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Structure of 5799-75-7
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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. : | 5799-75-7 |
Formula : | C8H13N |
M.W : | 123.20 |
SMILES Code : | C#CCN1CCCCC1 |
MDL No. : | MFCD00510920 |
InChI Key : | LQSQLFOKTMSBEC-UHFFFAOYSA-N |
Pubchem ID : | 336652 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H226-H335-H314 |
Precautionary Statements: | P210-P240-P241-P242-P243-P260-P264-P271-P280-P301+P330+P331-P303+P361+P353-P304+P340-P305+P351+P338-P310-P363-P370+P378-P403+P233-P403+P235-P405-P501 |
Class: | 3(8) |
UN#: | 2733 |
Packing Group: | Ⅲ |
* 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 |
---|---|---|
67% | With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; | General procedure: To a mixture of propargyl bromide (8.47 mmol) and secondary amine (16.94 mmol) in DMF, K2CO3(25.41 mmol) was added and the reaction mixture was allowed to stir at ambient temperature for 10-12 h. The reaction mixture was then quenched with ice cold water and extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulphate and the solvent was evaporated under reduced pressure to obtain the corresponding products. |
66% | With potassium carbonate; In tetrahydrofuran; for 6h;Reflux; | General procedure: A solution of 3-bromopropyne (1.0 equiv), amine (1.0 equiv) and K2CO3 (2.0 equiv) in THF was stirred at reflux for 6 h. The solvent was removed and the residue was partitioned between water andCH2Cl2. The organic layer was dried over magnesium sulfate andunder reduced pressure. The crude product was further purified bysilica gel column chromatography to give the desiredpropargylamine. 4.1.10.1 1-(Prop-2-ynyl)piperidine (13b) This compound was prepared from 3-bromopropyne (500 mg, 4.24 mmol), piperidine (360 mg, 4.24 mmol) and K2CO3 (1.17 g, 8.48 mmol) according to the general synthesis procedure C to afford the title compound (344 mg, 2.80 mmol, 66% yield) as a viscous oil. ESI-MS: m/z = 124 [M+H]+. |
56% | With caesium carbonate; In acetone; toluene; at 20℃; for 18h; | Example 16; Preparation of 1-(3-fluoro-4-(2-(3-(piperidin-1-yl)prop-1-ynyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-3-(2-phenylacetyl)thiourea; Step A: Preparation of 1-(prop-2-ynyl)piperidine; Prepared using methodology as described in US 2005/0026944. To a stirred mixture of piperidine (851 mg, 10.0 mmol), cesium carbonate (3.26 g, 10.0 mmol) and acetone (20 mL) was added 3-bromoprop-1-yne (1.49 g, 10.0 mmol; 80% in toluene) at room temperature. The white suspension was stirred for 18 hours at room temperature. The suspension was filtered, and the filtrate was concentrated. The resulting residue was triturated with diethyl ether (10 mL), filtered, and the filtrate concentrated to obtain the product as an oil (0.70 g, 56%). 1H NMR (400 MHz, CDCl3) delta 3.27 (d, J=2 Hz, 2H), 2.50 (m, 4H), 2.22 (t, J=2 Hz, 1H), 1.62 (m, J=6 Hz, 4H), 1.43 (m, 2H). |
In diethyl ether; at 0 - 20℃; | To a solution of piperidine (8.5 ml) in diethyl ether (100 ml) was added propargyl bromide (3 ml) on an ice bath, the solution was stirred overnight at room temperature, then diethyl ether was added thereto followed by filtering, and the solvent was evaporated in vacuo to provide the title compound (6.0 g).1H-NMR (400MHz, CDCl3); 5 (ppm): 1.39-1.47 (m, 2H), 1.58-1.66 (m, 4H), 2.23 (t, 1H), 2.45-2.56 (m, 4H), 3.28 (d, 2H). | |
With caesium carbonate; In acetone; at 0 - 20℃; | General procedure: Propargyl bromide (0.5 mmol) was dropwise added to a mixture of Cs2CO3 (0.5 mmol), acetone (30 mL) and the corresponding secondary amine (0.5 mmol) at 0 C. The mixture was stirred overnight at room temperature and then filtered. The filtrates was evaporated to dryness to afford the target productes as an orange-brown oil. which was directly used for the next step without purification. | |
With potassium carbonate; In N,N-dimethyl-formamide; toluene; at 0 - 25℃;Inert atmosphere; | General procedure: To a mixture of nucleophile (1 mmol) and potassium carbonate (2.0 mmol) in DMF (10 ml) at 0 C, was added 80 % solution of propargyl bromide in toluene (1.2 mmol) over 5 min. After stirring reaction mixture for 30 min, slowly raised temperature to 25 C and stirred further till completion. The crude mixture was quenched with cold water (15 ml) followed by the addition of diethyl ether (15 ml). The ether layer formed was separated and washed twice with cold water (10 ml), dried over anhydrous Na2SO4. Removal of solvent under vacuum afforded the crude product (1a-1p) which was purified by column chromatography | |
With sodium hydrogencarbonate; In acetonitrile; at 20℃; | General procedure: To a solution of amine (8mmol) in 4mL of acetonitrile, 3-bromoprop-1-yne (2mmol) was added in drops at room temperature, followed by sodium bicarbonate (8mmol) and the resulting mixture was stirred at room temperature overnight. The next step was carried in the same reaction pot. First, 4-azido-7-chloro-quinoline (1mmol) dissolved in enough CH2Cl2 was added to the reaction, followed by a 2mL of a freshly prepared aqueous solution of sodium ascorbate, made using ascorbic acid (53mg, 0.3mmol), NaHCO3 (25mg, 0.3mmol) and CuSO4.5H2O (0.3mmol). The reaction mixture was stirred for 24h, then 30mL CH2Cl2 was added, washed with water (3×40mL), the organic layer was dried over anhydrous Na2SO4, and evaporated to dryness. The resulting residue was purified by preparative TLC to afford the final compound. | |
With potassium carbonate; In N,N-dimethyl-formamide; toluene; at 0 - 25℃;Inert atmosphere; | General procedure: To a mixture of nucleophile (1 mmol) and potassium carbonate (2.0 mmol) in DMF (10 ml) at 0 C, was added 80 % solution of propargyl bromide in toluene (1.2mmol) over 5 min. After stirring reaction mixture for 30 min, slowly raised temperature to 25 C and stirred further till completion. The crude mixture was quenched with cold water (15 ml) followed by the addition of diethyl ether (15 ml). The ether layer formed was separated and washed twice with cold water (10 ml), dried over anhydrous Na2SO4. Removal of solvent under vacuum afforded the crude product (1a-1p) which was purified by column chromatography. | |
at 0 - 20℃; for 10h; | General procedure: To 33% dimethylamine solution (3.8 mL, 25.0 mmol) was added 3-bromo-propyne (0.88 mL, 11.3 mmol) dropwise at 0 C. The reaction solution was stirred for 10 h at room temperature and filtered to remove the solid. The filter cake was rinsed with THF (15 mL). The combined filtrate was concentrated in vacuo to afford N,N-dimethylprop-2-yn-1-amine (382 mg, 41%). To N,N-dimethylprop-2-yn-1-amine (382 mg, 4.6 mmol) was added 48 (1.00 g, 3.9 mmol), copper (I) iodide (74.3 mg, 0.39 mmol) and triethylamine (0.63 mL, 4.6 mmol) at room temperature. The mixture was stirred at 70 C for 7 h. After diluted with ethyl acetate (30 mL), it was washed twice with saturated NH4Cl aqueous solution and brine, dried over Na2SO4, filtered and evaporated in vacuo. The residue was purified by silica gel chromatography (CH2Cl2/ MeOH) to afford 42c as a white solid (1.0 g, 76%). | |
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; | General procedure: The starting reactants (2a-2e) were synthesized by drop wise addition of propargyl bromide (1.2 mmol) to the stirred solution of secondary amines (1a-1e, 1.0 mmol) in dimethylformamide in the presence of potassium carbonate (2.0 mmol) as a base, stirring was continue for 4-5 h at room temperature. After the completion of reaction as indicated by TLC water was added in the reaction mixture. The product was extracted with ethyl acetate from the reaction mixture. The separated organic layer was evaporated under reduced pressure to get N-substituted(prop-2-yn-1yl)amines (2a-2e). For synthesis of 2-bromo-N-arylacetamides (4a-4e), to the stirred solution of aromatic amines (3a-3e, 1.0 mmol) in dichloromethane, 2-bromoacetyl bromide (1.2 mmol) was added in the presence of potassium carbonate at 0-5 C and stirring of the mixture was continued for 15-20 minutes at the same temperature. After the completion of reaction dilute hydrochloric acid was added, solid product was precipitated out which was filtered and dried. Further to synthesize target triazoles (5a-5y) 2-bromo-N-arylacetamides (4a-4e, 1.0 mmol) dissolved in dimethylformamide, aqueous sodium azide (3.0 mmol) was added and stirring was continued at 25-40 C for 30 min. To this mixture N-substituted(prop-2-yn-1yl)amines (2a-2e, 1.0 mmol), aqueous copper sulphate pentahydrate (0.1 mmol) and sodium ascorbate (0.4 mmol) were added and stirring was continued for 6-10 h at same temperature. After completion of reaction, ice cold water was added to reaction mixture, precipitated product was filtered and washed with ammonia solution. Crude products were washed with ethyl acetate and dried under vacuum to get pure product in good yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol; at 25℃; for 3h; | Preparation of the starting material 1-(2-propynyl)piperidine: With stirring, a solution of 2-propynyl chloride (40.31 g) in dry methanol (50 ml) was added dropwise to a solution of piperidine (92.14 g) in dry methanol (100 ml). The mixture was stirred at 25 C. for 3 hours and then filtered. The filtrate was concentrated under reduced pressure and the residue was distilled (boiling point: 163-165 C./atmospheric pressure). |