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Chemical Structure| 473927-69-4 Chemical Structure| 473927-69-4

Structure of 473927-69-4

Chemical Structure| 473927-69-4

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Product Details of [ 473927-69-4 ]

CAS No. :473927-69-4
Formula : C15H17IN2O2
M.W : 384.21
SMILES Code : O=C1C(N2CCOCC2)=CCCN1C3=CC=C(I)C=C3
MDL No. :MFCD18072445
InChI Key :UWWMPOYYIGCWEH-UHFFFAOYSA-N
Pubchem ID :22240453

Safety of [ 473927-69-4 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Application In Synthesis of [ 473927-69-4 ]

* 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.

  • Downstream synthetic route of [ 473927-69-4 ]

[ 473927-69-4 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 473927-69-4 ]
  • [ 675-20-7 ]
  • Cu(PPh3)3Br [ No CAS ]
  • [ 545445-44-1 ]
YieldReaction ConditionsOperation in experiment
With ammonium hydroxide; caesium carbonate; In ethyl acetate; toluene; Part B. Soluble copper(I)-catalyzed Ullmann coupling reaction. A suspension of 1-(4-iodo-phenyl)-3-morpholin-4-yl-5,6-dihydro-1H-pyridin-2-one (10, 2.2 g, 5.73 mmol), piperidin-2-one (42, 851 mg, 8.59 mmol, 1.5 equiv), and Cs2CO3 (3.73 g, 11.46 mmol, 2.0 equiv) in toluene (15 mL) was treated with Cu(PPh3)3Br (1.065 g, 1.146 mmol, 20% equiv) at room temperature under N2, and the resulting reaction mixture was degassed three times under a steady stream of nitrogen. The reaction mixture was warmed up to reflux for 6 h. When HPLC showed the Ullmann coupling reaction was complete, the reaction mixture was cooled down to 5-10 C. before being quenched with 14% of ammonium hydroxide aqueous solution (20 mL) and EtOAc (30 mL) at 5-10 C. The mixture was stirred for an additional 4 h at 25 C. The two layers were then separated, and the aqueous layer, was extracted with EtOAc (3*20 mL). The combined organic extracts were washed with saturated NaCl aqueous solution (10 mL), dried over MgSO4, and concentrated in vacuo. The residue was directly purified by flash column chromatography (SiO2, 15-40% EtOAc/hexane gradient elution) to afford the desired 3-morpholin-4-yl-1-[4-(2-oxo-piperidin-1-yl)-phenyl]-5,6-dihydro-1H-pyridin-2-one (63, 1.568 g, 2.036 g theoretical, 77%) as a pale-yellow oil, which solidified upon standing at room temperature in vacuo. For 63, CIMS m/z 356 (M++H, C2OH25N3O3).
  • 2
  • [ 473927-69-4 ]
  • [ 27143-07-3 ]
  • [ 473927-64-9 ]
YieldReaction ConditionsOperation in experiment
75% With triethylamine; In ethyl acetate; at 0℃; for 2h;Inert atmosphere; Cooling with ice; Reflux; The preparation was carried out in an inert atmosphere (argon). 2-Chloro-2-[2-(4- methoxyphenyl)hydrazono] acetic acid ethyl ester (14.1 g; 0.055 mol) was dissolved in 140 ml of ethyl acetate. The solution was cooled to 0-5°C in an iced water bath. The solution being stirred, 1-(4-iodophenyl)-3-morpholin-4-yl-5,6-dihydro-1H-pyridin-2-one (21.1 g; 0.055 mol) was added in portions. After stirring up, triethylamine (11.1 g; 0.110 mol) was added dropwise to the reaction mixture at 0-5 °C. The cooling of the reaction mixture was interrupted and the temperature was left to rise to the room level. Then, heating was started up to reflux. The reflux temperature of the reaction mixture was maintained for ca. 120 min. Completion of the reaction was monitored by means of HPLC. The reaction mixture was cooled to 0-5°C again and concentrated hydrochloric acid (27.5 ml; 0.275 mol) diluted with distilled water in the 1 :1 ratio was slowly added dropwise. Being cooled, the reaction mixture was stirred for ca. 1 h. Then, another 55 ml of water was added and the resulting suspension was stirred for another 2 h while being cooled. The separated product was isolated by filtration and dried in vacuo at 50°C for 24 h. The product III was obtained in the yield of 21.3 g; i.e. 75 percent and HPLC quality of 95 percent.
30.4% Step-2: Ethyl 6-(4-iodophenyl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H- pyrazolo [3,4-cJ pyridine-3-carboxylate 1 -(4-Iodophenyl)-3 -morpholine-5,6-dihydro-2H-pyridin-2-one (100 g, obtained in step-i), <strong>[27143-07-3]ethyl 2-chloro-2-(2-(4-methoxyphenyl)hydrazono)acetate</strong> (100 g) and triethylamine (131.6g) were added to toluene (1000 ml) at room temperature. The resulting mixture was heated to reflux and then stirred for 2 hours at reflux. The reaction mass was cooled to room temperature, followed by filtration and then washing with toluene (50 ml x 2). The resulting toluene layer was washed with water (200 ml x 2), followed by distillation of toluene layer under vacuum at 90°C to obtain a residue (164 g). 4N Hydrochloric acid (79.2g) and dichloromethane (315 ml) were added to the resulting residue and then stirred for 2 hours at room temperature. The reaction mass was washed with 2percent sodium bicarbonate solution (200 ml), followed by washing with water (200 ml) and then adjusting the pH to 6. The resulting dichioromethane layer was treated with carbon (10 g), followed by distillation under vacuum at 55°C to obtain a residue (175 g). Acetone (200 ml) was addedto the resulting residue and then stirred for 30 minutes at room temperature. The resulting mass was cooled to 0-5°C for 30 minutes and then stirred for 30 minutes. The separated solid was filtered, washed with chilled acetone (70 ml) and then dried the material at 65°C for 3 hours to produce 102 g of ethyl 6-(4-iodophenyl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7- tetrahydro- 1 H-pyrazolo[3 ,4-c]pyridine-3 -carboxylate (Purity by HPLC: 99percent; overall yield:30.4percent).
  • 3
  • [ 473927-69-4 ]
  • [ 27143-07-3 ]
  • C26H29IN4O5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In toluene;Reflux; Intermediate-B (25g, 0.065 moles) toluene (250 ml), Intermediate-A (20.68g, 0.08 moles)and TEA (lOg, 0.099 moles); were heated to reflux for 2-3 hrs progress of the reaction is monitored on TLC or HPLC. Distilled out toluene from reaction mass under reduced pressure below 70°C to obtain thick brown mass. To this add 400 ml methanol, cooled to 25-30°C and slowly add TFA (15g, 0.135 moles). Reaction mass was then stirred at RT for 1.0-I.5 hr reaction monitored on TLC or HPLC. Solid was isolated by filtration flush with fresh 25 ml methanol. Dried at 60-65°C to obtain Intermediate-D 29.6 gm (88percent yield) and HPLC purity >99percent without any purification.
  • 4
  • [ 473927-69-4 ]
  • [ 675-20-7 ]
  • [ 545445-44-1 ]
YieldReaction ConditionsOperation in experiment
84% With bromotris(triphenylphosphine)copper(I); In 5,5-dimethyl-1,3-cyclohexadiene;Dean-Stark; Reflux; Example-5 Preparation of 3-morpholin-4-yl-1-[4-(2-oxo-piperidin-1-yl)-phenyl]-5,6-dihydro-1H-pyridin-2-one A suspension of 1-(4-iodo-phenyl)-3-morpholin-4-yl-5,6-dihydro-1H-pyridin-2-one (75 g, 0.194 moles), 2-piperidone (48 g, 0.485 moles) and tripotassium phosphate (103 g, 0.485 moles) in xylene (750 ml) was treated with Cu(PPh3)3Br (54.5 g, 0.058 moles) at room temperature and heated to reflux by using a dean stark water separator for 8-10 hrs. After completion, the reaction mass was cooled to 0-5 C. Aqueous ammonia (750 ml) and ethyl acetate (1125 ml) were added to the reaction mixture and stirred for 2-3 hrs. The resultant solid was filtered and washed with ethyl acetate (20 ml) to get a solid, which was dissolved in methylene dichloride (375 ml) at 35-40 C. and treated with activated carbon. The resultant solution was filtered through a hyflow bed and distilled under vacuum to get an residue; followed by addition of methanol (90 ml) and the reaction mass was cooled to 0-5 C., stirred for 1 hr at the same temperature and filtered to get a solid material. The obtained solid was washed with methanol to get 59 g (84%) of the title compound with >99% purity.
84% With potassium phosphate; bromotris(triphenylphosphine)copper(I); In 5,5-dimethyl-1,3-cyclohexadiene;Reflux; Dean-Stark; A suspension of l-(4-iodo-phenyl)-3-morpholin-4-yl-5,6-dihydro-lH-pyridin-2-one (75 g, 0.194 moles), 2-piperidone (48 g, 0.485 moles) and tripotassium phosphate (103 g, 0.485 moles) in xylene (750 ml) was treated with Cu(PPh3)3Br (54.5 g , 0.058 moles) at room temperature and heated to reflux by using a dean stark water separator for 8-10 hrs. After completion, the reaction mass was cooled to 0-5C. Aqueous ammonia (750 ml) and ethyl acetate (1125 ml) were added to the reaction mixture and stirred for 2-3 hrs. The resultant solid was filtered and washed with ethyl acetate (20 ml) to get a solid, which was dissolved in methylene dichloride (375 ml) at 35-40C and treated with activated carbon. The resultant solution was filtered through a hyflow bed and distilled under vacuum to get an residue; followed by addition of methanol (90 ml) and the reaction mass was cooled to 0-5C, stirred for 1 hr at the same temperature and filtered to get a solid material. The obtained solid was washed with methanol to get 59 g (84%) of the title compound with > 99% purity.
35 g Example-8 Preparation of 3-morpholino-1-(4-(2-oxopiperidin-1-yl)phenyl)-5,6-dihydro pyridin-2(1H)-one (Formula-8) A mixture of 1-(4-iodophenyl)-3-morpholino-5,6-dihydropyridin-2(1H)-one compound of formula-7 (50 g), piperidin-2-one (32.25 g) and o-xylene (75 ml) was stirred for 10 minutes at 25-30 C. Potassium carbonate (27.0 g), followed by copper iodide (7.43 g) were added to the reaction mixture. The reaction mixture was heated to 140-145 C. under azeotropic distillation condition and stirred for 6 hours at the same temperature. Cooled the reaction mixture to 35-40 C., water (175 ml) was slowly added to the reaction mixture at 35-40 C. Cooled the reaction mixture to 10-15 C. and ammonia (125 ml) was added to the reaction mixture at 10-15 C. The temperature of the reaction mixture was raised to 25-30 C. and stirred for 2 hours at the same temperature. Filtered the precipitated solid, washed with water and then dried to get title compound. Yield: 35 gm; MR: 195-200 C.; HPLC purity: 95%.
  • 5
  • [ 473927-69-4 ]
  • [ 4775-98-8 ]
  • 5,6-dihydro-3-(4-morpholinyl)-1-[4-(2-oxo-6-methyl-1-piperidinyl)phenyl]-2(1H)-pyridone [ No CAS ]
YieldReaction ConditionsOperation in experiment
61% With tris(triphenylphosphine) copper(I) bromide; caesium carbonate; In chloroform; at 62℃; for 81h;Inert atmosphere; Nitrogen protection, plus compound V (2.2 g, 5.73 mmol, 1 equiv), <strong>[4775-98-8]6-methylpiperidin-2-one</strong> (0.97 g, 8.59 mmol, 1.5 equiv), cesium carbonate (5.6 g, 17.2 mmol, 3 equiv) was dissolved in 15 ml of chloroform and added, followed by Cu(Ph3P)3Br (3.16 g, 3.4 mmol, 0.59 equiv), plus chloroform 70ml, heated at 62 C, 6 hours after the point board reaction, 75 hours after the reaction is completed. Post-treatment: quenched with 14% ammonia in mass percentage (the mass concentration refers to the mass of ammonia) as a percentage of the total mass of the aqueous ammonia reagent) filter, filter cake retained. Dispensing, water layer of dichloromethane wash 15ml × 3, dissolve the filter cake, the organic layer. Saturated salt water washed 120ml × 1. Dried over anhydrous magnesium sulfate. Steamed, ethanol beating and drying to give 1.29 g of product, yield 61%.
 

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