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Chemical Structure| 147403-65-4

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Product Details of [ 147403-65-4 ]

CAS No. :147403-65-4
Formula : C25H24N4O4
M.W : 444.48
SMILES Code : O=C(C1=C2N(CC3=CC=C(C4=CC=CC=C4C(NO)=N)C=C3)C(OCC)=NC2=CC=C1)OC
MDL No. :MFCD21496678
Boiling Point : No data available

Safety of [ 147403-65-4 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis of [ 147403-65-4 ]

* 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 [ 147403-65-4 ]

[ 147403-65-4 ] Synthesis Path-Downstream   1~16

  • 1
  • [ 139481-44-0 ]
  • [ 147403-65-4 ]
YieldReaction ConditionsOperation in experiment
90% With hydroxylamine hydrochloride; sodium hydrogencarbonate; In N,N-dimethyl acetamide; water; at 70℃; for 18h; N, N-dimethylacetamide 2L,Water 16L, added to the reaction bottle,Hydroxylamine hydrochloride (3.37 kg 48.6 mol) was added,Sodium carbonate (5.15 kg 48.6 mol) was added,<strong>[139481-44-0]1-[(2'-cyanobiphenyl-4-yl)methyl]-2-ethoxybenzimidazole-7-carboxylic acid methyl ester</strong>(2 kg, 4.86 mol)70 ° C for 18 hours,Cooling, adding water 2L,Precipitation of solid,Filtration was 2-ethoxy-1-[2'-(N'-hydroxycarbamimidoyl)biphenyl-4-yl]-1H-benzimidazole-7-carboxylic acid methyl ester (1.94 g, 37.70 mol),Reference is made to Examples1HPLC conditions Purity: 98.9percent Yield: 90percent.
85% With hydroxylamine hydrochloride; sodium hydrogencarbonate; In dimethyl sulfoxide; at 80 - 85℃; for 20h; Dimethyl sulfoxide (75 mL) and hydroxylamine hydrochloride (6 g) were stirred at 20°C to 30°C. Sodium bicarbonate (9 g) was added to the solution and stirred at 45 °C to 50 °C for 1 hour. Methyl-1-[(2'-cyanobiphenyl-4-yl)methyl]-2-ethoxy-1H-benzimidazole-7-carboxylate (3 g) was added to the reaction mixture and heated at 80 °C to 85 °C for 20 hours. The reaction mixture was cooled to 20 °C to 30 °C and de-ionized water (75 mL) was added to the reaction mixture. The solid obtained was filtered and washed with water (75 mL). The solid obtained was purified in 2-butanol (15 mL) at 90 °C to 95 °C for 4 hours and further cooled to 20 °C to 30 °C for 4 hours. The solid obtained was filtered, washed with 2-butanol (6 mL), and dried to obtain the title compound. Yield: 2.75 g (85percent) HPLC Purity: 96.89percent
75% With hydroxylamine hydrochloride; sodium carbonate; In N,N-dimethyl-formamide; at 60℃; for 24h; 60 g of N,N-dimethylformamide was added to the reaction flask.Add 19.5 g of sodium carbonate with stirring and mix well.Add 8.5 g of hydroxylamine hydrochloride and warm to 35 ° C.The reaction was stirred for 30 minutes and 25 g of compound IV-1 was added.Continue to raise the temperature to 60 ° C, stir the reaction for 24 h, after the reaction is over,The crystallized crystals were cooled and filtered to obtain a crude compound III-1. The crude product obtained,DMSO was added to the reaction flask, and the temperature was crystallized for 1 hour, and the temperature was crystallized.Filtration and drying gave Compound III-1 in a yield of 75percent.
70.4% With hydroxylamine hydrochloride; sodium carbonate; In dimethyl sulfoxide; at 90℃; To a 500 mL four-neck flask, 20 g of Compound 1 was added, and while stirring, 100 mL of dimethyl sulfoxide solution in which 10.14 g (3 eq) of hydroxylamine hydrochloride was added was added, and the mixture was heated to 90 DEG C and 30.95 g (6 eq) was added in portions under stirring. Sodium carbonate, after the completion of the reaction for 9-10 hours, after the completion of the reaction, it is allowed to come to room temperature, and 100 mL of water is added to stir the mixture. The solid precipitates, which is cooled down to 0-5°C. Stirring is continued for about 1 hour, and the mixture is dried by suction to obtain 15.2 g of compound 2. The yield was 70.4percent.
35% With hydroxylamine hydrochloride; triethylamine; In dimethyl sulfoxide; at 20 - 75℃; for 6h; Weighed hydroxylamine hydrochloride (60.8mmol), triethylamine (63.2mmol), dimethyl sulfoxide 60mL was added to a 100mL two-neck round bottom flask, stirred at room temperature for 30min, added to the reaction system1-[(2'-Cyanobiphenyl-4-yl)methyl]-2-ethoxy-1H-benzimidazole-7-carboxylic acid methyl ester (6.08 mmol) was reacted at 75 ° C for 6 h and the reaction was completed. Thereafter, the mixture was cooled to room temperature, and the product in the reaction mixture was extracted with dichloromethane, distilled under reduced pressure, solvent was removed, and recrystallized to give 1-[(2'-(hydroxyindolyl)[1,1-biphenyl]- Methyl 4-yl)methyl]-2-ethoxy-1H-benzimidazole-7-carboxylate, yield 35percent.
With hydroxylamine hydrochloride; sodium hydrogencarbonate; In dimethyl sulfoxide; at 25 - 90℃; for 18h; Example 1Preparation of methyl 2-ethoxy [[2'-(hydroxyamidino) biphenyl-4-yl] methyI]-lH- benzimidazole-7-carboxylateTo a solution of hydroxylamine hydrochloride (122 g) and dimethylsulfoxide (1000 ml), Sodium bicarbonate (204 g) was added at 25-30°C, which was further heated to 45-50°C. To the resulting solution l-[(2'cyanobiphenyl-4-yl)methyl]-2-ethoxy benzimidazole-7-carboxylate (40 g) was added and the resulting solution was heated to 85-90°C followed by stirring at the same temperature for about 18 h. Reaction mass was cooled to 15-20°C. Water was added and the solution was stirred for 15-20 min at 15- 20°C. The product was filtered, washed and dried to obtain title compound. (Yield: 38 g; 88percent; (Purity: 87percent with amide impurity 3.86percent.
55 g With hydroxylamine hydrochloride; sodium hydroxide; In methanol; N,N-dimethyl acetamide; at 10 - 75℃; for 0.5h;Inert atmosphere; Methanol (400 mL) and sodium hydroxide (56.44 g) were added under a nitrogen atmosphere and stirred at 20° C. to 30° C. to get a clear solution. Dimethylacetamide (750 mL) and hydroxylamine hydrochloride (101.45 g) were added under a nitrogen atmosphere and stirred at 20° C. to 30° C. to get clear solution. Methanolic sodium hydroxide solution was added to the solution of hydroxylamine hydrochloride in dimethylacetamide at 25° C. to 30° C. The reaction mixture was stirred for 30 minutes. Methyl-1-[(2'-cyanobiphenyl-4-yl)methyl]-2-ethoxy-1H-benzimidazole-7-carboxylate (100 g) was added to the reaction mixture at 25° C. to 30° C. and heated to 70° C. to 75° C. for 16 hours to 20 hours. The reaction mixture was cooled to 10° C. to 15° C. The reaction mixture was added to deionized water (1000 mL) at 10° C. to 25° C. The pH of the reaction mixture was adjusted to 0.8 to 1.2 using concentrated hydrochloric acid (150 mL). The reaction mixture was stirred for 30 minutes at 20° C. to 30° C. The reaction mixture was filtered through celite and washed with deionized water (100 mL). The aqueous layer was washed with toluene (500 mL) at 25° C. to 30° C. and the pH of the aqueous layer was adjusted to 8.8 to 9.2 using 30percent solution of sodium carbonate (500 mL) at 20° C. to 30° C. The reaction mixture was stirred for 3 hours to 4 hours at 25° C. to 30° C. The reaction mixture was filtered and washed with deionized water (100 mL) at 20° C. to 30° C. Isobutanol (500 mL) was added to the reaction mixture at 20° C. to 30° C. and the reaction mixture was heated to 90° C. to 95° C. The reaction mixture was stirred for 2 hours at 90° C. to 95° C., cooled to 25° C. to 30° C., and stirred for 4 to 6 hours at 25° C. to 30° C. The reaction mixture was filtered and washed with isobutanol (100 mL) at 20° C. to 30° C. The reaction mixture was dried under vacuum for 30 minutes at 20° C. to 30° C. and then at 45° C. to 50° C. to obtain the title compound. Yield: 55 g
191.3g With hydroxylamine hydrochloride; sodium hydrogencarbonate; sodium sulfite; In dimethyl sulfoxide; at 50 - 85℃; for 12h; Taking anhydrous sodium sulfite 122.5 g (0.972 mol)Sodium bicarbonate 408.4 g (4.861 mol)Was added to 2.4 L of DMSO, stirred,A mixture of hydroxylamine hydrochloride (270.2 g, 3.889 mol)Temperature control 50 ~ 55 stirring reaction 2h,Was added 1 - [(2 - cyanobiphenyl-4-yl) methyl] -2-ethoxy-benzimidazole-7-carboxylate (200g, 0.486mol),Temperature control 80 ~ 85 stirring reaction 10h,Rapid dropwise addition of 2.4L water stirring crystallization,Temperature control 20 ~ 25 stirring for 1h,Filtration to give compound II191.3g.HPLC was used to detect compound II 99.07percent and amide impurity 0.32percent.
With tetrabutyl-ammonium chloride; hydroxylamine; triethylamine; In ethanol; water; for 30h;Reflux; Add 1000g to the 20L reaction bottleMethyl 2-ethoxy-1-((2'-cyanobiphenyl-4-yl)methyl)-1H-benzimidazole-7-carboxylate (II),1473 mL of 50percent aqueous hydroxylamine solution, 340 mL of triethylamine, 1 g of sodium hexametaphosphate, 0.5 g of tetrabutylammonium chloride and 8 L of industrial ethanol (95percent ethanol). The reaction solution was heated to reflux for 30 h, slightly cooled, and filtered while hot. After cooling and crystallization for 8 h, the solid obtained by suction filtration was dried at 45 ° C for 8 h to obtain white solid intermediate III 910 g, yield: 91.5percent, purity 91.7percent.

  • 3
  • [ 530-62-1 ]
  • [ 147403-65-4 ]
  • [ 147403-52-9 ]
YieldReaction ConditionsOperation in experiment
85% With 1,8-diazabicyclo[5.4.0]undec-7-ene; In dimethyl sulfoxide; at 20℃; for 3h;Product distribution / selectivity; Example 4Methyl 2-ethoxy- 1 -((2'-(5-oxo-4,5-dihydro- 1 (2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)- 1H- benzo[< ]imidazole-7-carboxylate of formula la l ,8-Diazabicyclo[5.4.0.]undec-7-ene (DBU; 0.1 g, 0.65 mmol) was added dropwise to a mixture of methyl 2-methoxy- l -((2'-((hydroxyamino)iminomethyl)biphenyl-4-yl)methyl)- lH- benzo[i ]imidazole-7-carboxylate (of formula Va; 0.22 g, 0.5 mmol), the corresponding solvent (3 ml) and carbonyldiimidazole (0.1 g, 0.6 mmol) in a reaction vial under stirring and the mixture was stirred at the room temperature for 3 hours. Then, the content of the vial was poured into water ( 10 ml) and, after acidification with acetic acid, the separated solids were aspirated and washed with water. The yields and purity of the products are summarized in Table I. Table I - Yield and purity of the product of Example 4* - Also contains 40.4 percent of the starting compound of formula Va; ** - Carbonyl-di- 1 ,2,4- triazole was used instead of carbonyldiimidazole.
68% Example 2Preparation of methyl l-[[2'-(4, 5-dihydro-5-oxo-4H-l, 2, 4-oxadiazol-3-yl) biphenyl- 4-yl] methyl]-2-ethoxy-lH-benzimidazole-7-carboxyIate To a solution of methyl 2-ethoxy [[2'-(hydroxyamidino) biphenyl-4-yl] methyl]- lH-benzimidazole-7-carboxylate (25 g) in tetrahydrofuran (700 ml), N,N- carbonyldi imidazole (15 g) and l,8-diazabicyclo[5.4.0]undec-7-ene (DBU)(13 g) was added and resulting solution was stirred for 30-40 mins. at about 20-25°C. To the resulting solution ethyl acetate (700 ml) and saturated solution of sodium bisulphite (700 ml) was added. Organic layer was separated, washed with brine solution and evaporated under vacuum to concentrate the solution. Reaction mass was cooled to 20-25°C and cyclohexane was added to it and the solution was stirred for about 20-25°C. Product was filtered and dichloromethane was charged to it followed by stirring. The product was filtered, washed and dried to obtain title compound. (Yield: 17.8 g; 68percent (Purity: 96percent with desethyl impurity 0.1 1percent)
  • 5
  • [ 616-38-6 ]
  • [ 147403-65-4 ]
  • [ 147403-52-9 ]
YieldReaction ConditionsOperation in experiment
78.7% With sodium methylate; In methanol; for 48h;Reflux;Product distribution / selectivity; Example 13 Methyl 2-ethoxy- 1 -((2'-(5-oxo-4,5-dihydro- 1 ,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)- 1 H- benzo[t/]imidazole-7-carboxylate of formula laA 30percent solution of MeONa in methanol (0.33 g, 1.8 mmol) was added to a suspension of methyl 2-ethoxy- 1 -((2'-((hydroxyamino)iminomethyl)biphenyl-4-yl)methyl)- 1 H-benzo [d] - imidazole-7-carboxylate (of formula Va; 0.44 g, 1 mmol) in methanol (10 ml) and the mixture was stirred at the room temperature for 10 minutes. As the mixture was still very thick, more methanol (10 ml) was added and subsequently dimethyl carbonate (DMC; 0.2 g, 2.2 mmol) was added and the mixture was stirred under moderate reflux for 24 hours. The mixture contained 26.9 percent of the starting compound of formula Va and 62.4 percent of the compound of formula la according to HPLC. A second portion of DMC (0.4 g, 4.4 mmol) was added and the mixture was stirred under moderate reflux for another 24 hours. The mixture contained 12.9 percent of the starting compound of formula Va and 73.4 percent of the compound of formula la according to HPLC. After evaporation the residue was dissolved in water (20 ml) and the solids separated after acidification with 5percent HC1 were aspirated and washed with water. 0.35 g (78.7 percent) of a product was obtained, containing 95.2 percent of the compound of formula la according to HPLC.
  • 6
  • [ 102-09-0 ]
  • [ 147403-65-4 ]
  • [ 147403-52-9 ]
  • [ 108-95-2 ]
YieldReaction ConditionsOperation in experiment
69.7%Chromat.; 14.9%Chromat. With potassium carbonate; In dimethyl sulfoxide; at 20℃; for 2h;Product distribution / selectivity; Example 10Methyl 2-ethoxy- l -((2'-(5-oxo-4,5-dihydro-l ,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)- lH- benzo[ai]irnidazole-7-carboxylate of formula laA mixture of methyl 2-ethoxy- l -((2'-((hydroxyamino)iminomethyl)biphenyl-4-yl)methyl)- l H- benzo[ii|imidazole-7-carboxylate (of formula Va; 0.1 g, 0.22 mmol), DMSO (2 ml), the corresponding carbonate (0. 1 g; DMC = dimethyl carbonate, DEC = diethyl carbonate, DPC = diphenyl carbonate) and the corresponding base (0.05 g) was stirred in a reaction vial at the room temperature for 2 hours. The results are summarized in Table IV. Table IV - Yield and purity of the product of Example 10
  • 7
  • [ 102-09-0 ]
  • [ 147403-65-4 ]
  • [ 147403-52-9 ]
YieldReaction ConditionsOperation in experiment
74.4% With potassium carbonate; In dimethyl sulfoxide; at 20℃; for 4h; Example 12Methyl 2-ethoxy-l -((2'-(5-oxo-4,5-dihydro-l ,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)- lH- benzo[.pound. ]imidazole-7-carboxylate of formula laDiphenyl carbonate (DPC; 0.32 g, 1 .5 mmol) was added to a mixture of methyl 2-ethoxy-l- ((2'-((hydroxyamino)iminomethyl)biphenyl-4-yl)methyl)- lH-benzo[i/]imidazole-7- carboxylate (of formula Va; 0.44 g, 1 mmol), DMSO (10 ml) and K2C03 (0.2 g, 1 .4 mmol) and the mixture was stirred at the room temperature for 2 h. The mixture contained 12.4 percent of the starting compound of formula Va, 8.3 percent of phenol and 71.8 percent of the substance of formula la according to HPLC. After stirring at the room temperature for another 2 hours the reaction mixture was poured into water (25 ml) and, after acidification with acetic acid, the separated solids were aspirated and washed with water. 0.43 g (91.4 percent) of a product containing 93.2 percent of the compound (la) according to HPLC was obtained. Crystallization from ethyl acetate yielded 0.35 g (74.4 percent) of a compound with the melting point 194-197 °C with the HPLC purity of 98.8 percent.
  • 8
  • [ 147403-65-4 ]
  • [ 503-38-8 ]
  • [ 147403-52-9 ]
YieldReaction ConditionsOperation in experiment
53.1% With pyrographite; triethylamine; In tetrahydrofuran; at 20 - 100℃; for 5h; Example 19Methyl 2-ethoxy- 1 -((2'-(5-oxo-4,5-dihydro- 1 ,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)- 1 H- benzo[c ]imidazole-7-carboxylate of formula laFirst, active carbon (0.1 g) and then a solution of diphosgene (0.15 g, 0.75 mmol) in THE (1 ml) were added to a mixture of methyl 2-ethoxy- 1 -((2'-((hydroxyamino)iminomethyl)- biphenyl-4-yl)methyl)-l H-benzo[(i]imidazole-7-carboxylate (of formula Va; 0.44 g, 1 mmol), THF (10 ml) and triethylamine (0.5 g, 5 mmol) and the mixture was stirred in a closed pressure flask at the room temperature for 1 hour. Then, the temperature was increased to 100 °C and the mixture was stirred at this temperature for 4 hours. After cooling down, water (20 ml) was added under stirring and, after stirring for 30 minutes, the active carbon was aspirated through kieselguhr. The filtration cake was washed with 5 percent ammonia (5 ml). The filtrate was then acidified with acetic acid and the resulting mixture was extracted with ethyl acetate (2 x 25 ml). After washing with water (5 5 ml) the extract was dried and after evaporation 0.4 g of a product was obtained, which contained 66.3 percent of the compound of formula la according to HPLC. Centrifugal chromatography (Cyclograph from Analtech, plate thickness 2 mm, dichloromethane-methanol 20 : 1 to 10 : 1 system) and subsequent crystallization from ethyl acetate yielded 0.25 g (53.1 percent) of a product, which contained 99.8 percent of the compound of formula la according to HPLC.
  • 9
  • [ 41864-22-6 ]
  • [ 147403-65-4 ]
  • [ 147403-52-9 ]
YieldReaction ConditionsOperation in experiment
With 1,8-diazabicyclo[5.4.0]undec-7-ene; In dimethyl sulfoxide; at 20℃; for 3h;Product distribution / selectivity; Example 4Methyl 2-ethoxy- 1 -((2'-(5-oxo-4,5-dihydro- 1 (2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)- 1H- benzo[< ]imidazole-7-carboxylate of formula la l ,8-Diazabicyclo[5.4.0.]undec-7-ene (DBU; 0.1 g, 0.65 mmol) was added dropwise to a mixture of methyl 2-methoxy- l -((2'-((hydroxyamino)iminomethyl)biphenyl-4-yl)methyl)- lH- benzo[i ]imidazole-7-carboxylate (of formula Va; 0.22 g, 0.5 mmol), the corresponding solvent (3 ml) and carbonyldiimidazole (0.1 g, 0.6 mmol) in a reaction vial under stirring and the mixture was stirred at the room temperature for 3 hours. Then, the content of the vial was poured into water ( 10 ml) and, after acidification with acetic acid, the separated solids were aspirated and washed with water. The yields and purity of the products are summarized in Table I. Table I - Yield and purity of the product of Example 4* - Also contains 40.4 percent of the starting compound of formula Va; ** - Carbonyl-di- 1 ,2,4- triazole was used instead of carbonyldiimidazole
  • 10
  • [ 32315-10-9 ]
  • [ 147403-65-4 ]
  • [ 147403-52-9 ]
YieldReaction ConditionsOperation in experiment
59.5% With triethylamine; In tetrahydrofuran; at 80℃; for 8h; Example 17Methyl 2-ethoxy- l -((2'-(5-oxo-4,5-dihydro-l ,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)- l H- benzo[.pound./]imidazole-7-carboxylate of formula la Solid triphosgene (0.12 g, 0.4 mmol) was added to a mixture of methyl 2-ethoxy-l -((2'- ((hydroxyamino)iminomethyl)biphenyl-4-yl)methyl)-lH-benzo[i/]imidazole-7-carboxylate (of formula Va; 0.44 g, 1 mmol), THF (10 ml) and triethylamine (0.5 g, 5 mmol) and the mixture was stirred in a closed pressure flask at the temperature of 80 °C for 8 hours. After cooling water (20 ml) was added under stirring and, after stirring for 30 minutes, the mixture was acidified with acetic acid. The separated honey-like product was extracted with ethyl acetate, the extract was dried and evaporated to dryness. 0.45 g of a product was obtained, which contained 65.5 percent of the compound of formula la according to HPLC. Double crystallization from ethyl acetate yielded 0.28 g (59.5 percent) of a product, which contained 95.2 percent of the compound of formula la.
  • 11
  • [ 147403-65-4 ]
  • [ 105-58-8 ]
  • [ 147403-52-9 ]
YieldReaction ConditionsOperation in experiment
9.1%Chromat. With sodium ethanolate; In dimethyl sulfoxide; at 20℃; for 2h; Example 10Methyl 2-ethoxy- l -((2'-(5-oxo-4,5-dihydro-l ,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)- lH- benzo[ai]irnidazole-7-carboxylate of formula laA mixture of methyl 2-ethoxy- l -((2'-((hydroxyamino)iminomethyl)biphenyl-4-yl)methyl)- l H- benzo[ii|imidazole-7-carboxylate (of formula Va; 0.1 g, 0.22 mmol), DMSO (2 ml), the corresponding carbonate (0. 1 g; DMC = dimethyl carbonate, DEC = diethyl carbonate, DPC = diphenyl carbonate) and the corresponding base (0.05 g) was stirred in a reaction vial at the room temperature for 2 hours. The results are summarized in Table IV. Table IV - Yield and purity of the product of Example 10
  • 12
  • [ 139481-44-0 ]
  • [ 139481-33-7 ]
  • [ 147403-65-4 ]
YieldReaction ConditionsOperation in experiment
With hydroxylamine hydrochloride; triethylamine; In dimethyl sulfoxide; for 0.5h;Product distribution / selectivity; Example 9Ethyl 2-ethoxy-l -((2'-((hydroxyamino)iminomethyl)biphenyl-4-yl)methyl)-lH-benzo[c ]- imidazole-7-carboxylate (lb) - modification of the process (J Med. Chem. 1996, 39(26), 5228-5235)Triethylamine (3.4 ml = 2.48 g) was added to a suspension of hydroxylamine hydrochloride (1.7 g, 25 mmol) in DMSO (8 ml) and the mixture was stirred at the laboratory temperature for 15 minutes. The thick slurry was then aspirated and washed with tetrahydrofuran (10 ml). The filtrate was concentrated in vacuo (most tetrahydrofuran evaporated). The nitrile (IVa; 2.06 g, 5 mmol) was added to this solution and the mixture was stirred at the laboratory temperature for 15 minutes. Then, the mixture was partitioned into 4 reaction vials and these were stirred at the laboratory temperature (A), at the temperature of 50 °C (B), 75 °C (C) and 100 °C (D) for 48 hours. Then the reaction mixtures were analyzed using HPLC.
  • 13
  • [ 139481-44-0 ]
  • C25H22N2O5 [ No CAS ]
  • [ 147403-65-4 ]
  • 14
  • [ 139481-44-0 ]
  • [ 147404-76-0 ]
  • C25H22N2O5 [ No CAS ]
  • [ 147403-65-4 ]
  • 15
  • [ 139481-44-0 ]
  • [ 147404-76-0 ]
  • [ 147403-65-4 ]
YieldReaction ConditionsOperation in experiment
71.7% With hydroxylamine; triethylamine; In ethanol; water; for 20h;Reflux; methyl 1-[(2?-cyanobiphenyl-4-yl)methyl] -2-ethoxybenzimidazole-7-carboxylate (0.4 g, 0.97 mmol), 50percent aqueous hydroxylamine solution (1.0 g, 14.5 mmol), Triethylamine (0.1 g, 0.97 mmol) in ethanol (10 ml) was refluxed for 20 h, cooled to crystallize, and filtered to give the title compound (0.31 g, yield 71.7percent).The liquid phase data of the reaction liquid after 20 h showed that the amide impurity: product (liquid chromatographic area ratio): raw material = 7.17: 78.2: 0.
63% With hydroxylamine; triethylamine; In ethanol; water; for 24h; Raw material (compound 2A) 20 g, in the reaction bottle, adding ethanol to 200 ml, triethylamine 5 g, 50percent aqueous hydroxylamine solution 37 g, reaction 24h, the cooling crystallization, the white solid obtained 13.6 g (63.0percent). HPLC detection reaction in the reaction solution at the end of the major amide impurity (compound 6A): product is 7.15percent : 92.84percent (that is, the impurity and the product of the ratio of 1 : 12.9), see Figure 2.
With hydroxylamine; triethylamine; In ethanol; water; for 24h; Starting material (Compound 2A) 20 g, placed in a reaction flask, adding ethanol 200ml, 5 g of triethylamine, 37 g of 50percent aqueous hydroxylamine solution, the reaction 24h, cooling crystallization to give a white solid 13.6 g (63.0percent). At the end of the reaction the reaction mixture by HPLC lactam impurity was mainly (Compound. 6A): the product was 7.15percent: 92.84percent (i.e. a ratio of an impurity with the product: 12.9),
  • 16
  • [ 124-38-9 ]
  • [ 147403-65-4 ]
  • [ 147403-52-9 ]
YieldReaction ConditionsOperation in experiment
In dimethyl sulfoxide; at 90 - 100℃; under 7500.75 Torr; for 0.0166667h; 45 g (0.1 mol) of compound 2 (methyl ester) were dissolved in 450 ml of dimethylsulfoxide and separately controlled with carbon dioxideSpeed 80ml / min and flow rate 1.2L / min into the microreactor, after the temperature control unit in the reaction unit at 90-100 , PaulHold 1.0MPa pressure reaction for 60 seconds. The microreactor was obtained Azithromycin methyl ester solution by gas-liquid separator, adding 1mol / L hydrogenSodium hydroxide solution 450ml, the reaction temperature 20-30 ° C under stirring 2h, adding toluene 450ml, with hydrochloric acid to adjust the pH = 3-5,Liquid separation, after removal of toluene by adding ethanol 400ml, dissolved after cooling crystallization, and dried to give a white solid 43.6g, yield95.6percent, HPLC purity greater than 99.8percent.
 

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[ 147403-65-4 ]

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A232560 [147403-52-9]

Methyl 2-ethoxy-1-((2'-(5-oxo-2,5-dihydro-1,2,4-oxadiazol-3-yl)-[1,1'-biphenyl]-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylate

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Ethers

Chemical Structure| 147403-52-9

A232560 [147403-52-9]

Methyl 2-ethoxy-1-((2'-(5-oxo-2,5-dihydro-1,2,4-oxadiazol-3-yl)-[1,1'-biphenyl]-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylate

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Chemical Structure| 1403474-70-3

A172379 [1403474-70-3]

Ethyl 2-ethoxy-1-((2'-(5-oxo-2,5-dihydro-1,2,4-oxadiazol-3-yl)-[1,1'-biphenyl]-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylate

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Chemical Structure| 139481-44-0

A120551 [139481-44-0]

Methyl 1-((2'-cyano-[1,1'-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate

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Chemical Structure| 139481-41-7

A164996 [139481-41-7]

Ethyl 1-((2'-cyano-[1,1'-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate

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Chemical Structure| 150058-27-8

A157288 [150058-27-8]

Methyl 2-ethoxy-1H-benzo[d]imidazole-7-carboxylate

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Esters

Chemical Structure| 147403-52-9

A232560 [147403-52-9]

Methyl 2-ethoxy-1-((2'-(5-oxo-2,5-dihydro-1,2,4-oxadiazol-3-yl)-[1,1'-biphenyl]-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylate

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Chemical Structure| 1403474-70-3

A172379 [1403474-70-3]

Ethyl 2-ethoxy-1-((2'-(5-oxo-2,5-dihydro-1,2,4-oxadiazol-3-yl)-[1,1'-biphenyl]-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylate

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Chemical Structure| 139481-44-0

A120551 [139481-44-0]

Methyl 1-((2'-cyano-[1,1'-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate

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Chemical Structure| 139481-41-7

A164996 [139481-41-7]

Ethyl 1-((2'-cyano-[1,1'-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate

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Chemical Structure| 150058-27-8

A157288 [150058-27-8]

Methyl 2-ethoxy-1H-benzo[d]imidazole-7-carboxylate

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Amidines

Chemical Structure| 65695-05-8

A181383 [65695-05-8]

Methyl 4-(N-hydroxycarbamimidoyl)benzoate

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Chemical Structure| 135321-84-5

A201593 [135321-84-5]

Methyl 4-(N-(tert-butoxycarbonyl)carbamimidoyl)benzoate

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Amines

Chemical Structure| 57834-33-0

A344403 [57834-33-0]

Ethyl 4-(((methyl(phenyl)amino)methylene)amino)benzoate

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Chemical Structure| 918321-20-7

A292179 [918321-20-7]

Methyl 5-amino-4-fluoro-1-methyl-1H-benzo[d]imidazole-6-carboxylate

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Chemical Structure| 3543-73-5

A128291 [3543-73-5]

Ethyl 4-(5-amino-1-methyl-1H-benzo[d]imidazol-2-yl)butanoate

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Chemical Structure| 106429-38-3

A123328 [106429-38-3]

Methyl 2-amino-1H-benzo[d]imidazole-5-carboxylate

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Chemical Structure| 3543-74-6

A175272 [3543-74-6]

Ethyl 4-(5-(bis(2-hydroxyethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoate

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Oximes

Chemical Structure| 65695-05-8

A181383 [65695-05-8]

Methyl 4-(N-hydroxycarbamimidoyl)benzoate

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