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CAS No. : | 53617-35-9 | MDL No. : | MFCD03274733 |
Formula : | C9H18N2O | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | - |
M.W : | 170.25 | Pubchem ID : | - |
Synonyms : |
|
Signal Word: | Warning | Class: | |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | |
Hazard Statements: | H315-H319-H335 | Packing Group: | |
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 potassium carbonate; In acetonitrile; at 100℃; | <strong>[454-16-0]1-fluoro-2-methoxy-4-nitrobenzene</strong> (5000 mg, 29.22 mmol), 4-(piperidin-4-yl)morpholine (4974 mg, 29.22 mmol), potassium carbonate (80764 mg, 58.44 mmol) in acetonitrile (45 ml) was stirred at 100° C. for overnight. The reaction was diluted with ethyl acetate, washed with water, dried, concentrated and purified by flash chromatography (silica gel) to provide 4-(1-(2-methoxy-4-nitrophenyl)piperidin-4-yl)morpholine. LCMS-ESI+ (m/z): [M+H]+ calcd for C16H23N3O4: 321.4. found: 322.0 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81.9% | To a 100 mL three-necked flask was added 1.70 g (0.01 mol) of 4- (4-piperidinyl) morpholine and 40 mL of anhydrous tetrahydrofuran, and after cooling to 0 to 5 C, To the system was slowly added 0.48 g (0.012 mol) of 60% sodium hydride. After stirring for 15 min, 3.30 g (0.007 mol) of Ethyl-6,6-dimethyl-8-trifluoroacetate-11-oxa-6-11-dihydro-5H-benzo [b] carbazole-3-carbonitrile was dissolved in 20 mL Tetrahydrofuran was added dropwise to the reaction system and the temperature was raised to room temperature. After stirring for 3 to 4 hours, 20 mL of water was added to the reaction solution to quench the reaction. The resulting solution was extracted three times with dichloromethane and the resulting organic phase was concentrated under reduced pressure to a solid precipitate which was recrystallized from a mixture of methanol / water = 1: 1 to give a white solid Alectinib, 2.77 g (0.006 mol). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With sodium methylate; In N,N-dimethyl-formamide; at 100℃; for 12.0h; | 9-ethyl-8-iodo-6,6-dimethyl-11-oxo-5H,6H,11H-benzo[b]carbazole-3-carbonitril (5.0 g,Was dissolved in N, N-dimethylformamide (120 mL) and 4- (4-piperidinyl) morpholine (4.4 g, 26 mmol)(1.5 g, 28 mmol). The reaction mixture was stirred at 100 C for 12 hours. The reaction mixture was cooled to room temperature, water (45 mL) was added, cooledCrystallization was carried out at 0 C for 4 hours and filtered to give alectinib, a white solid (4.9 g) in 92% yield. |
89% | With sodium methylate; In toluene; at 100℃; for 10.0h; | 9-Ethyl-6,6-dimethyl-8-iodo-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile(4.40 g, 10 mmol) was added to 30 ml of toluene.Add 4-(4-piperidinyl)morpholine (3.4 g, 20 mmol),Sodium methoxide (1.08 g, 20 mmol), reacted at 100 C for 10 h, cooled to room temperature.Add 20 ml of water, cool to -10 C for 3 hours, filter,Get alectinib (4.29g, 8.9mmol),Mass Spectrum (ESI): M/Z = 483.24 (M+H), purity 93%, yield 89%. |
10.3 g | With potassium tert-butylate; L-proline; In 1,4-dioxane; at 120℃; for 24.0h;Inert atmosphere; | The 9-ethyl-8-iodo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo [b] carbazole-3-carbonitrile obtained as the starting material ( 10.7g, 0.021mol)With 4- (4-piperidinyl) morpholine (8.3 g, 0.048 mol),Potassium tert-butoxide (108mg, 0.001mol),L-proline (105mg, 0.001mol) was dissolved in 1,4-dioxane under the protection of N2, and reacted at 120 C for 24h.After the reaction of the raw materials was detected by TLC, it was extracted three times with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and recrystallized with ethanol.Yield 10.3 g of white solid,Its reaction formula is as follows: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22.8 g | With sulfuric acid; sodium hydrogensulfite; at 230℃; under 22502.3 Torr; | 9-Ethyl-6,6-dimethyl-8-hydroxy-11-oxa-6,11-dihydro-5H-benzo[b] produced in Step HCarbazole-3-carbonitrile 9 (11.27 g, 3.77 mol) and 4-morpholin-4-yl-piperidine (16.8 g, 4.9 mol)After mixing, it is added to the reaction vessel.In the presence of 100 ml of 85% concentrated sulfuric acid solution, add the catalyst sodium bisulfite to fully mix and stir.Increase pressure to 3MPa, increase temperature to 230C,Condensation reaction occurs. After the reaction is complete, the mixture is cooled and cooled. Ethyl acetate is added for extraction 3 times. The aqueous phase is collected, and the precipitated solid is stirred and filtered. The filter cake is recrystallized to give 9-ethyl-6,6-dimethyl-8- (4-Morpholin-4-yl-piperidin-1-yl)-11-oxa-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 10 (22.8 g, 8.7 Mol). |
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