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CAS No. : | 103-76-4 |
Formula : | C6H14N2O |
M.W : | 130.19 |
SMILES Code : | C(CN1CCNCC1)O |
MDL No. : | MFCD00005970 |
InChI Key : | WFCSWCVEJLETKA-UHFFFAOYSA-N |
Pubchem ID : | 7677 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H315-H318 |
Precautionary Statements: | P264-P280-P302+P352-P305+P351+P338-P332+P313-P362+P364 |
* 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 |
---|---|---|
94.6% | at 204℃; for 2.25 h; Autoclave | A magnetically-stirred 70-mL fluoropolymer-lined steel autoclave was fitted with an internal thermocouple capable of determining the temperature of the liquid phase contained in the vessel, a pressure gauge, a pressure-relief valve, and a vent valve. The amine starting material, anhydrous or aqueous sodium 2-hydroxyethanesulfonate, and anhydrous or aqueous sodium hydroxide were charged to the open autoclave, which was then assembled and immersed in an electrically heated oil bath. With the vent valve closed, the stirred reaction mixture was rapidly heated to the reaction temperature and held at that temperature for the times specified in Examples 9, 10, and 13 below. The reaction mixture was then cooled to ambient temperature, the reactor opened, and the reaction product taken up in sufficient water to dissolve all solids. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89.8% | Example 1: synthesis of 2-(4-(6-chloro-2-methylpyrimidin-4-yl) piperazin-1-yl) ethanol (Compound 4); 1-(2-hydroxyethyl) piperazine (Compound 3) (16.6g, 127.6mmol)) and 2-methyl-4,6-dichloropyrimidine (Compound 2) (10.4g, 63.8mmol) were mixed with methylene dichloride (80mL) in reaction flask to be stirred for 2.5h at 30C, and then triethylamine (1.8mL) was added with the reaction overnight in thermal insulation. After vacuum filtration, the cake was rinsed by methylene dichloride. The filtrate was vacuum condensed to dry, and then n-hexane (40mL) was added to grow the grains for 1h by stirring. After vacuum filtration, the cake was rinsed by n-hexane (20mL) and dried at 40C to constant weight to give white solid target Compound 4 (14.7g, yield: 89.8%). Element analysis: C11H17ClN4O, Calculated: C, 51.46; H, 6.67; N, 21.82; Found: C, 51.45; H, 6.69; N, 21.82. | |
89.8% | [0138]1-(2-hydroxyethyl)piperazine (Compound 3) (16.6 g, 127.6 mmol)) and 2-methyl-4,6-dichloropyrimidine (Compound 2) (10.4 g, 63.8 mmol) were mixed with methylene dichloride (80 mL) in reaction flask to be stirred for 2.5 h at 30 C., and then triethylamine (1.8 mL) was added with the reaction overnight in thermal insulation. After vacuum filtration, the cake was rinsed by methylene dichloride. The filtrate was vacuum condensed to dry, and then n-hexane (40 mL) was added to grow the grains for 1 h by stirring. After vacuum filtration, the cake was rinsed by n-hexane (20 mL) and dried at 40 C. to constant weight to give white solid target Compound 4 (14.7 g, yield: 89.8%).[0139]Element analysis: C11H17ClN4O, Calculated: C, 51.46; H, 6.67; N, 21.82. Found: C, 51.45; H, 6.69; N, 21.82. | |
85% | In dichloromethane; at 20℃; | General procedure: 4,6-dichloro-2-methylpyrimidine 10a (1 mmol) and corresponding piperazine (2 mmol) were mixed in CH2Cl2 (40 mL) and stirred at room temparature overnight. The mixture was purified by flash chromatography (DCM: MeOH = 20:1) to give the product 1e-g. |
85% | In dichloromethane; at 20℃; | A mixture of 4,6-dichloro-2-methylpyrimidine (162 mg, 1 mmol) and 1-(2-ethanol)-ylpiperazine (260 mg, 2 mmol) was stirred in dichloromethane (40 mL) at room temperature overnight. After the nucleophilic substitution reaction, after TLC monitoring the reaction, The product 1c (218mg) was isolated through a silica gel column, a white solid, melting point: 72 C, The yield was 85% and the purity was 95%. |
83% | To a solution of 4,6-dichloro-2-methylpyrimidine (2.86 g, 17.5 mmol) in 1,4- dioxane (200 niL) was added 2~(piperazin-l-yl)ethanol (1.14 g, 1.08 mmol) and N5N- diisopropylethylamine (12.2 mL, 70 mmol). The reaction mixture was stirred overnight at room temperature. The solvent was removed in vacuo. The residue was dissolved in EtOAc (150 mL) and washed with saturated NaHCO3 (2 x 50 mL). The organic layer was dried (Na2SO4). The solvent was removed in vacuo to afford the crude product (1.86 g, 83%) as yellow oil. | |
39% | With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane;Heating / reflux; | Example 145 Synthesis of 2-(4-{6-[7-(2,6-dichloro-phenyl)-5-methyl-benzo[1,2,4]triazin-3-ylamino]-2-methyl-pyrimidin-4-yl}-piperazin-1-yl)-ethanol To synthesize the title compound (CLXIX), two intermediate compounds 62 (2-[4-(6-chloro-2-methyl-pyrimidin-4-yl)-piperazin-1-yl]-ethanol) and 63 (7-(2,6-dichloro-phenyl)-5-methyl-benzo[1,2,4]triazin-3-ylamine) shown below were used. To synthesize compound 62, to a solution of 4,6-dichloro-2-methyl-pyrimidine (5.0 g, 31 mmol) and 2-piperazin-1-yl-ethanol (2.7 g, 21 mmol) in dioxane (25 mL) was added DIPEA (3.0 mL, 17 mmol). The mixture was heated at reflux for 16 h. The mixture was allowed to cool to room temperature and poured into water. The reaulting aqueous layer was extracted with EtOAc and the combined organic layers washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated and the residue purified by flash chromatography on silica gel (5-10% MeOH/DCM) to afford compound 62 as a brown liquid (2.1 g, 39%). MS (ESI+): m/z 257. |
39% | With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; for 16h;Heating / reflux; | Example 127. 2-[4-(6-Chloro-2-methvl-pyrimidin-4-vl)-piperaziii-l-vll-ethano?71); [0307] To a solution of 4,6-dichloro-2-methyl-pyrimidine (5.0 g, 31 mmol) and 2- piρerazin-1-yl-ethanol (2.7 g, 21 mmol) in dioxane (25 mL) was added DEPEA (3.0 mL, 17 mmol). The mixture was heated at reflux for 16 h. The mixture was allowed to cool to room temperature and poured into water. The resulting aqueous layer was extracted with EtOAc and the combined organic layers washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated and the residue purified by flash chromatography on silica gel (5-10% MeOH/DCM) to afford the title compound as a brown liquid (2.1 g, 39%). MS (ES+): m/z 257 (M+H)+. |
2-Piperazin-1-yl-ethanol (8.2g, 63.1 mmol) was added to a solution of 4,6-dichloro-2- methylpyrimidine (5.2g, 31.9 mmol) in dichloromethane (80 ml) at rt. The mixture was stirred for two hours and triethylamine (0.9 ml) was added. The mixture was stirred at rt for 20h. The resultant solid was filtered. The cake was washed with dichloromethane (20 ml). The filtrate was concentrated to give an oil. This oil was dried under high vacuum for 20h to give a solid. This solid was stirred with heptane (50 ml) at rt for 5h. Filtration gave 7C (8.13g) as a white solid | ||
4.08 g | To a solution of 4,6-dichloro-2-methylpyrimidine (3.00 g) in dichloromethane (35 mL) was added 2-(piperazin-1-yl)ethanol (4.51 mL) at room temperature, and the mixture was stirred for 4 hr. To the reaction mixture was added triethylamine (0.513 mL) at room temperature, and the reaction mixture was stirred overnight. The resulting solid was collected by filtration, washed with dichloromethane, and dried under reduced pressure to give the title compound (4.08 g). 1H NMR (400 MHz, CDCl3) δ 2.48 (3H, s), 2.55-2.63 (6H, m), 3.63-3.73 (6H, m), 6.34 (1H, s) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83.2% | To a mixture of compound 5D (4.00 g, 10.14 mmol) and hydroxyethylpiperazine (6.60 g, 50.69 mmol) in n-butanol (40 mL) was added DIPEA (3.53 mL, 20.26 mmol). The slurry was heated at 118°C for 4.5h, then cooled slowly to room temperature. The solid was collected by vacuum filtration, washed with n- butanol (5 mL), and dried. The product (5.11 g) was dissolved in hot 80percent EtOH-H2O (80 mL), and the solution was clarified by filtration. The hot solution was slowly diluted with water (15 mL) and cooled slowly to room temperature. The solid was collected by vacuum filtration, washed with 50percent ethanol-water (5 mL) and dried affording 4.27 g (83.2 percent yield) of N- (2-chloro-6-methylphenyl)-2- (6- (4- (3- hydroxyethyl) piperazin-1-yl)-2-methylpyrimidin-4-ylamino) thiazole-5-carboxamide as monohydrate. 1H NMR (400 MHz, DMSO-d6) # 2.23 (s, 3H), 2.40 (s, 3H), 2.42 (t, 2H, J=6), 2.48 (t, 4H, J=6.3), 3.50 (m, 4H), 3.53 (q, 2H, J=6), 4.45 (t, 1H, J=5.3), 6.04 (s, 1H), 7.25 (t, 1H, J=7.6), 7.27 (dd, 1H, J=7.6, 1.7), 7.40 (dd, 1H, J=7.6, 1.7), 8.21 (s, 1H), 9. 87 (s, 1H), 11.47. | |
Example 23; Procedure for the Preparation of Dasatinib Form H1-7 (Monohydrate)A mixture of compound 1 (133.9 mg, 0.5 mmol), N-(2-hydroxyethyl)piperazine (260.4 mg, 2 mmol) and N-ethyldiisopropylamine (0.174 ml, 1 mmol) in DMF (0.5 ml) was stirred at 100° C. for 2.5 h. H2O (3 ml) was added to the solution at the same temperature. A gummy product precipitated. The suspension was allowed to cool slowly to room temperature and stirred for 2 h at room temperature. The product was filtered washed with H2O (2.x.) and dried on the filter. Yield: 140 mg. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate; In isopropyl alcohol; | Step A Preparation of 1-[4-(2-hydroxyethyl)-1-piperazino]-6,7-dimethoxyisoquinoline A mixture of 2.6 g. of <strong>[21560-29-2]1-chloro-6,7-dimethoxyisoquinoline</strong> and 6.0 g. of 2-hydroxyethylpiperazine is heated at 140C. for 2 hours and then combined with 50 ml. of isopropanol and 2 g. of sodium carbonate. The resulting mixture is refluxed for 15 minutes, filtered, evaporated in vacuo to an oil which is purified by chromatography on silica gel to obtain 1-[4-(2-hydroxyethyl)-1-piperazino]-6,7-dimethoxyisoquinoline, m.p. 115-118C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With trifluoroacetic acid; In water; acetonitrile; | EXAMPLE 135 3-[4-(2-hydroxyethyl)-1-piperazinyl]carbonyl}-6-methyl-2-pyridinol The desired product was prepared by substituting <strong>[38116-61-9]2-hydroxy-6-methylnicotinic acid</strong> for 6-methylnicotinic and 2-(1-piperazinyl)ethanol for 2-methylpyrrolidine in Example 1. After workup the crude compound was purified by HPLC on a C-18 column with a solvent system increasing in gradient over 50 minutes from 5% to 100% acetonitrile/water containing 0.01% TFA to provide the desired product as the trifluoroacetate salt. MS m/e 266 (M+H)+; 1H NMR (DMSO-d6) delta 2.19 (s, 3H), 2.35-2.39 (br m, 2H), 2.55 (br t, 2H), 2.98 (br t, 2H), 3.19 (br t, 2H), 3.47-3.56 (m, 4H), 4.38 (br s, 1H), 6.04 (d, 1H), 7.36 (d, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In 1,4-dioxane; at 70 - 80℃; for 12 - 48h;Combinatorial reaction / High throughput screening (HTS); | Example 1. Preparation of a combinatorial library of substituted 2-aminomethyl-5-hydroxy-1H-indole-3-carboxylic acids esters of general formula 1.1. A mixture of 0.357 mmol of ester 2, 0.43 mmol of a secondary amine 3, and 0.43 mmol of formaldehyde in the form of formalin in 3 ml of dioxane is heated at 70-80°C at stirring for 12 to 48 hours. Progress of the reaction is monitored by chromato-mass-spectrometry. Upon completion of the reaction, the reaction mass is diluted with water, the residue is filtered and recrystallized from a suitable solvent, or purified by chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In tetrahydrofuran; at 20℃; | General procedure: To a solution of <strong>[10241-97-1]5-methyl-1H-indole-2-carboxylic acid</strong> (20) (263mg, 1.50mmol) in THF (7mL) were added 2-(piperidin-4-yl)ethanol (213mg, 1.65mmol), 1-hydroxybenzotriazole (HOBt, 101mg, 0.750mmol), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDAC) hydrochloride (316mg, 1.65mmol), followed by stirring at room temperature for 14h. The reaction mixture was partitioned between ethyl acetate and 0.5M aqueous hydrochloric acid. The organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and then concentrated in vacuo. The residue was recrystallized from ethyl acetate/acetonitrile (5mL/2mL) to give 3 (365mg, 85.0percent) as a beige powder. |
Tags: 103-76-4 synthesis path| 103-76-4 SDS| 103-76-4 COA| 103-76-4 purity| 103-76-4 application| 103-76-4 NMR| 103-76-4 COA| 103-76-4 structure
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H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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