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HazMat fee for 500 gram (Estimated)
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USD 80+
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Structure of 139481-69-9 * Storage: {[proInfo.prStorage]}
* 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.
Stage #1: With sodium azide; tributyltin chloride In toluene at 110 - 115℃; for 24 h; Heating / reflux Stage #2: With acetic acid In methanol; water; toluene at 15 - 20℃; for 1 h;
Preparation of 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]- lH-benzimidazole-7-carboxylic acid methyl ester To 2-ethoxy-1-[[2'-cyano [l, 1'-biphenyl] -4-yl] methyl]-lH-benzimidazole-7- carboxylic acid methyl ester of Formula IV (310 g) in toluene (2.48 L) added tributyltin chloride (737 g) and sodium azide (146 g) and tetrabutyl ammonium bromide (31 g). The resultant mass was slowly heated to 110°C and maintained for 24 hours at 110-115°C. The reaction was monitored by TLC and after completion of reaction, the reaction mass was cooled to 15°C. Added methanol (3.1 L) and water (2.17 L) to the reaction mass followed by addition of acetic acid (930 g). The resultant mixture was stirred at 15-20°C for 1 hour to allow separation of the product. Charged toluene (1.24 L) at 15-20°C and filtered the reaction mass. Washed the cake thoroughly with water (0.93 L) to completely remove the acidity (until the pH of the washing is between about 5.5 to about 7.0). Washed the cake with toluene (0.62 L) and suck dried. Air dried the product at 50-55°C to afford the title compound. Yield: 290 g (85percent)
With sodium nitrite In ethanol; hexane; ethyl acetate; toluene
EXAMPLE 5 Methyl 2-ethoxy-1-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methylbenzimidazole-7-carboxylate A mixture of 13.0 g of methyl 1-(2'-cyanobiphenyl-4-yl)methyl-2-ethoxybenzimidazole-7-carboxylate, 47.1 g of trioctyltin azide (tri-n-octyltin azide) and 60 ml of toluene was refluxed at 125° C. for 31 hours. After cooling, the reaction mixture was concentrated. To the concentrate was added 56 ml of ethanol as well as an aqueous solution of sodium nitrite (7.7 g/28 ml) and the mixture was adjusted to pH 5 with concentrated hydrochloric acid. Then, 31 ml of ethyl acetate was added. The mixture was further adjusted to pH 1.1 with concentrated hydrochloric acid, diluted with 20 ml of n-hexane and adjusted to pH 3.3 with 1N aqueous sodium hydroxide solution. The crystals were separated, washed with ethyl acetate/n-hexane mixture (1:3) and dried to provide 14.56 g of methyl 2-ethoxy-1-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methylbenzimidazole-7carboxylate. Yield 100percent. 1 H NMR (CDCl3) δ: 1.42 (3H, t), 3.56 (3H, s), 4.27 (2H, q), 5.54 (2H, s), 6.70 (2H, d), 6.78-6.95 (4H, m), 7.28-7.33 (1H, m), 7.40 (1H, dd), 7.56-7.66 (2H, m), 8.02-8.06 (1H, m) IR(KBr): 1720, 1618, 1548, 1476, 1432, 1390, 1354, 1324, 1284, 1222, 1134, 1042, 872, 840, 820, 780, 756 cm-1.
Reference：
[1] Patent: US5484955, 1996, A,
3
[ 21606-04-2 ]
[ 139481-69-9 ]
Reference：
[1] Journal of Medicinal Chemistry, 1993, vol. 36, # 15, p. 2182 - 2195
[2] Patent: WO2011/145100, 2011, A1,
4
[ 73833-13-3 ]
[ 139481-69-9 ]
Reference：
[1] Journal of Medicinal Chemistry, 1993, vol. 36, # 15, p. 2182 - 2195
[2] Patent: WO2011/145100, 2011, A1,
5
[ 603-11-2 ]
[ 139481-69-9 ]
Reference：
[1] Journal of Medicinal Chemistry, 1993, vol. 36, # 15, p. 2182 - 2195
[2] Patent: WO2011/145100, 2011, A1,
6
[ 57113-90-3 ]
[ 139481-69-9 ]
Reference：
[1] Journal of Medicinal Chemistry, 1993, vol. 36, # 15, p. 2182 - 2195
[2] Patent: WO2011/145100, 2011, A1,
7
[ 136304-78-4 ]
[ 139481-69-9 ]
Reference：
[1] Journal of Medicinal Chemistry, 1993, vol. 36, # 15, p. 2182 - 2195
[2] Patent: WO2011/145100, 2011, A1,
8
[ 139481-28-0 ]
[ 139481-69-9 ]
Reference：
[1] Journal of Medicinal Chemistry, 1993, vol. 36, # 15, p. 2182 - 2195
[2] Patent: WO2011/145100, 2011, A1,
9
[ 856414-36-3 ]
[ 139481-69-9 ]
Reference：
[1] Journal of Medicinal Chemistry, 1993, vol. 36, # 15, p. 2182 - 2195
10
[ 139481-38-2 ]
[ 139481-69-9 ]
Reference：
[1] Journal of Medicinal Chemistry, 1993, vol. 36, # 15, p. 2182 - 2195
11
[ 150058-27-8 ]
[ 139481-69-9 ]
Reference：
[1] Patent: CN107056757, 2017, A,
12
[ 124750-51-2 ]
[ 139481-69-9 ]
Reference：
[1] Patent: CN107056757, 2017, A,
13
[ 139481-69-9 ]
[ 139481-59-7 ]
Yield
Reaction Conditions
Operation in experiment
95%
Stage #1: With sodium hydroxide; water In methanol at 78 - 80℃; for 1 h; Stage #2: With acetic acid In ethyl acetate at 10 - 15℃;
To the product obtained in Step A) (350 g) dissolved in methanol (1.17 L) was added sodium hydroxide solution (93 g in 1.17 L water). The reaction mass was heated to reflux at 78-80°C and maintained for 1 hour. After completion of reaction, methanol was completely removed under vacuum at 40-45°C and to the residue was added ethyl acetate (2. 8 L) and water (3.50 L) at room temperature. Stirred the mixture for about 1 hour at 25- 30°C and allowed to settle for 15 minutes. Separated the layers and pH of the aqueous layer was adjusted to 4-5 with acetic acid (about 450 g) at 10-15°C. The precipitated product was filtered and washed twice with water (2 x 0.7 L) and suck dried. The wet cake was air dried at room temperature for 2 hours and then at 50-55°C to afford the title compound. Yield: 323 g (95percent)
90%
at 10 - 70℃;
To 80.0 grams (0.176 moles) of methyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]-methyl] benzimidazole-7-carboxylate, were added 265 ml ofmethanol, 535 ml of water, and 21.1 grams of sodium hydroxide, below 10°C, andthe mixture was heated to 70°C and maintained until the reaction completed. Themethanol was distilled off completely under reduced pressure, and the residuewas cooled to 10°C. The pH of the residue was adjusted to 2 with aqueoushydrochloric acid solution. The precipitated compound was filtered, washed withwater and dried at 60-70°C to get 70.0 grams (90percent) of 2-ethoxy-1-[[2'-(1 H-tetrazol-5-yl)biphenyl-4-yl]-methyl]benzimidazole-7-carboxylicacid.
82%
at 68 - 72℃; for 1 - 2 h; Industry scale
An aqueous sodium hydroxide solution (73 kg/826L) was added to the wet MET (369.6 kg) obtained in Reference Example 9, and the mixture was stirred at 68 to 72 °C for 1 to 2 hours. The reaction solution was cooled, and washed twice with methylene chloride (486 kg) and once with toluene (366 L). Methanol (1437 L) was added to the aqueous layer, the pH was adjusted to 7.0 +/-0.5 with concentrated hydrochloric acid (about 35 L). Activated charcoal (11kg) was added, followed by stirring for about 30 minutes. The activated charcoal was filtered off, and concentrated hydrochloric acid (about 20L) was added until the solution became cloudy, followed by stirring at 25 +/-5°C for about 1 hour. Water (487 L) was added, and the pH was adjusted to 3.5 +/-0.3 with concentrated hydrochloric (about 85 L). After stirring at 24 to 30°C for about 30 minutes, water (687 L) was added, and the mixture was cooled to 10°C or lower, and stirred for about 1 hour. The crystals were separated, washed with water (412 L) and then acetone (427 L), ground, and dried to give 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]benzimidazole-7-carboxylic acid (200kg, 82.0percent). mp.183-185°C 1NMR (200MHz, DMSO-d6) δ: 1.38(3H,t), 4.58(2H,q), 5.63(2H,s), 6.97(4H.q), 7.17(1H,t), 7.47-7.68(6H,m) IR (KBr) cm-1:1710, 1550, 1480, 1430, 1280, 1240, 1040, 760
Preparation of 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]- lH-benzimidazole-7-carboxylic acid methyl ester To 2-ethoxy-1-[[2'-cyano [l, 1'-biphenyl] -4-yl] methyl]-lH-benzimidazole-7- carboxylic acid methyl ester of Formula IV (310 g) in toluene (2.48 L) added tributyltin chloride (737 g) and sodium azide (146 g) and tetrabutyl ammonium bromide (31 g). The resultant mass was slowly heated to 110°C and maintained for 24 hours at 110-115°C. The reaction was monitored by TLC and after completion of reaction, the reaction mass was cooled to 15°C. Added methanol (3.1 L) and water (2.17 L) to the reaction mass followed by addition of acetic acid (930 g). The resultant mixture was stirred at 15-20°C for 1 hour to allow separation of the product. Charged toluene (1.24 L) at 15-20°C and filtered the reaction mass. Washed the cake thoroughly with water (0.93 L) to completely remove the acidity (until the pH of the washing is between about 5.5 to about 7.0). Washed the cake with toluene (0.62 L) and suck dried. Air dried the product at 50-55°C to afford the title compound. Yield: 290 g (85percent)
Compound I, 1-(2'-cyanobiphenyl-4-yl)methyl)-2-ethoxybenzimidazole-7-carboxylic acid methyl ester (111 g, 270 mmol), is reacted in an aromatic hydrocarbon, preferably toluene, xylolene or mesitylene (typically, 500-1000 mL), with alkali metal azides and another reagent (ammonium halide derivatives, typically, triethylamine hydrochloride or organotin halides, typically, tetramethyltin chloride or tetrabutyltin chloride), while heating, to form compound II, 2-ethoxy-1-((2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl)benzimidazole-7-carboxylic acid methyl ester. After completion of the reaction, the reaction solution is stirred with water or a saline solution (250 mL), whereupon the solids dissolve and a three-phase liquid system forms. If only two phases are present, petroleum spirit 80/110 is added until there are three phases which can be separated well. The lower phase is separated; the two upper phases are washed with water or a saline solution (200 mL).
With tri-n-octyltin azide; In toluene; at 112 - 120℃; for 40h;Heating / reflux; Industry scale;
The methyl 1-[(2'-cyanobiphenyl-4-yl)methyl]2-ethoxybenzimidazole-7-carboxylate [BEC] (228 kg) obtained in Reference Example 7, the concentrate of trioctyltin azide [TOTA] obtained in Reference Example 8 and toluene (1148 L) were heated (115 to 120°C) under reflux for about 40 hours. The reaction solution was cooled, and concentrated under reduced pressure. Ethanol (764 kg) and an aqueous sodium nitrite solution (135 kg/460 L) were added to the residue, and the pH was adjusted to 4.5 to 5.5 with concentrated hydrochloric acid (about 224 kg). Ethyl acetate (735 L) was added thereto, and the pH was adjusted to 0.5 to 1.5 with concentrated hydrochloric acid (about 100 L). Hexane (1005 L) was added, and the pH was adjusted to 3.5 +/- 0.5 with 4percent aqueous sodium hydroxide solution. The solution was cooled to 10°C or lower, and stirred for 1 hour. The crystals were separated, and washed with a mixture of ethyl acetate (106 L) and hexane (310 L), and then with hexane (410 L) to give wet MET (396.6 kg).
With sodium azide; tributyltin chloride; In toluene; for 100h;Reflux;
To sodium azide (48 gm) was added water (500 ml), cooled to O0C, tributyl tin chloride (240 gm) was added, maintained for 2 hours 30 minutes, added toluene (500 ml) and then allowed the temperature to rise to room temperature. Separated the layers, re-extracted using toluene (500 ml) and organic layer washed with 10percent sodium chloride solution (480 ml). Methyl-1-[(2- cyanobiphenyI-4-yl)methyl]-2-ethoxy benzimidazole-7-carboxylate (100 gm) was added to above solution, refluxed for 100 hours, cooled to room temperature and then to 100C. Methanol (400 ml), water (300),and acetic acid (320 ml) were added at O0C. Stirred for 8 hours at room temperature, then cooled to O0C, stirred for 3 hours, filtered, washed with toluene (400 ml) and dried the solid at 600C to get Methyl-2-ethoxy-1-[[2'-(1 H-tetrazole-5-yl)biphenyl-4-yl]methyl] benzimidazole- 7-carboxylate (80 gm, HPLC purity: 96percent).
To 75.0 grams of methyl 1-[(2'-cyanobiphenyl-4-yl)methyl]-2-ethoxy-benzimidazole-7-carboxylate were added 375 ml xylene and 2.5 moles of tri-n-butyltin azide, which was prepared with sodium azide and tri-n-butyltin chloride inthe presence of water and extracted with methylene chloride. The mixture wasslowly heated to reflux and maintained for 24 hours, and then the solvent wasevaporated under reduced pressure. The residue was dissolved in 225 ml ofmethanol and 225 ml of water followed by the addition of 91.3 grams of sodiumnitrite and 75 ml of ethyl acetate. The pH of the resulting solution was adjusted to3 with aqueous hydrochloric acid. The upper liquid layer was decanted and 225ml of ethyl acetate was added. The solid was filtered, washed with ethyl acetate,and dried at 50-60°C to get 82.0 grams (98percent) of methyl 2-ethoxy-1-[[2'-(1 H-tetrazol-5-yl)biphenyl-4-yl]-methyl]benzimidazole-7-carboxylate.
With azido tributyltin (IV); In N,N-dimethyl-formamide; at 140 - 150℃; for 20h;
Trityl candesartan was prepared from candesartan cyclic compound in the similar manner as Example 1. The results are shown in the following table.
To the product obtained in Step A) (350 g) dissolved in methanol (1.17 L) was added sodium hydroxide solution (93 g in 1.17 L water). The reaction mass was heated to reflux at 78-80C and maintained for 1 hour. After completion of reaction, methanol was completely removed under vacuum at 40-45C and to the residue was added ethyl acetate (2. 8 L) and water (3.50 L) at room temperature. Stirred the mixture for about 1 hour at 25- 30C and allowed to settle for 15 minutes. Separated the layers and pH of the aqueous layer was adjusted to 4-5 with acetic acid (about 450 g) at 10-15C. The precipitated product was filtered and washed twice with water (2 x 0.7 L) and suck dried. The wet cake was air dried at room temperature for 2 hours and then at 50-55C to afford the title compound. Yield: 323 g (95%)
90%
With methanol; sodium hydroxide; water; at 10 - 70℃;
To 80.0 grams (0.176 moles) of methyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]-methyl] benzimidazole-7-carboxylate, were added 265 ml ofmethanol, 535 ml of water, and 21.1 grams of sodium hydroxide, below 10C, andthe mixture was heated to 70C and maintained until the reaction completed. Themethanol was distilled off completely under reduced pressure, and the residuewas cooled to 10C. The pH of the residue was adjusted to 2 with aqueoushydrochloric acid solution. The precipitated compound was filtered, washed withwater and dried at 60-70C to get 70.0 grams (90%) of 2-ethoxy-1-[[2'-(1 H-tetrazol-5-yl)biphenyl-4-yl]-methyl]benzimidazole-7-carboxylicacid.
82%
With sodium hydroxide; water; at 68 - 72℃; for 1 - 2h;Industry scale;
An aqueous sodium hydroxide solution (73 kg/826L) was added to the wet MET (369.6 kg) obtained in Reference Example 9, and the mixture was stirred at 68 to 72 C for 1 to 2 hours. The reaction solution was cooled, and washed twice with methylene chloride (486 kg) and once with toluene (366 L). Methanol (1437 L) was added to the aqueous layer, the pH was adjusted to 7.0 +/-0.5 with concentrated hydrochloric acid (about 35 L). Activated charcoal (11kg) was added, followed by stirring for about 30 minutes. The activated charcoal was filtered off, and concentrated hydrochloric acid (about 20L) was added until the solution became cloudy, followed by stirring at 25 +/-5C for about 1 hour. Water (487 L) was added, and the pH was adjusted to 3.5 +/-0.3 with concentrated hydrochloric (about 85 L). After stirring at 24 to 30C for about 30 minutes, water (687 L) was added, and the mixture was cooled to 10C or lower, and stirred for about 1 hour. The crystals were separated, washed with water (412 L) and then acetone (427 L), ground, and dried to give 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]benzimidazole-7-carboxylic acid (200kg, 82.0%). mp.183-185C 1NMR (200MHz, DMSO-d6) delta: 1.38(3H,t), 4.58(2H,q), 5.63(2H,s), 6.97(4H.q), 7.17(1H,t), 7.47-7.68(6H,m) IR (KBr) cm-1:1710, 1550, 1480, 1430, 1280, 1240, 1040, 760
The middle phase is isolated and stirred with potassium hydroxide in ethanol (2.5N, 400 mL) for 2 h at 40 C. Water (400 mL) is added, and 500 mL liquid are distilled off under reduced pressure. With the addition of 5 g actived carbon and 5 g celite, stirring is carried out for 1 h at 40 C., followed by filtration. Ethyl acetate (720 mL) is added to the filtrate and acidification is carried out with hydrochloric acid (5-6N) to pH 2.0, while stirring vigorously and with ice cooling. The organic phase is washed with 300 mL water, and after separation of the washing phase, an aliphatic hydrocarbon or a mixture of aliphatic hydrocarbons (480 mL) is added dropwise, preferably, methylcyclohexane or petroleum spirit 80/110. The residual water present in the system is separated out by means of a water separator. Cooling is done slowly to 5 C., at which point crystallization begins. The solids are filtered off, washed with a mixture of ethyl acetate and hydrocarbon, and dried at 40 C. in a vacuum.
Sodium hydroxide (30 gm) dissolved in water (600 ml) was added to Methyl-2-ethoxy-1-[[2'-(1H-tetrazole-5-yl)biphenyI-4-yl]methyl]benzimidazole-7- <n="5"/>carboxylate (100 gm) in ethanol (600 ml) and refluxed for 3 hours 30 minutes then ethanol was removed by distillation and then water (600 ml) and ethyl acetate (600 ml) were added at room temperature, stirred for 30 minutes. Separated the layers, pH of the aqueous layer was adjusted to 4 by using acetic acid at O0C, stirred for 3 hours, filtered, washed with water (200 ml) and dried to give Candesartan (133 gm, HPLC purity: 97%).
Sodium hydroxide (30 gm) dissolved in water (600 ml) was added to Methyl-2- ethoxy- 1 -[[2'-( 1 H-tetrazole-5-yl)biphenyl-4-yl]methyl]benzimidazole-7-carboxylate(100 gm) in ethanol (600 ml) and refluxed for 3 hours 30 minutes then ethanol was removed by distillation and then water (600 ml) and ethyl acetate (600 ml) were added at room temperature, stirred for 30 minutes. Separated the layers, pH of the aqueous layer was adjusted to 4 by using acetic acid at 0C, stirred for 3 hours, filtered, washed with water (200 ml) and dried to give 133 gm of Candesartan.
With water; sodium hydroxide; at 70 - 80℃; for 20h;
Trityl candesartan was prepared from candesartan cyclic compound in the similar manner as Example 1. The results are shown in the following table.
With potassium carbonate; In N,N-dimethyl-formamide; at 60 - 65℃; for 1 - 3h;
50 grams of methyl 2-ethoxy-1-[[2'- (1 H-tetrazol-5-yl) biphenyl-4-yl]-methyl]benzimidazole-7-carboxylate, 100 ml of N, N-dimethylformamide, 22.6 grams ofbenzylbromide and 45.7 grams of potassium carbonate were charged in a roundbottom flask. The reaction mass was heated to about 60-65C and stirred forabout 1-3 hours followed by cooling to about 25-30C. Reaction mass wasquenched with a mixture of sodium chloride (100 grams) and water (1 litre) understirring. Reaction mass was extracted with 2x250 ml and was washed with 2x250ml water. Organic and aqueous layers were separated and evaporated the solventcompletely by distillation at about 35-40C
The compounds produced in accordance with the process of the invention are specifically disclosed as follows: (+-)-1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylate, 2-ethoxy-1-[[2'(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylic acid, Ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]benzimidazole-7-carboxylate, Methyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]benzimidazole-7-carboxylate, Methyl 2-methoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]benzimidazole-7-carboxylate, 2-Methoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]benzimidazole-7-carboxylic acid, Pivaloyloxymethyl 2-butyl-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylate, Pivaloyloxymethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]benzimidazole-7-carboxylate, Ethyl 2-Propoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]benzimidazole-7-carboxylate, ...
13
trioctyltin azide (tri-n-octyltin azide)[ No CAS ]
[ 139481-44-0 ]
[ 139481-69-9 ]
Yield
Reaction Conditions
Operation in experiment
100%
With sodium nitrite; In ethanol; hexane; ethyl acetate; toluene;
EXAMPLE 5 Methyl 2-ethoxy-1-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methylbenzimidazole-7-carboxylate A mixture of 13.0 g of methyl 1-(2'-cyanobiphenyl-4-yl)methyl-2-ethoxybenzimidazole-7-carboxylate, 47.1 g of trioctyltin azide (tri-n-octyltin azide) and 60 ml of toluene was refluxed at 125° C. for 31 hours. After cooling, the reaction mixture was concentrated. To the concentrate was added 56 ml of ethanol as well as an aqueous solution of sodium nitrite (7.7 g/28 ml) and the mixture was adjusted to pH 5 with concentrated hydrochloric acid. Then, 31 ml of ethyl acetate was added. The mixture was further adjusted to pH 1.1 with concentrated hydrochloric acid, diluted with 20 ml of n-hexane and adjusted to pH 3.3 with 1N aqueous sodium hydroxide solution. The crystals were separated, washed with ethyl acetate/n-hexane mixture (1:3) and dried to provide 14.56 g of methyl 2-ethoxy-1-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methylbenzimidazole-7carboxylate. Yield 100percent. 1 H NMR (CDCl3) delta: 1.42 (3H, t), 3.56 (3H, s), 4.27 (2H, q), 5.54 (2H, s), 6.70 (2H, d), 6.78-6.95 (4H, m), 7.28-7.33 (1H, m), 7.40 (1H, dd), 7.56-7.66 (2H, m), 8.02-8.06 (1H, m) IR(KBr): 1720, 1618, 1548, 1476, 1432, 1390, 1354, 1324, 1284, 1222, 1134, 1042, 872, 840, 820, 780, 756 cm-1.
methyl 2-ethoxy-1-<<2'-<N-(triphenylmethyl)tetrazol-5-yl>biphenyl-4-yl>methyl>-1H-benzimidazole-7-carboxylate[ No CAS ]
[ 139481-69-9 ]
Yield
Reaction Conditions
Operation in experiment
56 g
With hydrogenchloride; In methanol; water; for 3h;Reflux;
In the reaction container plus 1000 ml methanol, vote under stirring 100 g compound 3, to the reaction solution is slowly dropped into the building material in 45 ml, the completion of the dropping, the reaction solution is heated to reflux, thermal insulation reaction 2 - 3 hours, the raw materials after the reaction, the reaction liquid cooling to 5 - 10 C, thermal insulation 1 hour after-filtration, the filter cake is washed with water to neutral. Drying, a yellow solid 56 g, HPLC detection, purity 96.72%.
methyl 1-[(2-cyanobiphenyl-4-yl)methyl]-2-ethoxybenzimidazole-7-carboxylate[ No CAS ]
[ 139481-69-9 ]
Yield
Reaction Conditions
Operation in experiment
To sodium azide (48 gm) was added water (500 ml), cooled to 0C, tributyl tin chloride (240 gm) was added, maintained for 2 hours 30 minutes, added toluene (500 ml) and then allowed the temperature to rise to room temperature. Separated the layers, re-extracted using toluene (500 ml) and organic layer washed with 10% sodium chloride solution (480 ml). Methyl- l-[(2-cyanobiphenyl-4-yl)methyl]-2-ethoxy benzimidazole-7- carboxylate (100 gm) was added to above solution, refluxed for 100 hours, cooled to room temperature and then to 10C. Methanol (400 ml), water (300),and acetic acid (320 ml) were added at 0C. Stirred for 8 hours at room temperature, then cooled to 0C, stirred for 3 hours, filtered, washed with toluene (400 ml) and dried the solid at 60C to get 80 gm of methyl-2-ethoxy-l-[[2'-(lH-tetrazole-5-yl)biphenyl-4-yl]methyl] benzimidazole-7-carboxylate.
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