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Chemical Structure| 147403-52-9
Chemical Structure| 147403-52-9
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Product Details of [ 147403-52-9 ]

CAS No. :147403-52-9 MDL No. :MFCD20527276
Formula : C26H22N4O5 Boiling Point : -
Linear Structure Formula :- InChI Key :PCMXVTVLQVGYLX-UHFFFAOYSA-N
M.W : 470.47 Pubchem ID :135723831
Synonyms :

Calculated chemistry of [ 147403-52-9 ]

Physicochemical Properties

Num. heavy atoms : 35
Num. arom. heavy atoms : 26
Fraction Csp3 : 0.15
Num. rotatable bonds : 8
Num. H-bond acceptors : 7.0
Num. H-bond donors : 1.0
Molar Refractivity : 129.61
TPSA : 112.24 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : Yes
CYP1A2 inhibitor : No
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : Yes
CYP2D6 inhibitor : No
CYP3A4 inhibitor : Yes
Log Kp (skin permeation) : -5.84 cm/s

Lipophilicity

Log Po/w (iLOGP) : 3.32
Log Po/w (XLOGP3) : 4.69
Log Po/w (WLOGP) : 4.28
Log Po/w (MLOGP) : 3.31
Log Po/w (SILICOS-IT) : 4.74
Consensus Log Po/w : 4.07

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -5.73
Solubility : 0.000869 mg/ml ; 0.00000185 mol/l
Class : Moderately soluble
Log S (Ali) : -6.78
Solubility : 0.000079 mg/ml ; 0.000000168 mol/l
Class : Poorly soluble
Log S (SILICOS-IT) : -8.88
Solubility : 0.000000619 mg/ml ; 0.0000000013 mol/l
Class : Poorly soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 3.0
Synthetic accessibility : 3.72

Safety of [ 147403-52-9 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 147403-52-9 ]

* 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 [ 147403-52-9 ]

[ 147403-52-9 ] Synthesis Path-Downstream   1~51

  • 1
  • [ 147403-52-9 ]
  • [ 147403-03-0 ]
YieldReaction ConditionsOperation in experiment
96.4% Example 212-Ethoxy- l -((2'-(5-oxo-4,5-dihydro-l ,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-lH- benzo[c/]imidazole-7-carboxylic acid - <strong>[147403-52-9]azilsartan</strong> of formula IIA mixture of methyl 2-ethoxy- l -((2'-(5-oxo-4,5-dihydro- l ,2,4-oxadiazol-3-yl)biphenyl-4- yl)methyl)- l H-benzo[i ]imidazole-7-carboxylate (of formula la; 4.7 g, 10 mmol), methanol (50 ml) and aqueous sodium hydroxide (2 g of NaOH in 10 ml of water) was stirred at the room temperature for 24 hours. Then, methanol was evaporated and the residue was diluted with 50 ml of water and acidified with 5percent HCl. The insolubles were aspirated and washed with water. 4.4 g (96.4 percent) of a product containing 97.8 percent of <strong>[147403-52-9]azilsartan</strong> of formula II with the melting point of 208 to 21 1 °C according to HPLC was obtained.
96.8% With sodium hydroxide; In water; at 60 - 65℃; Azilsartan methyl ester (23.5 g, 0.05 mol)plusTo 120ml quality score5percent sodium hydroxide solution,The reaction was stirred at 60-65 ° C until TLC showed complete reaction (ca. 1 h)Cooled to 0-10 ,5percent diluted hydrochloric acid to adjust the pH to 3,Suction filtration, washed with crude,Recrystallized from ethanol to give 22.1g of white crystals,Yield 96.8percent
96% With potassium hydroxide; In water; at 75℃; for 1h; In a 500 ml round-bottomed flask, compound (VII) (10 g, 21.3 mmol) and water (50 ml) were added and stirred well and added slowly.10percent potassium hydroxide solution (23.8 ml, 42.5 mmol), heated to 75 °C for 1 h,The TLC reaction is complete. Placed in an ice-water bath and lowered to 0°C, 1N hydrochloric acid was slowly added to pH=3 with stirring. The white solid of the filter cake recrystallized from absolute ethanol was 9.3 g of <strong>[147403-52-9]azilsartan</strong> (I) in a yield of 96percent.
95.6% With water; sodium hydroxide; at 20 - 30℃; for 2h; 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.
89.1% With methanol; sodium hydroxide;Reflux; A mixture of 65 g of the intermediate <strong>[147403-52-9]2-ethoxy-1-((2'-(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)benzimidazole-7-carboxylic acid methyl ester</strong>, And 620 ml of methanol were charged into a reaction flask, turn on agitation,Then, 160 g of 10percent sodium hydroxide solution was added,Rose to reflux insulation reaction,Controlled by HPLC.After completion of the reaction, the temperature was lowered to 15-25 ° C,18 g of activated carbon was added,Stirring bleaching for half an hour.Filtered, washed with 30 ml of purified water,Filtration to dry, dropping hydrochloric acid,Adjust the pH to 2 to 3, adjust the mixing 1h, filter, with 30ml of purified water washing, filter to dry to get crude. The crude product was added to 200 ml of methanol, stirring, heating reflux 1h, cooling to 0 ~ 5 , stirring 1h, suction filtration,Washed with 20 ml of methanol, suction filtered to dryness,At 60 ~ 70 ° C to dry to dry azithentin into 56.1 g, yield 89.1percent, purity 99.6percent.
88.7% With methanol; sodium hydroxide; at 20℃; for 10h; Into a 500 ml round bottom flask, 10 g of a raw material A4, 110 ml of methanol was added, and 28.8 ml of a 10percent NaOH solution was added under stirring at room temperature, and the reaction was stirred for 10 hours. After the reaction was completed, the methanol was spun dry. And adding 200 ml of water to the system, and adjusting the pH to 3-4 with HCl (1 mol/L), At this point a large amount of white solids are produced, suction filtration, Obtain crude product, separate and purify by column chromatography. Dichloromethane: methanol (1:20) gave 8.6 g of a white solid, yield 88.7percent, purity 97.4percent.
88% With pyrographite; potassium hydroxide; In water; at 50℃; for 1h; 20 g of compound II-1 was added to a 5percent aqueous KOH solution.Stir the mixture to 50 ° C for 1 h, add activated carbon and continue to stir.Filter and collect the filtrate. Cool down to 10 ° C, adjust pH to 1 with hydrochloric acidFiltration, washing and drying to obtain Compound I, the yield is 88percent
77.4% With sodium hydroxide; at 73 - 75℃; for 2h; Compound (5A) 2.0 g, placed in a reaction flask, 0.4mol / L sodium hydroxide, 32ml, 73-75 reaction for 2 hours.After the reaction was cooled to room temperature, a solution of aqueous acid solution to pH = 3-4, the precipitated white solid 1.5g, 77.4percent.
75% Example 3Preparation of l-[[2'-(4, 5-dihydro-5-oxo-4H-l, 2, 4-oxadiazol-3-yl) biphenyl-4-yl] methyl]-2-ethoxy-lH-benzimidazoIe-7-carboxylic Acid (Azilsartan)Methyl l-[[2'-(4,5-dihydro-5-oxo-4H-l,2,4-oxadiazol-3-yl) biphenyl-4-yl] methyl]-2-ethoxy-lH-benzimidazole-7-carboxylate (30 g) and NaOH solution (0.4 N; 475 ml) was stirred at 50-55°C for 30 min. Reaction mass was cool to 10-15°C and water was added. The pH of the resulting solution was adjusted to 2-3 by using 2 N HC1. Reaction mass was stirred for 30 mins. at 20-25°C. The product was filtered and dried under vacuum. The resulting product was suspended in isopropyl alcohol and was stirred for 25-30 mins. at 40-45°C. The product was filtered, washed and dried to obtain title compound. (Yield: 22 g; 75percent)
Example 11 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-carboxylic acid - <strong>[147403-52-9]azilsartan</strong> of formula IIA mixture of ethyl 2-ethoxy-l-((2'-(5-oxo-4,5-dihydro-l ,2,4-oxadiazol-3-yl)biphenyl-4- yl)methyl)-l H-benzo[< ]imidazole-7-carboxylate (of formula la; 3.2 g, 6.6 mmol) and aqueous sodium hydroxide (0.8 g of NaOH in 50 ml of water) was stirred at the temperature of 70°C for 1.5 hours. After cooling to the room temperature the mixture was acidified with 10percent HCl until pH 3 while being stirred and cooled. The insolubles were aspirated and washed with water. 2.6 g (86.2 percent) of a product was obtained containing 97.2 percent of <strong>[147403-52-9]azilsartan</strong> of formula II with the melting point of 208 to 21 1 °C according to HPLC. NMR spectrum: NMR (500 MHz, DMSO) delta (ppm): 13.17 (bs, 1H, OH or NH), 12.42 (bs, 1H, OH or NH), 7.70-7.60 (m, 3H, Ar), 7.57-7.50 (m, 2H, Ar), 7.50-7.44 (m, 1 H, Ar), 7.23 (d, J = 8.3 Hz, 2H, Ar), 7.18 (t, J = 7.9 Hz, lH, Ar), 7.05 (d, J = 8.3 Hz, 2H, Ar), 5.68 (s, 2H, N-CH2-Ar), 4.58 (q, J = 7.1 Hz, 2H, OCH2CH3), 1.38 (t, J = 7.1 Hz, 3H, OCH2CH3).
With lithium hydroxide; In water; at 20℃; for 16h; 10 g of the <strong>[147403-52-9]azilsartan</strong> intermediate compound I crystal obtained in this example dispersed in 45 mL of water. Then, 5.0 mL of lithium hydroxide aqueous solution with a solute mass fraction of 20percent was added. After stirring at room temperature for 16 hours, the aqueous solution was acidified with dilute hydrochloric acid to rhoH- = 3. Filtration and ethanol recrystallization gave <strong>[147403-52-9]azilsartan</strong> product with a purity of 99percent.
82.5 g With lithium hydroxide; In methanol; water; for 3h;Reflux; placed <strong>[147403-52-9]<strong>[147403-52-9]azilsartan</strong> methyl ester</strong> 100 g, methanol 730mL to 5000mL four-neck flask equipped with two stirring blades with a diameter of 15cm, was dissolved by heating with stirring.Was added thereto 2N aqueous lithium 590mL hydroxide, was heated to reflux temperature, the reaction was conducted for 3 hours.The resulting reaction solution was cooled to room temperature to prepare a pH of the reaction solution with 2N aqueous hydrochloric acid solution 3.And concentrating the reaction solution, the resulting residue in water 1200 mL, stirred with dichloromethane 3000 mL 30 minutes, allowed to stand for 15 minutes, was fractionated and the dichloromethane layer by a liquid.The resulting dichloromethane solution was concentrated to the resulting residue was stirred overnight at 20 to 30 ° C. was added ethyl acetate 2000 mL.Then, a sample was collected under reduced pressure filtered and precipitated crystals were dried at 50 ° C., to give colorless prisms of <strong>[147403-52-9]azilsartan</strong> of 82.5 g (<strong>[147403-52-9]azilsartan</strong> purity: 96.12percent).

  • 2
  • C34H40N4O6 [ No CAS ]
  • [ 147403-52-9 ]
  • 5
  • 0.36N-NaOH [ No CAS ]
  • [ 7440-44-0 ]
  • [ 147403-52-9 ]
  • [ 147403-03-0 ]
YieldReaction ConditionsOperation in experiment
96% Reference Example 5 To methyl 2-ethoxy-1-[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylate (10 g) was added 0.36N-NaOH (150 mL) and the mixture was stirred at 65-75°C for 1.5 hr. The mixture was adjusted to pH 8 at room temperature with 1N HCl, activated carbon (0.5 g) was added and the mixture was stirred. The activated carbon was filtered off and the residue was washed with water (50 mL). The mixture was adjusted to pH 3 with 0.5N HCl at 9-15°C. The mixture was stirred at 40-45°C and then at 5-15°C. The precipitated crystals were collected by filtration, washed with water (20 mL), and dried at 40°C to give compound A as a white powder (9.3 g, yield 96percent).
  • 6
  • 0.40N-NaOH [ No CAS ]
  • [ 7440-44-0 ]
  • [ 147403-52-9 ]
  • [ 147403-03-0 ]
YieldReaction ConditionsOperation in experiment
96% Reference Example 4 To methyl 2-ethoxy-1-[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylate (10 g) was added 0.40N-NaOH (167 mL) and the mixture was stirred at 65-75°C for 1-1.5 hr. The mixture was adjusted to pH 8 at room temperature with 1N HCl, activated carbon (0.5 g) was added and the mixture was stirred. The activated carbon was filtered off and the residue was washed with water (17 mL). The mixture was adjusted to pH 3 with 1N HCl at 0-5°C. The mixture was stirred at 40-45°C and then at 0-10°C. The precipitated crystals were collected by filtration, washed with water (17 mLx2 times), and dried at 40°C to give compound A as a white powder (9.3 g, yield 96percent).
  • 7
  • [ 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)
  • 9
  • [ 147403-52-9 ]
  • 1-[{2’-(2,5-dihydro-5-oxo-1,2,4-oxodiazol-3-yl)(1,1’-biphenyl)-4-yl}methyl]-2-ethoxy-1H-benzimidazole-7-carboxylic acid (5-methyl-2-oxo-1,3-dioxol-4-yl) methyl ester potassium salt [ No CAS ]
  • 11
  • C34H40N4O6 [ No CAS ]
  • [ 1403474-78-1 ]
  • [ 147403-52-9 ]
YieldReaction ConditionsOperation in experiment
In xylene; for 2h;Reflux; A mixture of the evaporation residue and xylene (15 ml) was heated to reflux for 2 hours. The evaporation provided 0.9 g of an evaporation residue containing 0.9percent of the intermediate (VI; R' = 2-ethylhexyl), 64.0 percent of the product of formula la and 5.2 percent of the product of formula Vila according to HPLC. The total content of the product of formula la corresponds to a yield of 64 percent.The evaporation residue was dissolved in a mixture of CHC13 (3 ml) and ethyl acetate (1 ml); an insoluble product started to separate after a short time. The mixture was left to stand at the room temperature; then the insolubles were aspirated. 0.55 g of ochre crystals was obtained containing 90.4percent of the product of formula la and 8.6 percent of formula Vila according to HPLC. The total content of the product of formula la corresponds to a yield of 40 percent.
In xylene; for 2h;Reflux; Example 3 Methyl 2-ethoxy-l -((2'-(5-oxo-4,5-dihydro- l ,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-lH- benzo[<f]imidazole-7-carboxylate of formula la - reproduction of the procedure (J. Med. Chem. 1996, 59(26), 5228-5235)2-ethylhexyl chloroformate (0.25 g, 2.6 mmol) was added to a stirred mixture of methyl 2- ethoxy- 1 -((2'-((hydroxyamino)iminomethyl)biphenyl-4-yl)methyl)- 1 H-benzo [d] imidazole-7- carboxylate (of formula Va; 1 .16 g, 2.6 mmol), dry DMF (5 ml) and pyridine (0.22 g) under cooling in a water-ice mixture and the mixture was stirred at the temperature of 0°C for 30 minutes. After dilution with water (20 ml) the mixture was extracted with ethyl acetate (4 x 10 ml), the extract was washed with water (4 x 5 ml) and dried with MgSC The obtained evaporation residue ( 1 .7 g) contained 92.2 percent of the intermediate (of formula VI; R' = 2- ethylhexyl) according to HPLC. A mixture of the evaporation residue and xylene (15 ml) was heated to reflux for 2 hours. The evaporation provided 0.9 g of an evaporation residue containing 0.9percent of the intermediate (VI; R' = 2-ethylhexyl), 64.0 percent of the product of formula la and 5.2 percent of the product of formula Vila according to HPLC. The total content of the product of formula la corresponds to a yield of 64 percent.The evaporation residue was dissolved in a mixture of CHCI3 (3 ml) and ethyl acetate (1 ml); an insoluble product started to separate after a short time. The mixture was left to stand at the room temperature; then the insolubles were aspirated. 0.55 g of ochre crystals was obtained containing 90.4percent of the product of formula la and 8.6 percent of formula Vila according to HPLC. The total content of the product of formula la corresponds to a yield of 40 percent.
  • 12
  • [ 1403477-45-1 ]
  • [ 147403-03-0 ]
  • [ 147403-52-9 ]
YieldReaction ConditionsOperation in experiment
11.3%Chromat.; 72.7%Chromat. With sodium methylate; In 1-methyl-pyrrolidin-2-one; at 20℃; for 4h; Example 4 Methyl 2-ethoxy- 1 -((2'-(5-oxo-4,5-dihydro- 1 ,2,4-oxadiazol-3 -yl)biphenyl-4-yl)methyl)- 1 H- benzo[<i]imidazole-7-carboxylate of formula la0.05 g of the corresponding base was added to a mixture of 0.2 g of methyl 2-ethoxy- 1 -((2'- (A^-(methoxycarbonyloxy)carbamimidoyl)biphenyl-4-yl)methyl)-lH-benz[if]imidazole-7- carboxylate (of formula Vlaa; R' = Me) and 4 ml of the respective solvent, stirred in a reaction vial, and the mixture was stirred at the room temperature for 4 h. The collected samples were acidified with acetic acid and analyzed with HPLC. The results are summarized in Table I. Table I - Yield and purity of the product of Example 4
77.9%Chromat.; 17.1%Chromat. With sodium methylate; In dimethyl sulfoxide; at 20℃; for 4h; Example 4 Methyl 2-ethoxy- 1 -((2'-(5-oxo-4,5-dihydro- 1 ,2,4-oxadiazol-3 -yl)biphenyl-4-yl)methyl)- 1 H- benzo[<i]imidazole-7-carboxylate of formula la0.05 g of the corresponding base was added to a mixture of 0.2 g of methyl 2-ethoxy- 1 -((2'- (A^-(methoxycarbonyloxy)carbamimidoyl)biphenyl-4-yl)methyl)-lH-benz[if]imidazole-7- carboxylate (of formula Vlaa; R' = Me) and 4 ml of the respective solvent, stirred in a reaction vial, and the mixture was stirred at the room temperature for 4 h. The collected samples were acidified with acetic acid and analyzed with HPLC. The results are summarized in Table I. Table I - Yield and purity of the product of Example 4
  • 13
  • [ 1403477-45-1 ]
  • [ 147403-52-9 ]
YieldReaction ConditionsOperation in experiment
96.1%Chromat. With 1,8-diazabicyclo[5.4.0]undec-7-ene; In dimethyl sulfoxide; at 20℃; for 4h;Product distribution / selectivity; Example 4 Methyl 2-ethoxy- 1 -((2'-(5-oxo-4,5-dihydro- 1 ,2,4-oxadiazol-3 -yl)biphenyl-4-yl)methyl)- 1 H- benzo[<i]imidazole-7-carboxylate of formula la0.05 g of the corresponding base was added to a mixture of 0.2 g of methyl 2-ethoxy- 1 -((2'- (A^-(methoxycarbonyloxy)carbamimidoyl)biphenyl-4-yl)methyl)-lH-benz[if]imidazole-7- carboxylate (of formula Vlaa; R' = Me) and 4 ml of the respective solvent, stirred in a reaction vial, and the mixture was stirred at the room temperature for 4 h. The collected samples were acidified with acetic acid and analyzed with HPLC. The results are summarized in Table I. Table I - Yield and purity of the product of Example 4
  • 14
  • [ 1403477-45-1 ]
  • [ 1403474-78-1 ]
  • [ 147403-52-9 ]
  • 15
  • [ 1403477-44-0 ]
  • [ 147403-52-9 ]
YieldReaction ConditionsOperation in experiment
94.6% With potassium carbonate; In 1-methyl-pyrrolidin-2-one; at 20℃; for 1h; Example 8Methyl 2-ethoxy- l -((2'-(5-oxo-4,5-dihydro- l ,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)- l H- benzo[c ]imidazole-7-carboxylate of formula laK2CO3 (0.5 g, 3.6 mmol) was added to a mixture of 1.8 g (3.2 mmol) of methyl 2-ethoxy- 1 - ((2'-(N'-(phenyloxycarbonyloxy)-carbamimidoyl)biphenyl-4-yl)methyl)- 1 H-benzftf]- imidazole-7-carboxylate (of formula Viae; R' = Ph) and 15 ml of NMP and the mixture was stirred at the room temperature for 1 h. The reaction mixture contained 90.2percent of the compound of formula la and 4.2 percent of the starting compound according to HPLC (a mixture containing 96.4 percent of the compound of the corresponding formula Viae according to HPLC. After stirring for another hour the reaction mixture was poured into water (75 ml) and the resulting solution was acidified with acetic acid. 1 .42 g (94.6 percent) was obtained containing 100.0 percent of a product of formula la according to HPLC.
  • 16
  • [ 147404-82-8 ]
  • [ 147403-52-9 ]
YieldReaction ConditionsOperation in experiment
94.3% With potassium carbonate; In dimethyl sulfoxide; at 20℃; for 3h; Example 7Methyl 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 laUsing the procedure described in Example 6 methyl 2-ethoxy- 1 -((2'-(7V-(ethoxycarbonyloxy)- carbamimidoyl)biphenyl-4-yl)methyl)- l H-benz[ci]imidazole-7-carboxylate (of formula Vlab; R' = Et) was converted to methyl 2-ethoxy- l -((2'-(5-oxo-4, 5-dihydro- l , 2,4-oxadiazol-3- yl)biphenyl-4-yl)methyl)- l H-benzo[i ]imidazole-7-carboxylate of formula la. 94.3percent of a substance containing 96.3percento of the product of formula la according to HPLC was obtained.
In toluene; at 100℃; Add 30 g of ethyl acetate, 15 g of compound III-1, 3 g of trimethylamine to the reaction flask, stir, and cool to 5 ° C.Slowly add 5.1g isopropyl chloroformate,After the addition, the reaction continues at this temperature.After the reaction is completed, water is added to quench it.The aqueous layer was washed once with ethyl acetate.The ethyl acetate solution was combined and the ethyl acetate layer was washed once with water.Concentration under reduced pressure gave a solid V-1. The obtained solid V-1 and toluene were added to the reaction flask.Stirring to 100 ° C, the reaction is completed,The crystal was cooled and crystallized, and the crude compound II-1 was obtained by filtration.The obtained crude product of II-1 was added to toluene, and stirred and crystallized at 50 ° C for 1 h.The mixture was cooled to 10 ° C and stirred for 1 h, and filtered to obtain compound II-1.The yield was 77percent.
  • 17
  • [ 147404-82-8 ]
  • [ 1403474-78-1 ]
  • [ 147403-52-9 ]
YieldReaction ConditionsOperation in experiment
In xylene; for 1.5h;Reflux; A mixture of the evaporation residue and xylene (10 ml) was heated up to reflux for 1.5 hours. Ethyl acetate (25 ml) was added to the partially cooled reaction mixture; the solution was washed with water (2 x 10 ml) and then dried with MgS04. 0.9 g of an evaporation residue was obtained, containing 2.2 percent of the intermediate (VI; R' = Et), 47.5 percent of the product of formula la and 1 5.8 percent of the compound of formula Vila according to HPLC. The total content of the product of formula la corresponds to a yield of 46 percent.
In xylene; for 1.5h;Reflux; Example 1Methyl 2-ethoxy- l -((2'-(5-oxo-4,5-dihydro-l ,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)- lH- benzo[d]imidazole-7-carboxylate of formula la - reproduction of the procedure (US5,583, 141 ; EP 0 520 423).A solution of ethyl choroformate (0.22 g, 2 mmol) in dichloromethane (2 ml) was added dropwise to a stirred mixture of methyl 2-ethoxy-l -((2'-((hydroxyamino)iminomethyl)- biphenyl-4-yl)methyl)- l H-benzo[ii]imidazole-7-carboxylate of formula Va; 0.89 g, 2 mmol), dry THF (30 ml) and triethylamine (0.2 g) under cooling in a water-ice mixture and the mixture was stirred at the room temperature for 2 hours. The insolubles were aspirated and the filtrate was evaporated to dryness; the evaporation residue was diluted with ethyl acetate (5 ml), the insolubles were aspirated and the filtrate was evaporated again. The evaporation residue (1.0 g) contained 98.2percent of the intermediate (of formula Vlab; R' = Et) according to HPLC.A mixture of the evaporation residue and xylene (10 ml) was heated up to reflux for 1.5 hours. Ethyl acetate (25 ml) was added to the partially cooled reaction mixture; the solution was washed with water (2 10 ml) and then dried with MgSC>4. 0.9 g of an evaporation residue was obtained, containing 2.2 percent of the intermediate (VI; R' = Et), 47.5 percent of the product of formula la and 15.8 percent of the compound of formula Vila according to HPLC. The total content of the product of formula la corresponds to a yield of 46 percent.
  • 18
  • [ 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.
  • 19
  • [ 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
  • 20
  • [ 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.
  • 21
  • [ 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.
  • 22
  • [ 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
  • 23
  • [ 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.
  • 24
  • [ 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
  • 25
  • [ 139481-41-7 ]
  • [ 147403-52-9 ]
  • 26
  • [ 1397836-41-7 ]
  • [ 124-41-4 ]
  • [ 616-38-6 ]
  • [ 147403-52-9 ]
  • 27
  • [ 147403-52-9 ]
  • [ 1417576-00-1 ]
  • 28
  • [ 147403-52-9 ]
  • [ 1417576-01-2 ]
  • 29
  • [ 147403-52-9 ]
  • [ 1403474-78-1 ]
  • 30
  • [ 75-03-6 ]
  • [ 147403-52-9 ]
  • [ 1499167-76-8 ]
  • 32
  • (Z)-4'-(bromomethyl)-N'-hydroxy-[1,1'-biphenyl]-2-carboxamidine [ No CAS ]
  • [ 147403-52-9 ]
  • 33
  • (Z)-4'-(bromomethyl)-N'-((ethoxycarbonyl)oxy)-[1,1'-biphenyl]-2-carboxamidine [ No CAS ]
  • [ 147403-52-9 ]
  • 34
  • [ 150058-27-8 ]
  • 3-(4'-(bromomethyl)-[1,1'-biphenyl]-2-yl)-1,2,4-oxadiazol-5(4H)-one [ No CAS ]
  • [ 147403-52-9 ]
YieldReaction ConditionsOperation in experiment
78% With tetrabutylammomium bromide; potassium carbonate; In ethanol; at 20℃; for 10h;Reflux; 60 g of 2-ethoxy-1H-benzimidazole-7-carboxylic acid methyl ester and 500 ml of ethanol were added to the clean reaction flask, Stirred at room temperature for 10 minutes, 75.5 g of potassium carbonate was added, 60.3g 3-(4'-(bromomethyl)-[1,1'-biphenyl]-2-yl)-1,2,4-oxadiazol-5(4H)-one , and 4.8 g of tetrabutylammonium bromide, heated to reflux 10h, the ethanol was evaporated to dryness under reduced pressure, and the mixture was stirred for half an hour in 1800 ml of water, 120ml water washing, filter to dry, solid with 400ml ethanol temperature reflux solution dissolved, cooling to 0-5 , 2 hours of crystallization temperature.Filtered, washed with 20 ml of ethanol, suction filtered to dryness, in 50 to 60 vacuum drying, 2-ethoxy-1-((2'-(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)benzimidazole-7-carboxylic acid methyl ester was obtained 66.8 g, yield: 78.0percent, purity: 98.9percent)
  • 35
  • [ 114772-54-2 ]
  • [ 147403-52-9 ]
  • 36
  • [ 147404-82-8 ]
  • [ 147403-52-9 ]
YieldReaction ConditionsOperation in experiment
80.3% In ethanol; for 22h;Reflux; Compound (4A, R = methyl) 3.59 g, placed in a reaction flask, 45ml of ethanol was refluxed for 22 hours, cooling crystallization to give a solid 2.7 g, yield 80.3percent.
80.3% In ethanol; for 22h;Reflux; The compound (4A, R = methyl) 3. 59 grams, placed in the reaction flask, adding ethanol 45ml reflux 22 hours, cooling crystallization of solid 2. 7 grams, yield 80. 3percent
  • 37
  • [ 139481-44-0 ]
  • [ 530-62-1 ]
  • [ 147403-52-9 ]
YieldReaction ConditionsOperation in experiment
96.7% Hydroxylamine hydrochloride (33.4 g, 0.48 mol),DBU (109.5 g, 0.72 mol) plusTo 190ml dioxane at room temperature for 30min,JoinMethyl 2-ethoxy-1- (2'-cyanobiphenyl-4-yl) methylbenzimidazole-7-carboxylate(32.9 g, 0.08 mol),The reaction was stirred at 80-85 ° C until TLC showed complete reaction (about 11h)After cooling to room temperature N'N-carbonyldiimidazole (13.0 g, 0.08 mol)Stirring 1h,The solvent was evaporated under reduced pressure, water 160ml,Stirring 8percent diluted hydrochloric acid to adjust the pH to 4,Suction filtration, washed with water, washed with dichloromethane, dried to give a white powder 36.4g, a yield of 96.7percent.
  • 38
  • [ 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.
  • 39
  • [ 147403-52-9 ]
  • C25H19N4O5(1-)*Na(1+) [ No CAS ]
YieldReaction ConditionsOperation in experiment
47.4 g With water; sodium hydroxide; In N,N-dimethyl-formamide; at 5 - 15℃; for 0.1h; 235 ml of DMF was added to the reaction flask, cooled to 5 ° C with stirring in an ice bath and 12 g of sodium hydroxide(0.3 mol, formulated as a 50percent aqueous solution) of sodium hydroxide in water and 47 g of the compound of formula I (0.1 mol) were added, dissolved with stirring,The reaction was continued until the temperature reached 15 ° C. After about 1 h, the reaction was completed by TLC (developing solvent petroleum ether: ethyl acetate: acetic acid = 3: 2: 0.25).Filtration and filtration of the cake with 235 ml of acetone gave the compound of formula II as a white solid, as a sodium salt, after drying to a weight of 47.4 g
  • 40
  • [ 147403-52-9 ]
  • C25H19N4O5(1-)*K(1+) [ No CAS ]
YieldReaction ConditionsOperation in experiment
With water; potassium hydroxide; In N,N-dimethyl-formamide; at 5 - 15℃; for 0.1h; The reaction flask was added 235ml DMF, ice-cooled with stirring to 5 ° C, was added potassium hydroxide 16.8 g(0.3 mol, formulated as a 50percent aqueous solution) of potassium hydroxide, 47 g of the compound of formula I (0.1 mol) was added, and the mixture was stirred to dissolveThe reaction was continued until the temperature reached 15 ° C. After about 1 h, the reaction was completed by TLC (developing solvent petroleum ether: ethyl acetate: acetic acid = 3: 2: 0.25).Filtration and washing of the filter cake with 235 ml of acetone gave the compound of formula II as a white solid, as the potassium salt.
  • 41
  • [ 147403-52-9 ]
  • C25H19N4O5(1-)*Li(1+) [ No CAS ]
YieldReaction ConditionsOperation in experiment
With water; lithium hydroxide; In N,N-dimethyl-formamide; at 5 - 15℃; for 0.1h; 235 ml of DMF was added to the reaction flask, cooled to 5 ° C with stirring in an ice bath, and 7.2 g of lithium hydroxide(0.3 mol, formulated as a 50percent aqueous solution) of lithium hydroxide in water, 47 g of the compound of formula I (0.1 mol) was added, and the mixture was stirred to dissolveThe reaction was continued until the temperature reached 15 ° C. After about 1 h, the reaction was completed by TLC (developing solvent petroleum ether: ethyl acetate: acetic acid = 3: 2: 0.25).Filtration and filtration of the cake with 235 ml of acetone gave the compound of formula II as a white solid as a lithium salt
  • 42
  • C25H22ClN3O4 [ No CAS ]
  • [ 67-64-1 ]
  • [ 147403-52-9 ]
YieldReaction ConditionsOperation in experiment
81% With potassium cyanate; at 20℃; for 12h; A 500 ml round bottom flask was added with 1-[(2'-chloro(formylhydrazino)biphenyl-4-yl)methyl]-2-ethoxybenzimidazole-7-carboxylic acid methyl ester (VI) (15.0 g, 32.3 mmol), potassium cyanate (3.9 g, 48.5 mmol) and anhydrous acetone (100 ml) were stirred at room temperature for 12 h.TLC detection reaction is complete. The reaction solution was poured into 200 ml of water, and a large amount of solids precipitated, which was filtered with suction and washed with a small amount of water to obtain 12.3 g of a white solid product with a yield of 81percent.
  • 43
  • [ 150058-27-8 ]
  • [ 147403-52-9 ]
  • 44
  • [ 911314-60-8 ]
  • [ 147403-52-9 ]
  • 45
  • methyl 1-[(2'-formylbiphenyl-4-yl)methyl]-2-ethoxybenzimidazole-7-carboxylate [ No CAS ]
  • [ 147403-52-9 ]
  • 46
  • C25H23N3O4 [ No CAS ]
  • [ 147403-52-9 ]
  • 47
  • [ 147403-52-9 ]
  • C35H28N4O11 [ No CAS ]
  • 48
  • [ 80841-78-7 ]
  • [ 147403-52-9 ]
  • C31H26N4O8 [ No CAS ]
YieldReaction ConditionsOperation in experiment
77.5% In a 250 ml round bottom flask, 5 g of <strong>[147403-52-9]<strong>[147403-52-9]azilsartan</strong> methyl ester</strong> intermediate A4, potassium carbonate 2.2 g, potassium iodide 0.15 g, DMSO 70 mL, cooled to -10 to 0 ° C and stirred for 1 hour. A solution of 1.9 g of 4-chloromethyl-5-methyl-1,3-dioxol-2-one in 30 mL of DMSO was added dropwise to the above reaction system. After the addition is completed, the reaction is allowed to rise to room temperature for 2 to 4 hours. After the reaction was completed, 200 mL of water was added, and the pH was adjusted to 2 to 3 with dilute hydrochloric acid, and filtered, and the residue was washed three times with water and then dried. The crude product was purified by silica gel column chromatography. The eluent was dichloromethane-methanol (DCM: MeOH = 50:1). The product was obtained in an amount of 4.8 g, a yield of 77.5percent, and a purity of 96.2percent.
  • 49
  • [ 80715-22-6 ]
  • [ 147403-52-9 ]
  • C31H26N4O8 [ No CAS ]
YieldReaction ConditionsOperation in experiment
77.5% Into a 250 ml round bottom flask, 5 g of <strong>[147403-52-9]<strong>[147403-52-9]azilsartan</strong> methyl ester</strong> intermediate A4, potassium carbonate 2.2 g, and DMF 70 mL were placed, and the mixture was cooled to -10 to 0 ° C and stirred for 0.5 hour. 2.1 g of 4-bromomethyl-5-methyl-1,3-dioxol-2-one in 30 mL of DMF was added dropwise to the above reaction system. After the addition is completed, the reaction is allowed to rise to room temperature for 2 to 4 hours. After the reaction was completed, 200 mL of water was added, and the pH was adjusted to 2 to 3 with dilute hydrochloric acid, and filtered, and the residue was washed three times with water and then dried.The crude product was purified by silica gel column chromatography.The eluent was dichloromethane-methanol (DCM: MeOH = 50:1).The product was obtained in an amount of 4.8 g, a yield of 77.5percent, and a purity of 97.1percent.
  • 50
  • [ 80841-79-8 ]
  • [ 147403-52-9 ]
  • C31H26N4O8 [ No CAS ]
YieldReaction ConditionsOperation in experiment
79.1% Add 5g of <strong>[147403-52-9]<strong>[147403-52-9]azilsartan</strong> methyl ester</strong> intermediate A4 to a 250ml round bottom flask. Potassium carbonate 3.0g, potassium iodide 0.4g, DMF 70mL, Cool to -10 to 0 ° C and stir for 0.5 hours. A solution of 1.9 g of 4-iodomethyl-5-methyl-1,3-dioxol-2-one in 30 mL of DMF was added dropwise to the above reaction system, and after heating, the temperature was raised to 40 ° C to react 2 to 4 hour. After the reaction is completed, add 200 mL of water. The pH was adjusted to 2 to 3 with dilute hydrochloric acid, filtered, and the residue was washed three times with water and dried. The crude product was purified by silica gel column chromatography. The eluent was dichloromethane-methanol (DCM: MeOH = 50:1). The product was obtained in an amount of 4.9 g, a yield of 79.1percent, and a purity of 96.4percent.
  • 51
  • [ 139481-28-0 ]
  • [ 147403-52-9 ]
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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| 866084-31-3

[ 866084-31-3 ]

tert-Butyl 4-(6-((6-(1-butoxyvinyl)-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazine-1-carboxylate

Similarity: 0.55

Chemical Structure| 1377049-84-7

[ 1377049-84-7 ]

Methyl ((2S)-1-((2S,5S)-2-(9-(2-((2S,4S)-1-((2R)-2-((methoxycarbonyl)amino)-2-phenylacetyl)-4-(methoxymethyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)-1,11-dihydroisochromeno[4',3':6,7]naphtho[1,2-d]imidazol-2-yl)-5-methylpyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)carbamate

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Chemical Structure| 211915-84-3

[ 211915-84-3 ]

Ethyl 3-(2-(((4-cyanophenyl)amino)methyl)-1-methyl-N-(pyridin-2-yl)-1H-benzo[d]imidazole-5-carboxamido)propanoate

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Esters

Chemical Structure| 1403474-70-3

[ 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| 147403-65-4

[ 147403-65-4 ]

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

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Chemical Structure| 139481-44-0

[ 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

[ 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| 139481-69-9

[ 139481-69-9 ]

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

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Related Parent Nucleus of
[ 147403-52-9 ]

Oxadiazoles

Chemical Structure| 1403474-70-3

[ 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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Benzimidazoles

Chemical Structure| 1403474-70-3

[ 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| 147403-65-4

[ 147403-65-4 ]

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

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Chemical Structure| 139481-44-0

[ 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

[ 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| 139481-72-4

[ 139481-72-4 ]

2-Ethoxy-1-((2'-(1-trityl-1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylic acid

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