water / 2.5 h / 130 °C 5: pyridine / acetonitrile / 15.25 h / 25 °C | ||
Multi-step reaction with 3 steps 1.1: hydrogen / palladium 10% on activated carbon / methanol; ethyl acetate; N,N-dimethyl-formamide / 4.5 h / 25 °C 2.1: Nitroethane / 0.25 h / -40 °C 2.2: 0.5 h / 110 °C 3.1: hydrogenchloride / water / 16 h / 105 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: hydrogen; palladium 10% on activated carbon 2: aluminum (III) chloride / -40 °C | ||
Multi-step reaction with 3 steps 1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C | ||
Multi-step reaction with 2 steps 1.1: hydrogen / palladium 10% on activated carbon / methanol; ethyl acetate; N,N-dimethyl-formamide / 4.5 h / 25 °C 2.1: Nitroethane / 0.25 h / -40 °C 2.2: 0.5 h / 110 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: potassium carbonate / acetonitrile / 18 h / 20 °C 2: tin(II) chloride dihdyrate / tetrahydrofuran / 16 h / 70 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With palladium diacetate; caesium carbonate; triphenylphosphine In 1,4-dioxane at 110℃; for 16h; Inert atmosphere; Sealed tube; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 3h; | 6.1.3. ({4-[(Benzenesulfonyl-{4-[(benzylmethanesulfonylamino)methyl]phenyl}amino)methyl]phenyl}methanesulfonylamino)acetic acid methyl ester (P5) General procedure: To a stirred solution of 8 (500 mg, 2.17 mmol) in DMF (12 mL)at ambient temperature was added benzyl bromide (0.31 mL,2.61 mmol) and potassium carbonate (600 mg, 4.34 mmol) at roomtemperature. After 3 h, the reaction mixture was filtrated andwashed with ethyl acetate (140 mL). The filtrate was washed withsaturated brine and dried over anhydrous Na2SO4 and the organicphase was concentrated under vacuum to afford the yellow solid.Then the resulting solid was recrystallized from ethanol and thepale yellow crystals 9a were removed by filtration (523 mg, 75%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: potassium carbonate / N,N-dimethyl-formamide / 3 h / 20 °C 2: sodium tetrahydroborate; nickel(II) chloride hexahydrate / methanol / 0.5 h / 0 - 20 °C 3: dmap; pyridine / dichloromethane / 24 h / 20 °C / Inert atmosphere 4: potassium carbonate; potassium iodide / N,N-dimethyl-formamide / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: potassium carbonate / N,N-dimethyl-formamide / 3 h / 20 °C 2: sodium tetrahydroborate; nickel(II) chloride hexahydrate / methanol / 0.5 h / 0 - 20 °C 3: dmap; pyridine / N,N-dimethyl-formamide / 24 h / 20 °C / Inert atmosphere 4: potassium carbonate; potassium iodide / N,N-dimethyl-formamide / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 3 h / 20 °C 2: sodium tetrahydroborate; nickel(II) chloride hexahydrate / methanol / 0.5 h / 0 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 3 h / 20 °C 2: sodium tetrahydroborate; nickel(II) chloride hexahydrate / methanol / 0.5 h / 0 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: potassium carbonate / N,N-dimethyl-formamide / 3 h / 20 °C 2: sodium tetrahydroborate; nickel(II) chloride hexahydrate / methanol / 0.5 h / 0 - 20 °C 3: dmap; pyridine / dichloromethane / 24 h / 20 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: potassium carbonate / N,N-dimethyl-formamide / 3 h / 20 °C 2: sodium tetrahydroborate; nickel(II) chloride hexahydrate / methanol / 0.5 h / 0 - 20 °C 3: dmap; pyridine / N,N-dimethyl-formamide / 24 h / 20 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75.3% | With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 3h; | 6.1.3. ({4-[(Benzenesulfonyl-{4-[(benzylmethanesulfonylamino)methyl]phenyl}amino)methyl]phenyl}methanesulfonylamino)acetic acid methyl ester (P5) General procedure: To a stirred solution of 8 (500 mg, 2.17 mmol) in DMF (12 mL)at ambient temperature was added benzyl bromide (0.31 mL,2.61 mmol) and potassium carbonate (600 mg, 4.34 mmol) at roomtemperature. After 3 h, the reaction mixture was filtrated andwashed with ethyl acetate (140 mL). The filtrate was washed withsaturated brine and dried over anhydrous Na2SO4 and the organicphase was concentrated under vacuum to afford the yellow solid.Then the resulting solid was recrystallized from ethanol and thepale yellow crystals 9a were removed by filtration (523 mg, 75%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: iron; ammonium chloride / ethanol; water / 1 h / 90 °C 2: triethylamine / water / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
33% | With iodobenzene; 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 6h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4: sulfuric acid / water / 2.5 h / 130 °C 5: pyridine / 3 h / 120 °C 6: 1,8-diazabicyclo[5.4.0]undec-7-ene / pyridine / 16 h / 120 °C | ||
Multi-step reaction with 6 steps 1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4: hydrogenchloride / water / 16 h / 105 °C 5: pyridine / 3 h / 120 °C 6: 1,8-diazabicyclo[5.4.0]undec-7-ene / pyridine / 16 h / 120 °C | ||
Multi-step reaction with 7 steps 1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4: sulfuric acid / water / 2.5 h / 130 °C 5: pyridine / acetonitrile / 15.25 h / 25 °C 6: pyridine / 3 h / 120 °C 7: 1,8-diazabicyclo[5.4.0]undec-7-ene / pyridine / 16 h / 120 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4: sulfuric acid / water / 2.5 h / 130 °C 5: pyridine / 3 h / 120 °C 6: 1,8-diazabicyclo[5.4.0]undec-7-ene / pyridine / 16 h / 120 °C | ||
Multi-step reaction with 6 steps 1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4: hydrogenchloride / water / 16 h / 105 °C 5: pyridine / 3 h / 120 °C 6: 1,8-diazabicyclo[5.4.0]undec-7-ene / pyridine / 16 h / 120 °C | ||
Multi-step reaction with 7 steps 1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4: sulfuric acid / water / 2.5 h / 130 °C 5: pyridine / acetonitrile / 15.25 h / 25 °C 6: pyridine / 3 h / 120 °C 7: 1,8-diazabicyclo[5.4.0]undec-7-ene / pyridine / 16 h / 120 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1.1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2.1: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3.1: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4.1: sulfuric acid / water / 2.5 h / 130 °C 5.1: 1 h / 160 °C 6.1: sodium hydroxide / water / 1.5 h / 100 °C 6.2: 0 °C / pH 1 - 2 7.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 12 h / 25 °C 8.1: sodium ethanolate / ethanol / 12 h / 60 °C | ||
Multi-step reaction with 8 steps 1.1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2.1: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3.1: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4.1: hydrogenchloride / water / 16 h / 105 °C 5.1: 1 h / 160 °C 6.1: sodium hydroxide / water / 1.5 h / 100 °C 6.2: 0 °C / pH 1 - 2 7.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 12 h / 25 °C 8.1: sodium ethanolate / ethanol / 12 h / 60 °C | ||
Multi-step reaction with 8 steps 1.1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2.1: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3.1: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4.1: sulfuric acid / water / 2.5 h / 130 °C 5.1: N,N-dimethyl acetamide / 1 h / 0 - 25 °C 6.1: sodium hydroxide / water / 1 h / 25 - 100 °C 6.2: 21.17 h / 0 - 25 °C 7.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 12 h / 25 °C 8.1: sodium ethanolate / ethanol / 12 h / 60 °C |
Multi-step reaction with 8 steps 1.1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2.1: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3.1: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4.1: hydrogenchloride / water / 16 h / 105 °C 5.1: N,N-dimethyl acetamide / 1 h / 0 - 25 °C 6.1: sodium hydroxide / water / 1 h / 25 - 100 °C 6.2: 21.17 h / 0 - 25 °C 7.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 12 h / 25 °C 8.1: sodium ethanolate / ethanol / 12 h / 60 °C | ||
Multi-step reaction with 8 steps 1.1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2.1: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3.1: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4.1: sulfuric acid / water / 2.5 h / 130 °C 5.1: diethyl ether; N,N-dimethyl acetamide / 1 h / 25 °C 6.1: sodium hydroxide / water / 1.5 h / 100 °C 6.2: 0 °C / pH 1 - 2 7.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 12 h / 25 °C 8.1: sodium ethanolate / ethanol / 12 h / 60 °C | ||
Multi-step reaction with 8 steps 1.1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2.1: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3.1: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4.1: hydrogenchloride / water / 16 h / 105 °C 5.1: diethyl ether; N,N-dimethyl acetamide / 1 h / 25 °C 6.1: sodium hydroxide / water / 1.5 h / 100 °C 6.2: 0 °C / pH 1 - 2 7.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 12 h / 25 °C 8.1: sodium ethanolate / ethanol / 12 h / 60 °C | ||
Multi-step reaction with 9 steps 1.1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2.1: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3.1: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4.1: sulfuric acid / water / 2.5 h / 130 °C 5.1: pyridine / acetonitrile / 15.25 h / 25 °C 6.1: 1 h / 160 °C 7.1: sodium hydroxide / water / 1.5 h / 100 °C 7.2: 0 °C / pH 1 - 2 8.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 12 h / 25 °C 9.1: sodium ethanolate / ethanol / 12 h / 60 °C | ||
Multi-step reaction with 9 steps 1.1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2.1: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3.1: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4.1: sulfuric acid / water / 2.5 h / 130 °C 5.1: pyridine / acetonitrile / 15.25 h / 25 °C 6.1: N,N-dimethyl acetamide / 1 h / 0 - 25 °C 7.1: sodium hydroxide / water / 1 h / 25 - 100 °C 7.2: 21.17 h / 0 - 25 °C 8.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 12 h / 25 °C 9.1: sodium ethanolate / ethanol / 12 h / 60 °C | ||
Multi-step reaction with 9 steps 1.1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2.1: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3.1: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4.1: sulfuric acid / water / 2.5 h / 130 °C 5.1: pyridine / acetonitrile / 15.25 h / 25 °C 6.1: diethyl ether; N,N-dimethyl acetamide / 1 h / 25 °C 7.1: sodium hydroxide / water / 1.5 h / 100 °C 7.2: 0 °C / pH 1 - 2 8.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 12 h / 25 °C 9.1: sodium ethanolate / ethanol / 12 h / 60 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2: Nitroethane / 0.25 - 2 h / -40 - -20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1.1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2.1: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3.1: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4.1: sulfuric acid / water / 2.5 h / 130 °C 5.1: diethyl ether; N,N-dimethyl acetamide / 1 h / 25 °C 6.1: sodium hydroxide / water / 1.5 h / 100 °C 6.2: 0 °C / pH 1 - 2 | ||
Multi-step reaction with 6 steps 1.1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2.1: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3.1: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4.1: hydrogenchloride / water / 16 h / 105 °C 5.1: diethyl ether; N,N-dimethyl acetamide / 1 h / 25 °C 6.1: sodium hydroxide / water / 1.5 h / 100 °C 6.2: 0 °C / pH 1 - 2 | ||
Multi-step reaction with 6 steps 1.1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2.1: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3.1: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4.1: sulfuric acid / water / 2.5 h / 130 °C 5.1: 1 h / 160 °C 6.1: sodium hydroxide / water / 1.5 h / 100 °C 6.2: 0 °C / pH 1 - 2 |
Multi-step reaction with 6 steps 1.1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2.1: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3.1: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4.1: hydrogenchloride / water / 16 h / 105 °C 5.1: 1 h / 160 °C 6.1: sodium hydroxide / water / 1.5 h / 100 °C 6.2: 0 °C / pH 1 - 2 | ||
Multi-step reaction with 6 steps 1.1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2.1: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3.1: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4.1: sulfuric acid / water / 2.5 h / 130 °C 5.1: N,N-dimethyl acetamide / 1 h / 0 - 25 °C 6.1: sodium hydroxide / water / 1 h / 25 - 100 °C 6.2: 21.17 h / 0 - 25 °C | ||
Multi-step reaction with 6 steps 1.1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2.1: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3.1: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4.1: hydrogenchloride / water / 16 h / 105 °C 5.1: N,N-dimethyl acetamide / 1 h / 0 - 25 °C 6.1: sodium hydroxide / water / 1 h / 25 - 100 °C 6.2: 21.17 h / 0 - 25 °C | ||
Multi-step reaction with 7 steps 1.1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2.1: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3.1: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4.1: sulfuric acid / water / 2.5 h / 130 °C 5.1: pyridine / acetonitrile / 15.25 h / 25 °C 6.1: N,N-dimethyl acetamide / 1 h / 0 - 25 °C 7.1: sodium hydroxide / water / 1 h / 25 - 100 °C 7.2: 21.17 h / 0 - 25 °C | ||
Multi-step reaction with 7 steps 1.1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2.1: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3.1: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4.1: sulfuric acid / water / 2.5 h / 130 °C 5.1: pyridine / acetonitrile / 15.25 h / 25 °C 6.1: diethyl ether; N,N-dimethyl acetamide / 1 h / 25 °C 7.1: sodium hydroxide / water / 1.5 h / 100 °C 7.2: 0 °C / pH 1 - 2 | ||
Multi-step reaction with 7 steps 1.1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2.1: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3.1: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4.1: sulfuric acid / water / 2.5 h / 130 °C 5.1: pyridine / acetonitrile / 15.25 h / 25 °C 6.1: 1 h / 160 °C 7.1: sodium hydroxide / water / 1.5 h / 100 °C 7.2: 0 °C / pH 1 - 2 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4: sulfuric acid / water / 2.5 h / 130 °C 5: N,N-dimethyl acetamide / 1 h / 0 - 25 °C | ||
Multi-step reaction with 5 steps 1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4: hydrogenchloride / water / 16 h / 105 °C 5: N,N-dimethyl acetamide / 1 h / 0 - 25 °C | ||
Multi-step reaction with 6 steps 1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4: sulfuric acid / water / 2.5 h / 130 °C 5: pyridine / acetonitrile / 15.25 h / 25 °C 6: N,N-dimethyl acetamide / 1 h / 0 - 25 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4: sulfuric acid / water / 2.5 h / 130 °C 5: 1 h / 160 °C | ||
Multi-step reaction with 5 steps 1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4: hydrogenchloride / water / 16 h / 105 °C 5: 1 h / 160 °C | ||
Multi-step reaction with 5 steps 1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4: sulfuric acid / water / 2.5 h / 130 °C 5: diethyl ether; N,N-dimethyl acetamide / 1 h / 25 °C |
Multi-step reaction with 5 steps 1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4: hydrogenchloride / water / 16 h / 105 °C 5: diethyl ether; N,N-dimethyl acetamide / 1 h / 25 °C | ||
Multi-step reaction with 6 steps 1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4: sulfuric acid / water / 2.5 h / 130 °C 5: pyridine / acetonitrile / 15.25 h / 25 °C 6: diethyl ether; N,N-dimethyl acetamide / 1 h / 25 °C | ||
Multi-step reaction with 6 steps 1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4: sulfuric acid / water / 2.5 h / 130 °C 5: pyridine / acetonitrile / 15.25 h / 25 °C 6: 1 h / 160 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4: sulfuric acid / water / 2.5 h / 130 °C 5: pyridine / 3 h / 120 °C | ||
Multi-step reaction with 5 steps 1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4: hydrogenchloride / water / 16 h / 105 °C 5: pyridine / 3 h / 120 °C | ||
Multi-step reaction with 6 steps 1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4: sulfuric acid / water / 2.5 h / 130 °C 5: pyridine / acetonitrile / 15.25 h / 25 °C 6: pyridine / 3 h / 120 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4: sulfuric acid / water / 2.5 h / 130 °C 5: pyridine / 3 h / 120 °C | ||
Multi-step reaction with 5 steps 1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4: hydrogenchloride / water / 16 h / 105 °C 5: pyridine / 3 h / 120 °C | ||
Multi-step reaction with 6 steps 1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4: sulfuric acid / water / 2.5 h / 130 °C 5: pyridine / acetonitrile / 15.25 h / 25 °C 6: pyridine / 3 h / 120 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 7 steps 1.1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2.1: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3.1: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4.1: sulfuric acid / water / 2.5 h / 130 °C 5.1: N,N-dimethyl acetamide / 1 h / 0 - 25 °C 6.1: sodium hydroxide / water / 1 h / 25 - 100 °C 6.2: 21.17 h / 0 - 25 °C 7.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 12 h / 25 °C | ||
Multi-step reaction with 7 steps 1.1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2.1: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3.1: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4.1: hydrogenchloride / water / 16 h / 105 °C 5.1: N,N-dimethyl acetamide / 1 h / 0 - 25 °C 6.1: sodium hydroxide / water / 1 h / 25 - 100 °C 6.2: 21.17 h / 0 - 25 °C 7.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 12 h / 25 °C | ||
Multi-step reaction with 7 steps 1.1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2.1: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3.1: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4.1: sulfuric acid / water / 2.5 h / 130 °C 5.1: diethyl ether; N,N-dimethyl acetamide / 1 h / 25 °C 6.1: sodium hydroxide / water / 1.5 h / 100 °C 6.2: 0 °C / pH 1 - 2 7.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 12 h / 25 °C |
Multi-step reaction with 7 steps 1.1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2.1: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3.1: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4.1: hydrogenchloride / water / 16 h / 105 °C 5.1: diethyl ether; N,N-dimethyl acetamide / 1 h / 25 °C 6.1: sodium hydroxide / water / 1.5 h / 100 °C 6.2: 0 °C / pH 1 - 2 7.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 12 h / 25 °C | ||
Multi-step reaction with 7 steps 1.1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2.1: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3.1: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4.1: sulfuric acid / water / 2.5 h / 130 °C 5.1: 1 h / 160 °C 6.1: sodium hydroxide / water / 1.5 h / 100 °C 6.2: 0 °C / pH 1 - 2 7.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 12 h / 25 °C | ||
Multi-step reaction with 7 steps 1.1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2.1: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3.1: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4.1: hydrogenchloride / water / 16 h / 105 °C 5.1: 1 h / 160 °C 6.1: sodium hydroxide / water / 1.5 h / 100 °C 6.2: 0 °C / pH 1 - 2 7.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 12 h / 25 °C | ||
Multi-step reaction with 8 steps 1.1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2.1: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3.1: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4.1: sulfuric acid / water / 2.5 h / 130 °C 5.1: pyridine / acetonitrile / 15.25 h / 25 °C 6.1: 1 h / 160 °C 7.1: sodium hydroxide / water / 1.5 h / 100 °C 7.2: 0 °C / pH 1 - 2 8.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 12 h / 25 °C | ||
Multi-step reaction with 8 steps 1.1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2.1: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3.1: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4.1: sulfuric acid / water / 2.5 h / 130 °C 5.1: pyridine / acetonitrile / 15.25 h / 25 °C 6.1: N,N-dimethyl acetamide / 1 h / 0 - 25 °C 7.1: sodium hydroxide / water / 1 h / 25 - 100 °C 7.2: 21.17 h / 0 - 25 °C 8.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 12 h / 25 °C | ||
Multi-step reaction with 8 steps 1.1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2.1: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3.1: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4.1: sulfuric acid / water / 2.5 h / 130 °C 5.1: pyridine / acetonitrile / 15.25 h / 25 °C 6.1: diethyl ether; N,N-dimethyl acetamide / 1 h / 25 °C 7.1: sodium hydroxide / water / 1.5 h / 100 °C 7.2: 0 °C / pH 1 - 2 8.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 12 h / 25 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: hydrogen / 5%-palladium/activated carbon / tetrahydrofuran / 96 h / 25 °C / 760.05 Torr 2: Nitroethane / 0.25 - 2 h / -40 - -20 °C 3: aluminum (III) chloride / Nitroethane / 0.5 - 0.83 h / 25 - 110 °C 4: sulfuric acid / water / 2.5 h / 130 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: hydrogen / palladium 10% on activated carbon / methanol; ethyl acetate; N,N-dimethyl-formamide / 4.5 h / 25 °C 2.1: Nitroethane / 0.25 h / -40 °C 2.2: 0.5 h / 110 °C 3.1: hydrogenchloride / water / 16 h / 105 °C 4.1: pyridine / 2 h / 110 °C 4.2: 4.5 h / 110 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With potassium carbonate; potassium iodide In acetone at 80℃; for 2h; Microwave irradiation; | 31C Step C: N-(4-nitrophenyl)-N-(2-(3,4-dihydroisoquinolin-2(1H)-yl)-2-oxoethyl)methanesulfonamide 2-bromo-1-(3,4-dihydroisoquinolin-2(1H)yl)ethanone (200 mg) and N-(4-nitrophenyl)methanesulfonamide (170 mg, 1 equiv) dissolved In 15 ml of acetone, potassium carbonate (119 mg, 1.1 equiv), KI (144 mg 1.1 equiv) was then added. After reacting at 80 ° C for 2 hours under microwave conditions, the solution after cooling was cooled, acetone was spun off, and ethyl acetate was added.(20 ml) was diluted, then water was added, and extraction was performed with ethyl acetate. The extracted ethyl acetate layer was washed with brine, dried over anhydrous sodium sulfate, and then the solvent was removed by evaporation, using a petroleum ether/ethyl acetate (2:1) solvent. The product N-(4-nitrophenyl)-N-(2-(3,4-dihydroisoquinolin-2(1H)-yl)-2-oxoethyl)methanesulfonamide (150 mg, 50%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: tin(II) chloride dihdyrate / ethanol / 16 h / Reflux 2: diphenylsilane; 3-Methyl-1-phenyl-2-phospholene 1-oxide / toluene / 24 h / 110 °C / Sealed tube |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | With potassium carbonate; sodium iodide; In acetone; at 0 - 50℃; for 20h;Inert atmosphere; | To a stirred solution of compound D7 (800 mg, 3.70 mmol) in acetone (15 ml) were added potassium carbonate (1.32 g, 9.62 mmol), sodium iodide (110 mg, 0.74 mmol) and compound B6 (799 mg, 5.55 mmol) at 0 C under inert atmosphere. The reaction mixture was heated to 50 C and stirred for 20 h. After complete consumption of the starting material (monitored by TLC), the volatiles were removed in vacuo. The residue was diluted with water (20 ml) and extracted with EtOAc (2 x 40 ml). The combined organic extracts were dried over Na2SC>4, filtered and concentrated in vacuo to obtain the crude product, which was purified by silica gel column chromatography using 5% MeOH/CH2Cl2 to afford compound D8 (460 mg, 43%) as a pale yellow solid.1H NMR (500 MHz, DMSO -de)6 8.27 (d, J = 9.5 Hz, 2H), 7.68 (d, J = 9.5 Hz, 2H), 3.85 (t, J = 6.5 Hz, 2H), 3.13 (s, 3H), 2.31 (t, J = 6.5 Hz, 2H), 2.12 (s, 6H) LC-MS (ESI):m/z 288.3 [M + H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: potassium carbonate; sodium iodide / acetone / 20 h / 0 - 50 °C / Inert atmosphere 2: palladium 10% on activated carbon; hydrogen / methanol / 3 h / 21 °C | ||
Multi-step reaction with 2 steps 1: potassium carbonate; sodium iodide / acetone / 20 h / 0 - 50 °C / Inert atmosphere 2: palladium 10% on activated carbon; hydrogen / methanol / 3 h / 21 °C | ||
Multi-step reaction with 2 steps 1: potassium carbonate; sodium iodide / acetone / 20 h / 0 - 50 °C / Inert atmosphere 2: palladium 10% on activated carbon; hydrogen / methanol / 3 h / 21 °C |
Multi-step reaction with 2 steps 1: potassium carbonate; sodium iodide / acetone / 20 h / 0 - 50 °C / Inert atmosphere 2: palladium 10% on activated carbon; hydrogen / methanol / 3 h / 21 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: potassium carbonate; sodium iodide / acetone / 20 h / 0 - 50 °C / Inert atmosphere 2: palladium 10% on activated carbon; hydrogen / methanol / 3 h / 21 °C 3: 1-(Trimethylsilyl)imidazole / tetrahydrofuran / 1 h / 170 °C / Microwave irradiation | ||
Multi-step reaction with 3 steps 1: potassium carbonate; sodium iodide / acetone / 20 h / 0 - 50 °C / Inert atmosphere 2: palladium 10% on activated carbon; hydrogen / methanol / 3 h / 21 °C 3: 1-(Trimethylsilyl)imidazole / tetrahydrofuran / 1 h / 170 °C / Microwave irradiation | ||
Multi-step reaction with 3 steps 1: potassium carbonate; sodium iodide / acetone / 20 h / 0 - 50 °C / Inert atmosphere 2: palladium 10% on activated carbon; hydrogen / methanol / 3 h / 21 °C 3: 1-(Trimethylsilyl)imidazole / 1 h / 170 °C / Microwave irradiation |
Multi-step reaction with 3 steps 1: potassium carbonate; sodium iodide / acetone / 20 h / 0 - 50 °C / Inert atmosphere 2: palladium 10% on activated carbon; hydrogen / methanol / 3 h / 21 °C 3: 1-(Trimethylsilyl)imidazole / tetrahydrofuran / 1 h / 170 °C / Microwave irradiation |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: potassium carbonate; sodium iodide / acetone / 20 h / 0 - 50 °C / Inert atmosphere 2.1: palladium 10% on activated carbon; hydrogen / methanol / 3 h / 21 °C 3.1: 1-(Trimethylsilyl)imidazole / tetrahydrofuran / 1 h / 170 °C / Microwave irradiation 4.1: 2,2,2-Trichloroethyl chloroformate / toluene / 16 h / 21 - 120 °C / Inert atmosphere; Reflux 4.2: 8 h / 21 - 50 °C / Inert atmosphere | ||
Multi-step reaction with 4 steps 1.1: potassium carbonate; sodium iodide / acetone / 20 h / 0 - 50 °C / Inert atmosphere 2.1: palladium 10% on activated carbon; hydrogen / methanol / 3 h / 21 °C 3.1: 1-(Trimethylsilyl)imidazole / tetrahydrofuran / 1 h / 170 °C / Microwave irradiation 4.1: 2,2,2-Trichloroethyl chloroformate / toluene / 16 h / 120 °C / Inert atmosphere 4.2: 8 h / 50 °C / Inert atmosphere | ||
Multi-step reaction with 4 steps 1.1: potassium carbonate; sodium iodide / acetone / 20 h / 0 - 50 °C / Inert atmosphere 2.1: palladium 10% on activated carbon; hydrogen / methanol / 3 h / 21 °C 3.1: 1-(Trimethylsilyl)imidazole / 1 h / 170 °C / Microwave irradiation 4.1: 2,2,2-Trichloroethyl chloroformate / toluene / 16 h / 120 °C / Inert atmosphere 4.2: 8 h / 21 - 50 °C / Inert atmosphere |
Multi-step reaction with 4 steps 1.1: potassium carbonate; sodium iodide / acetone / 20 h / 0 - 50 °C / Inert atmosphere 2.1: palladium 10% on activated carbon; hydrogen / methanol / 3 h / 21 °C 3.1: 1-(Trimethylsilyl)imidazole / tetrahydrofuran / 1 h / 170 °C / Microwave irradiation 4.1: 2,2,2-Trichloroethyl chloroformate / toluene / 16 h / 21 - 120 °C / Inert atmosphere 4.2: 8 h / 21 - 50 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 0 - 21 °C / Inert atmosphere 1.2: 24 h / 21 - 90 °C / Inert atmosphere 2.1: triethylamine / tetrahydrofuran / 16 h / 21 - 80 °C / Sealed tube; Inert atmosphere | ||
Multi-step reaction with 2 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 0 - 21 °C / Inert atmosphere 1.2: 24 h / 90 °C 2.1: triethylamine / tetrahydrofuran / 16 h / 80 °C / Sealed tube; Inert atmosphere | ||
Multi-step reaction with 2 steps 1.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 0 - 21 °C / Inert atmosphere 1.2: 24 h / 90 °C / Inert atmosphere 2.1: triethylamine / tetrahydrofuran / 16 h / 80 °C / Sealed tube; Inert atmosphere |
Multi-step reaction with 2 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 0 - 21 °C / Inert atmosphere 1.2: 24 h / 21 - 90 °C 2.1: triethylamine / tetrahydrofuran / 16 h / 21 - 80 °C / Sealed tube; Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 0 - 21 °C / Inert atmosphere 1.2: 24 h / 21 - 90 °C / Inert atmosphere 2.1: triethylamine / tetrahydrofuran / 16 h / 21 - 80 °C / Sealed tube; Inert atmosphere 3.1: triethylamine / dichloromethane / 5 h / 21 °C / Inert atmosphere | ||
Multi-step reaction with 3 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 0 - 21 °C / Inert atmosphere 1.2: 24 h / 90 °C 2.1: triethylamine / tetrahydrofuran / 16 h / 80 °C / Sealed tube; Inert atmosphere 3.1: triethylamine / dichloromethane / 5 h / 21 °C / Inert atmosphere | ||
Multi-step reaction with 3 steps 1.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 0 - 21 °C / Inert atmosphere 1.2: 24 h / 90 °C / Inert atmosphere 2.1: triethylamine / tetrahydrofuran / 16 h / 80 °C / Sealed tube; Inert atmosphere 3.1: triethylamine / dichloromethane / 5 h / 21 °C |
Multi-step reaction with 3 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 0 - 21 °C / Inert atmosphere 1.2: 24 h / 21 - 90 °C 2.1: triethylamine / tetrahydrofuran / 16 h / 21 - 80 °C / Sealed tube; Inert atmosphere 3.1: triethylamine / dichloromethane / 5 h / 21 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 0 - 21 °C / Inert atmosphere 1.2: 24 h / 21 - 90 °C / Inert atmosphere 2.1: triethylamine / tetrahydrofuran / 16 h / 21 - 80 °C / Sealed tube; Inert atmosphere 3.1: triethylamine / dichloromethane / 5 h / 21 °C / Inert atmosphere 4.1: hydrogen / ethanol / 1 h / 21 °C | ||
Multi-step reaction with 4 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 0 - 21 °C / Inert atmosphere 1.2: 24 h / 90 °C 2.1: triethylamine / tetrahydrofuran / 16 h / 80 °C / Sealed tube; Inert atmosphere 3.1: triethylamine / dichloromethane / 5 h / 21 °C / Inert atmosphere 4.1: hydrogen / ethanol / 1 h / 21 °C | ||
Multi-step reaction with 4 steps 1.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 0 - 21 °C / Inert atmosphere 1.2: 24 h / 90 °C / Inert atmosphere 2.1: triethylamine / tetrahydrofuran / 16 h / 80 °C / Sealed tube; Inert atmosphere 3.1: triethylamine / dichloromethane / 5 h / 21 °C 4.1: hydrogen / ethanol / 1 h / 21 °C |
Multi-step reaction with 4 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 0 - 21 °C / Inert atmosphere 1.2: 24 h / 21 - 90 °C 2.1: triethylamine / tetrahydrofuran / 16 h / 21 - 80 °C / Sealed tube; Inert atmosphere 3.1: triethylamine / dichloromethane / 5 h / 21 °C / Inert atmosphere 4.1: hydrogen / ethanol / 1 h / 21 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 0 - 21 °C / Inert atmosphere 1.2: 24 h / 21 - 90 °C / Inert atmosphere 2.1: triethylamine / tetrahydrofuran / 16 h / 21 - 80 °C / Sealed tube; Inert atmosphere 3.1: triethylamine / dichloromethane / 5 h / 21 °C / Inert atmosphere 4.1: hydrogen / ethanol / 1 h / 21 °C 5.1: 1-(Trimethylsilyl)imidazole / tetrahydrofuran / 170 °C / Microwave irradiation | ||
Multi-step reaction with 5 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 0 - 21 °C / Inert atmosphere 1.2: 24 h / 90 °C 2.1: triethylamine / tetrahydrofuran / 16 h / 80 °C / Sealed tube; Inert atmosphere 3.1: triethylamine / dichloromethane / 5 h / 21 °C / Inert atmosphere 4.1: hydrogen / ethanol / 1 h / 21 °C 5.1: 1-(Trimethylsilyl)imidazole / tetrahydrofuran / 2 h / 170 °C / Microwave irradiation | ||
Multi-step reaction with 5 steps 1.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 0 - 21 °C / Inert atmosphere 1.2: 24 h / 90 °C / Inert atmosphere 2.1: triethylamine / tetrahydrofuran / 16 h / 80 °C / Sealed tube; Inert atmosphere 3.1: triethylamine / dichloromethane / 5 h / 21 °C 4.1: hydrogen / ethanol / 1 h / 21 °C 5.1: 1-(Trimethylsilyl)imidazole / tetrahydrofuran / 2.67 h / 170 °C / Microwave irradiation |
Multi-step reaction with 5 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 0 - 21 °C / Inert atmosphere 1.2: 24 h / 21 - 90 °C 2.1: triethylamine / tetrahydrofuran / 16 h / 21 - 80 °C / Sealed tube; Inert atmosphere 3.1: triethylamine / dichloromethane / 5 h / 21 °C / Inert atmosphere 4.1: hydrogen / ethanol / 1 h / 21 °C 5.1: 1-(Trimethylsilyl)imidazole / tetrahydrofuran / 2.67 h / 170 °C / Microwave irradiation |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: N-(4-nitrophenyl)methanesulfonamide With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 21℃; for 0.5h; Inert atmosphere; Stage #2: ethylene dibromide In N,N-dimethyl-formamide; mineral oil at 21 - 90℃; for 24h; Inert atmosphere; | 5.5.1 V-(2-bromoethyl)-/V-(4-nitrophenyl)methanesulfonamide (D9) To a stirred solution of compound D7 (1.0 g, 4.65 mmol) in DMF (10 ml) was added sodium hydride (60% in mineral oil; 320 mg, 7.99 mmol) at 0 °C under inert atmosphere and stirred at approximately 21 °C for 30 min. To this mixture, 1 ,2-dibromoethane (2.18 g, 11.60 mmol) was added at approximately 21 °C. The mixture was heated to 90 °C and stirred for 24 h. The reaction was monitored by TLC. The reaction mixture was cooled to approximately 21 °C, quenched with ice-cold water (30 ml) and extracted with EtOAc (2 x 40 ml). The combined organic extracts were dried with Na2S04, filtered and concentrated in vacuo to obtain the crude product, which was purified by silica gel column chromatography using 5% MeOH/CH2Cl2 to afford 1.2 g of D9 as a mixture containing 40% unreacted starting material. The obtained mixture was directly taken for next reaction without further purification.1H NMR (500 MHz, CDCI3):6 8.29 (d, J = 8.5 Hz, 2H), 7.56 (d, J = 8.5 Hz, 2H), 4.12 (t, J = 7.0 Hz, 2H), 3.44 (t, J = 7.0 Hz, 2H), 3.01 (s, 3H) | |
Stage #1: N-(4-nitrophenyl)methanesulfonamide With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 21℃; for 0.5h; Inert atmosphere; Stage #2: ethylene dibromide In N,N-dimethyl-formamide; mineral oil at 90℃; for 24h; | 6.5.1 6.5.1. N-(2-bromoethyl)-N-(4-nitrophenyl)methanesulfonamide (D9) To a stirred solution of compound D7 (1.0 g, 4.65 mmol) in DMF (10 ml) was added sodium hydride (60% in mineral oil; 320 mg, 7.99 mmol) at 0° C. under inert atmosphere and stirred at approximately 21° C. for 30 min. To this mixture, 1,2-dibromoethane (2.18 g, 11.60 mmol) was added at approximately 21° C. The mixture was heated to 90° C. and stirred for 24 h. The reaction was monitored by TLC. The reaction mixture was cooled to approximately 21° C., quenched with ice-cold water (30 ml) and extracted with EtOAc (2*40 ml). The combined organic extracts were dried with Na2SO4, filtered and concentrated in vacuo to obtain the crude product, which was purified by silica gel column chromatography using 5% MeOH/CH2Cl2 to afford 1.2 g of D9 as a mixture containing 40% unreacted starting material. The obtained mixture was directly taken for next reaction without further purification. 1H NMR (500 MHz, CDCl3): δ 8.29 (d, J=8.5 Hz, 2H), 7.56 (d, J=8.5 Hz, 2H), 4.12 (t, J=7.0 Hz, 2H), 3.44 (t, J=7.0 Hz, 2H), 3.01 (s, 3H) |
|
Stage #1: N-(4-nitrophenyl)methanesulfonamide With sodium hydride In N,N-dimethyl-formamide at 0 - 21℃; for 0.5h; Inert atmosphere; Stage #2: ethylene dibromide In N,N-dimethyl-formamide at 90℃; for 24h; Inert atmosphere; | 6.5.1 6.5.1. N-(2-bromoethyl)-N-(4-nitrophenyl)methanesulfonamide (D9) o a stirred solution of compound D7 (1.0 g, 4.65 mmol) in DMF (10 ml) was added sodium hydride (60% in mineral oil; 320 mg, 7.99 mmol) at 0 °C under inert atmosphere and stirred at approximately 21 °C for 30 min. To this mixture, 1 ,2-dibromoethane (2.18 g, 11.60 mmol) was added at approximately 21 °C. The mixture was heated to 90 °C and stirred for 24 h. The reaction was monitored by TLC. The reaction mixture was cooled to approximately 21 °C, quenched with ice-cold water (30 ml) and extracted with EtOAc (2 x 40 ml). The combined organic extracts were dried with Na2SC>4, filtered and concentrated in vacuo to obtain the crude product, which was purified by silica gel column chromatography using 5% MeOH/CH2Cl2 to afford 1.2 g of D9 as a mixture containing 40% unreacted starting material. The obtained mixture was directly taken for next reaction without further purification.1H NMR (500 MHz, CDCI3):6 8.29 (d, J = 8.5 Hz, 2H), 7.56 (d, J = 8.5 Hz, 2H), 4.12 (t, J = 7.0 Hz, 2H), 3.44 (t, J = 7.0 Hz, 2H), 3.01 (s, 3H) |
Stage #1: N-(4-nitrophenyl)methanesulfonamide With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 21℃; for 0.5h; Inert atmosphere; Stage #2: ethylene dibromide In N,N-dimethyl-formamide; mineral oil at 21 - 90℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 0 - 21 °C / Inert atmosphere 1.2: 24 h / 90 °C 2.1: triethylamine / tetrahydrofuran / 16 h / 80 °C / Sealed tube; Inert atmosphere 3.1: triethylamine / dichloromethane / 5 h / 21 °C / Inert atmosphere 4.1: hydrogen / ethanol / 1 h / 21 °C 5.1: 1-(Trimethylsilyl)imidazole / tetrahydrofuran / 2 h / 170 °C / Microwave irradiation 6.1: hydrogenchloride / 1,4-dioxane; diethyl ether / 1 h / 0 - 21 °C / Inert atmosphere | ||
Multi-step reaction with 6 steps 1.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 0 - 21 °C / Inert atmosphere 1.2: 24 h / 90 °C / Inert atmosphere 2.1: triethylamine / tetrahydrofuran / 16 h / 80 °C / Sealed tube; Inert atmosphere 3.1: triethylamine / dichloromethane / 5 h / 21 °C 4.1: hydrogen / ethanol / 1 h / 21 °C 5.1: 1-(Trimethylsilyl)imidazole / tetrahydrofuran / 2.67 h / 170 °C / Microwave irradiation 6.1: hydrogenchloride / 1,4-dioxane; diethyl ether / 1 h / 0 - 21 °C / Inert atmosphere |
Tags: 5825-62-7 synthesis path| 5825-62-7 SDS| 5825-62-7 COA| 5825-62-7 purity| 5825-62-7 application| 5825-62-7 NMR| 5825-62-7 COA| 5825-62-7 structure
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Precautionary Statements-General | |
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P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
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P272 | Contaminated work clothing should not be allowed out of the workplace. |
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Health hazards | |
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H311 | Toxic in contact with skin |
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H316 | Causes mild skin irritation |
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H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
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H332 | Harmful if inhaled |
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H335 | May cause respiratory irritation |
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Environmental hazards | |
Code | Phrase |
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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 |
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