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Structure of 5815-08-7
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 5815-08-7 |
Formula : | C9H22N2O |
M.W : | 174.28 |
SMILES Code : | CN(C)C(OC(C)(C)C)N(C)C |
MDL No. : | MFCD00042858 |
InChI Key : | HXRAMSFGUAOAJR-UHFFFAOYSA-N |
Pubchem ID : | 79885 |
GHS Pictogram: |
![]() ![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H302-H314-H226 |
Precautionary Statements: | P501-P270-P240-P210-P233-P243-P241-P242-P264-P280-P370+P378-P303+P361+P353-P301+P330+P331-P363-P301+P312+P330-P304+P340+P310-P305+P351+P338+P310-P403+P235-P405 |
Class: | 3(8) |
UN#: | 2733 |
Packing Group: | Ⅲ |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 52.29 |
TPSA ? Topological Polar Surface Area: Calculated from |
15.71 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.6 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.4 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.21 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.54 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.06 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.34 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.54 |
Solubility | 5.04 mg/ml ; 0.0289 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.33 |
Solubility | 8.08 mg/ml ; 0.0464 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.1 |
Solubility | 13.9 mg/ml ; 0.08 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.37 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.26 |
* 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 |
---|---|---|
95% | In N,N-dimethyl-formamide; at 75℃; for 72h;Inert atmosphere; | Methylterephthalonitrile (1.42g, 9.99mmol) and Bredereck's reagent (3.48g, 19.98mmol) were dissolved in DMF (15mL). The reaction mixture was heated at 75°C under nitrogen for 72hrs after which time the solvent was removed in vacuo. Trituration with Pet. Ether gave a bright yellow solid identified as 2-((E)- 2-dimethylamino-vinyl)-terephthalonitrile ester (1.88g, 0.95mmol, 95percent yield). XH NM (CD3OD) delta: 3.20 (6H, s), 5.34 (1H, d, J = 13.4Hz), 7.21 (1H, dd, J = 8.0Hz, 1.4Hz), 7.9 (1H, d, 13.4Hz), 7.61 (1H, d, J = 8.0Hz), 7.94 (1H, d, J =1.2Hz) |
95% | In N,N-dimethyl-formamide; at 75℃; for 72h;Inert atmosphere; | Example 10A. 2-((E)-2-Dimethylamino-vinyl)-terephthalonitrile esterMethylterephthalonitrile (1.42g, 9.99mmol) and Bredereck's reagent (3.48g, 19.98mmol) were dissolved in DMF (15mL). The reaction mixture was heated at 75°C under nitrogen for 72hrs after which time the solvent was removed in vacuo. Trituration with Pet Ether gave a bright yellow solid identified as 2-((E)-2- dimethylamino-vinyl)-terephthalonitrile ester (1.88g, 0.95mmol, 95percent). H NMR (CD3OD) delta: 3.20 (6H, s), 5.34 (1H, d, J = 13.4Hz), 7.21 (1H, dd, J = 8.0Hz, 1.4Hz), 7.9 (1H, d, 13.4Hz), 7.61 (1H, d, J = 8.0Hz), 7.94 (1H, d, J =1.2Hz) |
95% | In N,N-dimethyl-formamide; at 75℃;Inert atmosphere; | Into a 250-mL round-bottom flask, which was purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 2-methylbenzene-l,4-dicarbonitrile (4 g, 28.14 mmol, 1.00 equiv), [(tert-butoxy)(dimethylamino)methyl]dimethylamine (9.8 g, 56.23 mmol, 2.00 equiv) in N,N-dimethylformamide (50 mL). The resulting solution was stirred overnight at 75 °C, and then concentrated under vacuum. The resulting mixture was washed with 50 mL of hexane. The solids were collected by filtration. This provided 5.3 g (95percent) of 2-[(E)-2- (dimethylamino)ethenyl]benzene-l,4-dicarbonitrile as a yellow solid. |
95% | In N,N-dimethyl-formamide; at 75℃;Inert atmosphere; | Step 2. 2-[(E)-2-(dimethylamino)ethenyl]benzene-1,4-dicarbonitrileInto a 250-mL round-bottom flask, which was purged and maintained with an inert atmosphere of nitrogen, was placed a solution of <strong>[55984-93-5]2-methylbenzene-1,4-dicarbonitrile</strong> (4 g, 28.14 mmol, 1.00 equiv), [(tert-butoxy)(dimethylamino)methyl]dimethylamine (9.8 g, 56.23 mmol, 2.00 equiv) in N,N-dimethylformamide (50 mL). The resulting solution was stirred overnight at 75° C., and then it was concentrated under vacuum. The resulting mixture was washed with 50 mL of hexane. The solids were collected by filtration. This provided 5.3 g (95percent) of 2-[(E)-2-(dimethylamino)ethenyl]benzene-1,4-dicarbonitrile as a yellow solid. |
95% | In N,N-dimethyl-formamide; at 75℃; for 72h;Inert atmosphere; | Al. 2-({E)-2-Dimethylamino-vinYl)-terephthalonitrie ester Methylterephthalonitrile (1.42g, 9.99mmol) and Bredereck's reagent (3.48g, 19.98mmol) were dissolved in DMF (15mL). The reaction mixture was heated at 75 *C under nitrogen for 72hrs after which time the solvent was removed in vacuo. Trituration with Pet. Ether gave a bright yellow solid identified as 2-((E)- 2-dimethylamino-vinyl)-terephthalonitrile ester (1.88g, 0.95mmol, 95percent yield). 3H NMR (CD3OD) delta: 3.20 (6H, s), 5.34 (1H, d, J = 13.4Hz), 7.21 (1H, dd, J = 8.0Hz, 1.4Hz), 7.9 (1H, d, 13.4Hz), 7.61 (1H, d, J = 8.0Hz), 7.94 (1H, d, J =1.2Hz) |
In 1,2-dimethoxyethane; at 75℃; for 12h; | Methylterephthalonitrile (1.42 g, 1.0 mmol) and t-butoxybis(dimethylamine)methane (3.5 g, 2.0 mmol) were heated with 15 mL of DML at 75 °C for 12 h under N2. The DMF was removed and hexane was added. The precipitate formed was filtered and dried to give 1.85 g of the desired product. MS: 504.4, (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To 2,6-dimethyl-3-nitrobromobenzene (2.31 g, 10.0 mmol) in anhydrous DMF (15 mL) is added Bredereck's reagent (tert-butoxybis(dimethylamino)methane) (4.35 mL, 21.1 mmol) and the resultant solution is heated at 125 0C for 5h. Upon cooling to ambient temperature, the reaction mixture is diluted with water and extracted with methylene chloride. The organic layer is isolated, dried (Na2SO4), filtered and concentrated in vacuo to give a dark brown oil. The crude mixture is dissolved in acetic acid/water (12 mL of 4:1) and <n="63"/>cooled to 0 C prior to portion-wise addition of zinc dust (6.56 g, 100.4 mmol) over 2 h. On completion of the addition the reaction mixture is stirred at ambient temperature for 1 h prior to heating at 110 0C for 2 h. The resultant reaction mixture is passed through a pad of Celite eluting with methylene chloride. The filtrate was extracted with methylene chloride and the organic layer is isolated, dried (Na2SO4), filtered and concentrated in vacuo. The crude product is purified by silica gel column chromatography eluting with ethyl acetate/heptane to give 4-bromo-5-niethylindole as a dark brown oil which solidified on standing. | ||
STEP A. SYNTHESIS OF 4-BROMO-5-METHYLINDOLE Fuming nitric acid (>90% yellow fuming HNO3) is slowly added to a solution of 2- bromo-m-xylene (20 g, 150 mmol) in acetic acid (100 ml) cooled in an ice bath (above freezing point). The resulting mixture is allowed to warm to room temperature, stirred for 1 hour, and heated at 80C for 2 hours or until the reaction is shown to be complete by GC/MS analysis following micro-scale base work-up. The reaction mixture is cooled to room temperature and poured into ice/water with stirring. The resulting yellow precipitates are collected by suction filtration and air dried to obtain 2,6-dimethyl-3-nitrobromobenzene. Bredereck's reagent (tert-butoxybis (dimethylamino) methane-16 g, 91 mmol) is added at room temperature to a solution of 2,6-dimethyl-3-nitrobromobenzene (20 g, 87 mmol) in anhydrous DMF (120 ml). The reaction mixture is heated at 120-125 C under N2 for 5 hours or until starting material is mostly consumed according to TLC. The reaction mixture is allowed to cool to room temperature, poured into water (300 ml), and extracted with dichloromethane (100 ml x 3). The combined extracts are dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a mixture of enamines as a dark brown oil. This material is carried on to the next step without purification. The crude mixture is dissolved in acetic acid/water (250 ml of 4: 1), cooled to 0C and treated with zinc dust (57 g, 870 mmol) added slowly in portions. After complete addition, the reaction mixture is heated at 110 C for 4h. Zinc is removed by filtration through a celite pad and the filtrate is extracted with dichloromethane (100 ml x 3). The combined extracts are dried over anhydrous sodium sulfate, concentrated and purified by flash chromatography on silica gel (EtOAc/Hexane 1: 20) to obtain 4-bromo-5-methylindole (5.3 g) (21) as a light purple oil. | ||
Fuming nitric acid (>90% yellow fuming HN03) is slowly added to a solution of 2-bromo-m-xylene (20 g, 150 mmol) in acetic acid (100 mL) cooled in an ice bath (above freezing point). The resulting mixture is allowed to warm to room temperature, stirred for 1 h, and heated at 80 C for 2 h or until the reaction is complete by GC/MS analysis following micro-scale base work-up. The reaction mixture is cooled to room temperature and poured into ice/water with stirring. The resulting yellow precipitates are collected by suction filtration and air dried to obtain 2,6-dimethyl-3-nitrobromobenzene. Bredereck's reagent (tert-butoxybis(dimethylamino)methane (16 g, 91 mmol) is added to a solution of 2,6-dimethyl-3-nitrobromobenzene (20 g, 87 mmol) in anhydrous DMF (120 mL) at room temperature. The reaction mixture is heated at 120-125 C under N2 for 5 h or until starting material is mostly consumed according to TLC. The reaction mixture is allowed to cool to room temperature, poured into water (300 mL), and extracted with dichloromethane (100 mL x 3). The combined extracts are dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a mixture of enamines as a dark brown oil. This material is used in the next step without purification. The crude mixture is dissolved in acetic acid/water (250 mL of 4 : 1), cooled to 0 C and treated with zinc dust (57 g, 870 mmol) added slowly in portions. After complete addition, the reaction mixture is heated at 110 C for 4 h. Zinc is removed by filtration through a celite pad and the filtrate is extracted with dichloromethane (100 mL x 3). The combined extracts are dried over anhydrous sodium sulfate, concentrated, and purified by flash chromatography on silica gel (EtOAc/Hexane 1:20) to obtain 4-bromo-5-methylindole as a light purple oil. A solution of 4-bromo-5-methylindole (800 mg, 3.8 mmol) in anhydrous ether (8 mL) is added with stirring to a suspension of potassium hydride (560 mg, 4.2 mmol, 30% dispersion in mineral oil) in anhydrous ether at 0 C under argon. The resulting mixture is cooled to-78 C and tert-butyllithium (4.9 mL of 1.7 M in pentane, 8.4 mmol) is slowly added. The resulting cream- colored mixture is stirred at -78 C for 1 h. Tributylborate (3.1 mL, 11.4 mmol) is slowly added and the reaction mixture is stirred for 1 h at -78 C before being allowed to slowly warm to room temperature. More anhydrous ether is added to facilitate stirring. After stirring for 24 h, the resulting sticky mixture is diluted with ether and transferred in portions with stirring to a precooled solution of 1 M phosphoric acid (50 mL). After stirring for 30 min, the acidic mixture is extracted with diethyl ether (75 mL x 3) and the combined extracts are extracted with 1 N sodium hydroxide (20 mL x 4). The combined base extracts are cooled with an ice bath, acidified with 1 M phosphoric acid and extracted with ethyl acetate (20 mL x 3). The combined extracts are washed with brine (20 mL), dried over anhydrous sodium sulfate, filtered and concentrated to obtain a beige residue. The residue is triturated with hexane to obtain the desired 5-methylindole-4-boronic acid as a beige gum. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | at 100℃; for 6.5h; | Step 2: Synthesis of 1-(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-dimethylamino-propenone. To <strong>[866545-96-2]1-(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-ethanone</strong> (2.25 g, 9.41 mmol) was added tert-butoxybis(dimethylamino)methane (5.83 mL, 28.23 mmol) (neat) and refluxed in an oil bath at 100 C. for 6.5 hours. The reaction was cooled and titrated with diethyl ether. The solid was filtered and dried under vacuum to afford the title compound as an orange powder (1.93 g, 70% yield). 1H NMR (500 MHz, d6-DMSO) delta 8.67 (d, J=2.5 Hz, 1H), 8.37 (s, 1H), 8.31 (d, J=2.0 Hz, 1H), 7.57 (d, J=12.5 Hz, 1H), 5.78 (d, J=12.0 Hz, 1H), 2.49 (s, 6H). |
70% | at 100℃; for 6.5h;Heating / reflux; | To l-(5-bromo-1H -pyrrolo[2,3-b]pyridin-3-yl)-ethanone (2.25 g, 9.41 mmol) was added tert- butoxybis(dimethylamino)methane (5.83 mL, 28.23 mmol) (neat) and refluxed in an oil bath at 100 C for6.5 hours. The reaction was cooled and titrated with diethyl ether. The solid was filtered and dried under vacuum to afford the title compound as an orange powder (1.93 g, 70% yield). 1H NMR (500 MHz, dg-DMSO) delta 8.67 (d, J= 2.5 Hz, 1H), 8.37 (s, 1H), 8.31 (d, J = 2.0 Hz, 1H), 7.57 (d, J = 12.5 Hz, 1H), 5.78(d, J = 12.0 Hz, 1H), 2.49 (s, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | Example 737-(3-Chloro-4-fluorophenyl)-N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-amine hydrochloride; A solution of <strong>[2923-66-2]1-(3-chloro-4-fluorophenyl)ethanone</strong> (51.8 mg, 300 mummol) and tert.-butoxy-bis(dimethylamino)methane (Bredereck reagent) (52.3 mg, 300 mumol) in 1,4-dioxane (2 mL) was heated to reflux for 4 hours. The solvent was evaporated under reduced pressure and to the residue a solution of N3-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-4H-1,2,4-triazole-3,5-diamine (57.1 mg, 0.2 mmol) in acetic acid (1.0 mL) was added and the reaction was heated to 100 C. over night. On cooling to room temperature a light yellow solid precipitated. The precipitate was filtered and washed thoroughly with acetic acid. The solid was suspended in isopropanol and 37% aqueous hydrogen chloride solution was added. The solvent was removed under reduced pressure and the product dried in vacuo. The title compound was obtained as a light yellow solid (60 mg, 62%).MS ISP (m/e): 450.1/452.2 (100/27) [(M+H)+], 228.2 (51), 179.2 (36).1H NMR (DMSO-D6, 300 MHz): delta (ppm)=10.40 (s, 1H), 9.29 (s, 1H), 8.79 (d, 1H), 8.55 (d, 1H), 8.28 (m, 1H), 7.84 (s, 1H), 7.75 (t, 1H), 7.67 (s, 1H), 7.54 (d, 1H), 7.48 (d, 1H), 7.33 (d, 1H), 3.83 (s, 3H), 2.35 (s, 3H), 1.91 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Preparation of intermediate 4-(4-(2-(methylthio)-6-oxo-l,6-dihydropyrimidin-5- yl)pyrimidin-2-ylamino)benzonitrile (34) : (34)5-Acetyl-2-(methylthio)pyrimidin-4(3H)-one (33) (1.094 g, 5.94 mmol) was dissolved in l-tert-butoxy-N,N,N',N'-tetramethylmethanediamine (12.26 mL, 59.4 mmol), then the reaction mixture was heated at 120C for 6 hours. The reaction mixture was concentrated in vacuo, and dried over high vacuum for 1 hour. The crude intermediate was taken up in DMF (31.6 mL), then l-<strong>[5637-42-3](4-cyanophenyl)guanidine</strong> (2.076 g, 8.91 mmol) and K2C03 (4.10 g, 29.7 mmol) were added. The reaction mixture was heated at 120C for 48 hours. Additional 1 -<strong>[5637-42-3](4-cyanophenyl)guanidine</strong> (2.076 g, 8.91 mmol) and K2C03 (3.69 g, 26.7 mmol) were added, and the reaction mixture was stirred at 120C for additional 18 hours. The reaction mixture was cooled to rt, then was slowly poured into an ice-cooled IN HCl solution while stirring vigorously. The reaction mixture was neutralized with additional IN HCl, then the reaction mixture was allowed to stir for an additional 30 minutes. The resulting precipitate was filtered, washed multiple times with DI water, 2-propanol, then diethyl ether. The resulting crude product was dried over high vacuum for 18 hours to obtain the desired product as a red/brown solid (940 mg, 47% yield). MS (ES+): m/z = 337.2 (100) [MH+]. HPLC: tR = 1.35 minutes over 3 minutes. Purity: 72% [HPLC (LC/MS) at 220 nm]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70.1% | In N,N-dimethyl-formamide; at 143℃; for 3h; | ethyl 2-(2-(dimethylamino)vinyl)-4-nitrobenzoate [00148] To Intermediate 3A (1 1.35 g, 58.2 mmol) in DMF (15 ml) was added l-tert- butoxy-N,N,N',N'-tetramethylmethanediamine (39.6 ml, 192 mmol). The mixture was heated at 143 C for 3.0 h. DMF was removed by vacuum distillation at 70 C to leave a semi solid. The semi-solid was triturated with EtOAc/hexanes (1 :4) and stored at 4 C overnight. The precipitate was collected by filtration to give Intermediate 3B (10.2 g, 40.8 mmol, 70.1% yield) as a dark solid. lR NMR (400 MHz, chloroform-d) delta ppm 8.21 (d, J=2.20 Hz, 1 H) 7.87 (d, J=8.79 Hz, 1 H) 7.66 (dd, J=8.79, 2.20 Hz, 1 H) 7.02 (d, J=13.19 Hz, 1 H) 6.12 (d, J=13.74 Hz, 1 H) 3.91 (s, 3 H) 2.94 (s, 6 H). |
69.7% | In N,N-dimethyl-formamide; at 143℃; for 3h; | Intermediate 3 B: 2-((E)-2-Dimethylamino-vinyl)-4-nitro-benzoic acid methyl ester j00130j To Intermediate 3A (6.6 g, 33.8 mmol) in DMF (9.0 mL) was added 1-tert- butoxy-N,N,N?,N?-tetramethylmethanediamine (23.04 mL, 112 mmol). The mixture washeated at 143 C for 3 h. The crude reaction mixture was vacuum distilled at 70 C toleave a semi-solid. The semi-solid was triturated with EtOAc/Hexanes (1:4) and stored at4 C overnight. The precipitate was collected by filtration to give Intermediate 3B (5.9 g,23.58 mmol, 69.7 % yield) as a dark solid. ?H NMR (400 MHz, CHLOROFORM-cl) oeppm 8.21 (d, J=2.20 Hz, 1 H) 7.87 (d, J=8.79 Hz, 1 H) 7.66 (dd, J=8.79, 2.20 Hz, 1 H)7.02 (d, J=13.19 Hz, 1 H) 6.12 (d, J=13.74 Hz, 1 H) 3.91 (s, 3 H) 2.94 (s, 6 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | In N,N-dimethyl-formamide; at 70℃; for 2.0h; | A mixture of <strong>[939-83-3]2-methyl-5-nitrobenzonitrile</strong> (235a) (5 g, 30.8 nunol) and 1-ten- butoxy-N,N,N?,N?-tetramethylmethanediamine (Bredereck?s reagent) (10.19 mL, 49.3 mmol) in dry DMF (lO mL) was heated at 70 C for 2 Ii. The reaction was cooled to room temperature and concentrated in vacuum; the crude product was triturated with 120 mL ofhexanes/ethyl acetate (5:1), and stirred for JO mm. The solid obtained was collected by filtration washed with hexanes (2 x 75 mL), dried under vacuum to afford (E)-2-(2- (dimethylamino)vinyl)-5-nitrobenzonirrile (235b) (6.07 g, 91 % yield) as a light brown solid; ?H NMR: ?H NMR (300 IvIHz, DMSO-d6) oe 8.35 (d, .1= 2.5 Hz, 1 H), 8.06 (ddd, .1 = 9.2, 2.6, 0.7 Hz, I H), 7.93 (d, J= 13.0 Hz, I H), 7.70 (d, J 9.4 Hz, 1 H), 5.29 (d, J = 12.9Hz, IH), 3.04 (s, 6H); MS (ES-) 252.1 (M+Cl). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | General procedure: A mixture of ethyl 2-(2-ethoxy-2-oxoethyl)-4,5-dimethoxybenzoate(5, 210 mg, 0.70 mmol) and tBuOCH(NMe2)2 (240 mg, 1.4mmol) was stirred at 100 C for 3 h. After cooling, to the mixturewere added AcOH (3 ml) and 4-ethylaniline (250 mg, 2.1 mmol),then stirred at room temperature for 2 h. After removal of AcOHin vacuo (with toluene twice), to the residue were added NaOH(220 mg, 5.6 mmol) and EtOH (7 mL), then stirred at 80 C for 1h. After cooling, were added water and 12 M aqueous HCl, thenthe precipitate was collected by filtration. The precipitate waswashed with water and Et2O to give 6b (250 mg, 99%) as a palebeige solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69 g | In N,N-dimethyl-formamide; at 140℃; for 3h; | To a solution of El (93 g, 476 mmol) in DMF (45 mL) was added l-tert-butoxy-N,N,N',N'- tetramethyl-methanediamine (249 g, 1.43 mol, 295 mL). The reaction mixture was stirred at l40C for 3 hr to give a brown mixture. TLC showed new spot. The mixture was cooled to room temperature and stirred at 0C for 30 min. Solid was precipitated out. After filtration, the filter cake was washed with EtOAc/PE and dried under reduced pressure to give compound E2 (69 g) as a purple powder. |
Tags: 5815-08-7 synthesis path| 5815-08-7 SDS| 5815-08-7 COA| 5815-08-7 purity| 5815-08-7 application| 5815-08-7 NMR| 5815-08-7 COA| 5815-08-7 structure
A482910 [36805-97-7]
1,1-Di-tert-butoxy-N,N-dimethylmethanamine
Similarity: 0.61
A482910 [36805-97-7]
1,1-Di-tert-butoxy-N,N-dimethylmethanamine
Similarity: 0.61
A482910 [36805-97-7]
1,1-Di-tert-butoxy-N,N-dimethylmethanamine
Similarity: 0.61
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H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
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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 |
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H351 | Suspected of causing cancer |
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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 |
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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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