124750-51-2

Basic information

• Product Name: 5-(4'-Bromomethyl-1,1'-biphenyl-2-yl)-1-triphenylmethyl-1H-tetrazole
• Synonyms: N-(Triphenylmethyl)-5-(4'-bromomethylbiphenyl-2-yl-)terazole;N-(TRIPHENYLMETHYL)-5-(4'-BROMOMETHYLBIPHENYL-2-YL) TETRAZOLE;5-(4'-BROMOMETHYL-1,1'-BIPHENYL-2-YL)-1-TRIPHENYLMETHYL-1H-TETRAZOLE;5-(4'-BROMOMETHYL-BIPHENYL-2-YL)-1-TRITYL-1H-TETRAZOLE;1H-Tetrazole, 5-[4'-(bromomethyl)[1,1'-biphenyl]-2-yl]-1-(triphenylmethyl)-;Trityl tetrazole bromomethyl biphenyl;5-(4'-(BROMOMETHYL)(1,1'-BIPHENYL)-2-YL)-1-TRITYL-;5-[4'-(Bromomethyl)[1,1'-Biphenyl]-1-(Triphenylmethyl)Tetrazole]
• CAS NO: 124750-51-2
• Molecular Formula: C₃₃H₂₅BrN₄
• Molecular Weight: 557.48
• EINECS: 1592732-453-0
• Product Categories: INTERMEDIATESOF;Biphenyl & Diphenyl ether;Tetrazoles;API intermediates;(intermediates of candesartan cilexetil);Hypertension;Amines;Aromatics;Heterocycles;Intermediates
• Mol File: 124750-51-2.mol
• Article Data: 29

Chemical Properties

• Melting Point: 152-155°C
• Boiling Point: 61°C/12mmHg(lit.)
• Flash Point: 388.299 °C
• Appearance: off-white solid
• Density: 1.282 g/cm³
• Storage Temp.: -20?C Freezer
• PKA: 0.29±0.10(Predicted)
• Stability: Moisture Sensitive
• CAS DataBase Reference: 5-(4'-Bromomethyl-1,1'-biphenyl-2-yl)-1-triphenylmethyl-1H-tetrazole(CAS DataBase Reference)
• NIST Chemistry Reference: 5-(4'-Bromomethyl-1,1'-biphenyl-2-yl)-1-triphenylmethyl-1H-tetrazole(124750-51-2)
• EPA Substance Registry System: 5-(4'-Bromomethyl-1,1'-biphenyl-2-yl)-1-triphenylmethyl-1H-tetrazole(124750-51-2)

Safety Data

• RIDADR: UN 2811 6.1/PG III
• HazardClass: 6.1
• PackingGroup: III
• Hazardous Substances Data: 124750-51-2(Hazardous Substances Data)

Usage

Chemical Properties

Off-White Solid

Uses

An intermediate in the synthesis of Losartan and Valsartan

Synthetic route

N-triphenylmethyl-5-(4'-methylbiphenyl-2-yl)tetrazole (124750-53-4) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
With bromine In hexane; water at 69℃; for 0.433333h; Temperature; Solvent; Irradiation; Flow reactor;	95.2%
With sodium bromate; sodium hydrogensulfite In water; 1,2-dichloro-ethane at 20℃; Product distribution / selectivity;	90%
With N-Bromosuccinimide; dihydrogen peroxide In dichloromethane Reflux;	88%

4'-hydroxymethyl-2-(N-trityl-1H-tetrazol-5-yl)biphenyl (154709-18-9) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
With phosphorus tribromide In dichloromethane at 10 - 20℃; for 1h;	95.07%
With sulfuric acid; potassium bromide In N,N-dimethyl acetamide at 10 - 25℃; for 7h; Reagent/catalyst; Solvent;	81.4%

N-triphenylmethyl-5-(4'-methylbiphenyl-2-yl)tetrazole (124750-53-4) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) + 5-(4'-Dibromomethyl-biphenyl-2-yl)-1-trityl-1H-tetrazole

Conditions	Yield
With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); sodium acetate; acetic acid In dichloromethane for 16h; Heating;	A 76% B 7%
With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; 2,2'-azobis(isobutyronitrile) In chlorobenzene at 80℃; Overall yield = 78.6 %;

salicylonitrile (611-20-1) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: 98 percent / pyridine / 1.) 0 deg C, 5 min, 2.) r.t., 25 h 2: 1.) Mg, I2; n-Bu3SnCl, 2.) Pd(PPh3)2Cl2, LiCl / 1.) THF, reflux, 30 min; THF, reflux, 20 h, 2.) DMF, 98 deg C, 24 h 3: 1.) NaN3, n-Bu3SnCl, 2.) NaOH / 1.) toluene, 115 deg C, 70 h, 2.) toluene, r.t., 3 h 4: NBS, AIBN / CCl4 / 3 h / Heating View Scheme

4-tolyl iodide (624-31-7) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) Mg, I2; n-Bu3SnCl, 2.) Pd(PPh3)2Cl2, LiCl / 1.) THF, reflux, 30 min; THF, reflux, 20 h, 2.) DMF, 98 deg C, 24 h 2: 1.) NaN3, n-Bu3SnCl, 2.) NaOH / 1.) toluene, 115 deg C, 70 h, 2.) toluene, r.t., 3 h 3: NBS, AIBN / CCl4 / 3 h / Heating View Scheme

o-cyanobromobenzene (2042-37-7) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) Mg, I2; n-Bu3SnCl, 2.) Pd(PPh3)2Cl2, LiCl / 1.) THF, reflux, 30 min; THF, reflux, 20 h, 2.) DMF, 98 deg C, 24 h 2: 1.) NaN3, n-Bu3SnCl, 2.) NaOH / 1.) toluene, 115 deg C, 70 h, 2.) toluene, r.t., 3 h 3: NBS, AIBN / CCl4 / 3 h / Heating View Scheme
Multi-step reaction with 3 steps 1: bis-triphenylphosphine-palladium(II) chloride; lithium chloride / N,N-dimethyl-formamide / Inert atmosphere 2: sodium azide; tributyltin chloride / toluene / Reflux 3: N-Bromosuccinimide; dibenzoyl peroxide / tetrachloromethane View Scheme
Multi-step reaction with 4 steps 1.1: palladium dichloride / methanol; toluene / 0.17 h / 20 °C / Inert atmosphere 1.2: 12 h / 110 °C / Inert atmosphere 2.1: zinc(II) chloride; sodium azide / N,N-dimethyl-formamide / 48 h / 120 °C 3.1: triethylamine / dichloromethane / 2 h / 0 °C / Reflux 4.1: dibenzoyl peroxide; N-Bromosuccinimide / tetrachloromethane / 3 h / Reflux View Scheme

2-Cyano-4'-methylbiphenyl (114772-53-1) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) NaN3, n-Bu3SnCl, 2.) NaOH / 1.) toluene, 115 deg C, 70 h, 2.) toluene, r.t., 3 h 2: NBS, AIBN / CCl4 / 3 h / Heating View Scheme
Multi-step reaction with 3 steps 1: sodium azide; triethylamine hydrochloride / toluene / 18 h / 105 - 110 °C 2: toluene / 3 h / 20 °C 3: N-Bromosuccinimide; dihydrogen peroxide / dichloromethane / Reflux View Scheme
Multi-step reaction with 2 steps 1: sodium azide; tributyltin chloride / toluene / Reflux 2: N-Bromosuccinimide; dibenzoyl peroxide / tetrachloromethane View Scheme

trityl chloride (76-83-5) + DL-lysine methyl ester dihydrochloride → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) NaN3, n-Bu3SnCl, 2.) NaOH / 1.) toluene, 115 deg C, 70 h, 2.) toluene, r.t., 3 h 2: NBS, AIBN / CCl4 / 3 h / Heating View Scheme

2-<(trifluoromethanesulfonyl)oxy>benzonitrile (138313-23-2) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) Mg, I2; n-Bu3SnCl, 2.) Pd(PPh3)2Cl2, LiCl / 1.) THF, reflux, 30 min; THF, reflux, 20 h, 2.) DMF, 98 deg C, 24 h 2: 1.) NaN3, n-Bu3SnCl, 2.) NaOH / 1.) toluene, 115 deg C, 70 h, 2.) toluene, r.t., 3 h 3: NBS, AIBN / CCl4 / 3 h / Heating View Scheme

2-(tetrazol-5-yl)-4'-methyl-1,1'-biphenyl (120568-11-8) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: toluene / 3 h / 20 °C 2: N-Bromosuccinimide; dihydrogen peroxide / dichloromethane / Reflux View Scheme
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / 0 °C / Reflux 2: dibenzoyl peroxide; N-Bromosuccinimide / tetrachloromethane / 3 h / Reflux View Scheme
Multi-step reaction with 2 steps 1: potassium hydroxide / methanol 2: bromine; acetic acid View Scheme

tributyl(p-tolyl)stannane (31614-66-1) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: bis-triphenylphosphine-palladium(II) chloride; lithium chloride / N,N-dimethyl-formamide / Inert atmosphere 2: sodium azide; tributyltin chloride / toluene / Reflux 3: N-Bromosuccinimide; dibenzoyl peroxide / tetrachloromethane View Scheme

4-methylphenylboronic acid (5720-05-8) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: palladium dichloride / methanol; toluene / 0.17 h / 20 °C / Inert atmosphere 1.2: 12 h / 110 °C / Inert atmosphere 2.1: zinc(II) chloride; sodium azide / N,N-dimethyl-formamide / 48 h / 120 °C 3.1: triethylamine / dichloromethane / 2 h / 0 °C / Reflux 4.1: dibenzoyl peroxide; N-Bromosuccinimide / tetrachloromethane / 3 h / Reflux View Scheme
Multi-step reaction with 4 steps 1: palladium diacetate; triethylamine; triphenylphosphine / acetonitrile 2: sodium azide / N,N-dimethyl-formamide 3: potassium hydroxide / methanol 4: bromine; acetic acid View Scheme
Multi-step reaction with 4 steps 1: palladium diacetate; triphenylphosphine / acetonitrile 2: sodium azide / N,N-dimethyl-formamide 3: potassium hydroxide / methanol 4: bromine; acetic acid View Scheme

o-tolylbenzoic acid (7148-03-0) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 6 steps 1: thionyl chloride 2: sodium hydroxide 3: trimethylsilylazide; diethylazodicarboxylate; triphenylphosphine 4: sodium hydroxide / tetrahydrofuran; methanol 5: N-ethyl-N,N-diisopropylamine 6: N-Bromosuccinimide / tetrachloromethane View Scheme

4'-methylbiphenyl-2-carboxylic acid chloride (114772-35-9) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 5 steps 1: sodium hydroxide 2: trimethylsilylazide; diethylazodicarboxylate; triphenylphosphine 3: sodium hydroxide / tetrahydrofuran; methanol 4: N-ethyl-N,N-diisopropylamine 5: N-Bromosuccinimide / tetrachloromethane View Scheme

N-(2-cyanoethyl)-4'-methyl[1,1']biphenyl-2-carboxamide (120568-15-2) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: trimethylsilylazide; diethylazodicarboxylate; triphenylphosphine 2: sodium hydroxide / tetrahydrofuran; methanol 3: N-ethyl-N,N-diisopropylamine 4: N-Bromosuccinimide / tetrachloromethane View Scheme

5-<4'-Methyl-1,1'-biphenyl-2-yl>-1H-tetrazole-1-propanenitrile (120568-17-4) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium hydroxide / tetrahydrofuran; methanol 2: N-ethyl-N,N-diisopropylamine 3: N-Bromosuccinimide / tetrachloromethane View Scheme

C17H20N4Si → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 2 steps 2: N-Bromosuccinimide / tetrachloromethane View Scheme

C26H22Zn → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: nickel 2: toluene 4: N-Bromosuccinimide / tetrachloromethane View Scheme

para-bromotoluene (106-38-7) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 6 steps 1: magnesium / tetrahydrofuran / 2 h / 20 °C 2: tetrahydrofuran / 3 h / 20 °C 3: pyridine; trichlorophosphate / 3 h / 10 - 100 °C 4: toluene 6: N-Bromosuccinimide / tetrachloromethane View Scheme
Multi-step reaction with 9 steps 1: magnesium / tetrahydrofuran / 2 h / 20 °C 2: tetrahydrofuran / 3 h / 20 °C 3: hydrogenchloride / water 4: thionyl chloride 5: sodium hydroxide 6: trimethylsilylazide; diethylazodicarboxylate; triphenylphosphine 7: sodium hydroxide / tetrahydrofuran; methanol 8: N-ethyl-N,N-diisopropylamine 9: N-Bromosuccinimide / tetrachloromethane View Scheme

para-methylphenylmagnesium bromide (4294-57-9) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 5 steps 1: tetrahydrofuran / 3 h / 20 °C 2: pyridine; trichlorophosphate / 3 h / 10 - 100 °C 3: toluene 5: N-Bromosuccinimide / tetrachloromethane View Scheme
Multi-step reaction with 8 steps 1: tetrahydrofuran / 3 h / 20 °C 2: hydrogenchloride / water 3: thionyl chloride 4: sodium hydroxide 5: trimethylsilylazide; diethylazodicarboxylate; triphenylphosphine 6: sodium hydroxide / tetrahydrofuran; methanol 7: N-ethyl-N,N-diisopropylamine 8: N-Bromosuccinimide / tetrachloromethane View Scheme

4,4-dimethyl-2-(4'-methyl-biphenyl-2-yl)-4,5-dihydrooxazole (84392-32-5) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: pyridine; trichlorophosphate / 3 h / 10 - 100 °C 2: toluene 4: N-Bromosuccinimide / tetrachloromethane View Scheme
Multi-step reaction with 7 steps 1: hydrogenchloride / water 2: thionyl chloride 3: sodium hydroxide 4: trimethylsilylazide; diethylazodicarboxylate; triphenylphosphine 5: sodium hydroxide / tetrahydrofuran; methanol 6: N-ethyl-N,N-diisopropylamine 7: N-Bromosuccinimide / tetrachloromethane View Scheme

4'-(hydroxymethyl)-[1,1'-biphenyl]-2-carbonitrile (154709-19-0) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: zinc(II) chloride; sodium azide / butan-1-ol / 20 h / 100 - 105 °C 2.1: triethylamine / dichloromethane / 10 - 15 °C 2.2: 10 °C / Reflux 3.1: potassium bromide; sulfuric acid / N,N-dimethyl acetamide / 7 h / 10 - 25 °C View Scheme

biphenyl-2-carbonitrile (24973-49-7) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: zinc(II) chloride; hydrogenchloride / 1,2-dimethoxyethane; water / 0 - 5 °C 2.1: zinc(II) chloride; sodium azide / butan-1-ol / 20 h / 100 - 105 °C 3.1: triethylamine / dichloromethane / 10 - 15 °C 3.2: 10 °C / Reflux 4.1: potassium bromide; sulfuric acid / N,N-dimethyl acetamide / 7 h / 10 - 25 °C View Scheme

C35H28N4O2 → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: hydrogenchloride / tetrahydrofuran; water / 3 h / 20 °C 2.1: sodium tetrahydroborate / methanol / 1 h / 5 - 20 °C 2.2: 0.25 h / 0 °C 3.1: phosphorus tribromide / dichloromethane / 1 h / 10 - 20 °C View Scheme

5-<2-(4'-formylbiphenylyl)>-2-(triphenylmethyl)-2H-tetrazole (155983-56-5) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium tetrahydroborate / methanol / 1 h / 5 - 20 °C 1.2: 0.25 h / 0 °C 2.1: phosphorus tribromide / dichloromethane / 1 h / 10 - 20 °C View Scheme

2-(4-chlorophenyl)-1,3-dioxolane (2403-54-5) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: magnesium; iodine / tetrahydrofuran; toluene / 5 h / Inert atmosphere; Reflux 2.1: tributyltin chloride; sodium azide / toluene; N,N-dimethyl-formamide / 48 h / Reflux 3.1: hydrogenchloride / tetrahydrofuran; water / 3 h / 20 °C 4.1: sodium tetrahydroborate / methanol / 1 h / 5 - 20 °C 4.2: 0.25 h / 0 °C 5.1: phosphorus tribromide / dichloromethane / 1 h / 10 - 20 °C View Scheme

2-Chlorobenzonitrile (873-32-5) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: magnesium; iodine / tetrahydrofuran; toluene / 5 h / Inert atmosphere; Reflux 2.1: tributyltin chloride; sodium azide / toluene; N,N-dimethyl-formamide / 48 h / Reflux 3.1: hydrogenchloride / tetrahydrofuran; water / 3 h / 20 °C 4.1: sodium tetrahydroborate / methanol / 1 h / 5 - 20 °C 4.2: 0.25 h / 0 °C 5.1: phosphorus tribromide / dichloromethane / 1 h / 10 - 20 °C View Scheme

2-propyl-4,5-bis(methoxycarbonyl)-imidazole (124750-59-0) + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → 2-propyl-1-[2'-(1-triphenylmethyl-1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-1H-imidazole-4,5-dicarboxylic acid dimethyl ester (124750-61-4)

Conditions	Yield
With potassium carbonate In N,N-dimethyl acetamide; acetone Reflux; Large scale reaction;	99%

N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → [2'-(N-Triphenylmethyl-tetrazol-5-yl)-biphenyl-4-yl]methyl azide (124806-66-2)

Conditions	Yield
In N-methyl-acetamide	96%
With sodium azide In N,N-dimethyl-formamide at 70℃; for 0.333333h;	96%
In dimethyl sulfoxide
With sodium azide In water; N,N-dimethyl-formamide at 20℃; for 22h;

[2'-(N-Triphenylmethyl-tetrazol-5-yl)-biphenyl-4-yl]methyl azide (124806-66-2) + 5-butyl-2,4-dihydro-4-[[2-(1-triphenylmethyl-1H-tetrazol-5-yl)-[1,1'-biphenyl]-4'-yl]methyl]-3H-1,2,4-triazol-3-one (169598-69-0) + dichloromethane (75-09-2) + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → 2,4-Bis[[2'-(N-trityltetrazol-5-yl)biphenyl-4-yl]methyl]-5-n-butyl-2,4-dihydro-3H-1,2,4-triazol-3-one

Conditions	Yield
In methanol	96%

L-valine benzyl ester hydrochloride (2462-34-2) + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → N-[(2'-(1-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl)methyl]-(L)-valine benzyl ester phosphite

Conditions	Yield
Stage #1: L-valine benzyl ester hydrochloride With sodium hydroxide In water; ethyl acetate for 0.333333h; pH=10 - 12; Stage #2: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole In ethyl acetate at 55 - 60℃; Stage #3: With phosphonic Acid In ethyl acetate for 1h;	95%

L-valine benzyl ester hydrochloride (2462-34-2) + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → N-[(2'-(1-triphenylmethyltetrazol-5-yl)biphenyl-4-yl)methyl]-(L)-valine benzyl ester phosphorous acid salt

Conditions	Yield
Stage #1: L-valine benzyl ester hydrochloride With sodium hydroxide In water pH=10 - 12; Stage #2: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole In ethyl acetate at 55 - 60℃; Stage #3: With phosphorous acid In ethyl acetate for 1h;	95%

2-(2-n-butyl-4-hydroxy-6-methylpyrimidin-5-yl)-N,N-dimethylthioacetamide + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → 2-n-butyl-5-(N,N-dimethylaminothioformylmethyl)-6-methyl-3-[[2'-(N-triphenylmethyl-5-tetrazolyl)biphenyl]-4-methyl]pyrimidin-4-one (1361024-52-3)

Conditions	Yield
Stage #1: 2-(2-n-butyl-4-hydroxy-6-methylpyrimidin-5-yl)-N,N-dimethylthioacetamide With lithium hydride In hexane; N,N-dimethyl-formamide at 0℃; for 1h; Inert atmosphere; Stage #2: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole In hexane; N,N-dimethyl-formamide at 70℃; for 24h; Inert atmosphere;	95%

N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) + 2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one hydrochloride → 2-n-butyl-4-spirocyclopentane-1-[(2'-(tetrazol-5-yl)biphenyl-4-yl)methyl]-2-imidazolin-5-one hydrochloride sesquihydrate

Conditions	Yield
Stage #1: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole; 2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one hydrochloride With potassium hydroxide; tetrabutylammomium bromide In water; toluene at 85℃; for 2h; Stage #2: With hydrogenchloride; water In toluene at 55℃; for 0.75h; Product distribution / selectivity;	94%
Stage #1: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole; 2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one hydrochloride With potassium hydroxide; tetrabutylammomium bromide In xylene at 85℃; for 2h; Stage #2: With hydrogenchloride; water In xylene at 55℃; for 0.75h; Product distribution / selectivity;	94%
Stage #1: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole; 2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one hydrochloride With sodium hydroxide; 18-crown-6 ether In xylene at 85℃; for 2 - 4h; Stage #2: With hydrogenchloride; water In xylene at 55℃; for 0.75h; Product distribution / selectivity;	94%

N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) + ethyl 4-(2-hydroxypropan-2-yl)-2-propyl-1H-imidazole-5-carboxylate (144689-93-0) → ethyl 4-(2-hydroxypropan-2-yl)-2-propyl-1-({2'-[1-(triphenylmethyl)-1H-1,2,3,4-tetrazol-5-yl]-[1,1'-biphenyl]-4-yl}methyl)-1H-imidazole-5-carboxylate (144690-33-5)

Conditions	Yield
Stage #1: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole; ethyl 4-(2-hydroxypropan-2-yl)-2-propyl-1H-imidazole-5-carboxylate With potassium carbonate In butanone at 60℃; for 2h; Stage #2: With N,N-dimethyl acetamide In butanone at 45℃; for 4h;	93.8%
With tetrabutylammomium bromide; potassium carbonate In acetone at 50 - 60℃; for 20h; Green chemistry;	90.7%
With potassium carbonate In acetonitrile for 7h; Heating / reflux;	89%

N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) + 2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one hydrochloride → 2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one (138402-11-6)

Conditions	Yield
Stage #1: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole; 2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one hydrochloride With sodium hydroxide; tetrabutylammomium bromide In water; toluene at 85℃; for 2h; Stage #2: With hydrogenchloride; water In acetone at 20℃; Stage #3: With potassium hydroxide In water; acetone Product distribution / selectivity;	92%
With potassium hydroxide; tetra(n-butyl)ammonium hydrogensulfate In water; toluene at 90℃; for 1.5h; Heating / reflux;	84.3%
Stage #1: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole; 2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one hydrochloride With potassium hydroxide; tetra(n-butyl)ammonium hydrogensulfate In water; toluene at 90℃; for 1.5h; Stage #2: With hydrogenchloride; water In acetone at 20℃; Stage #3: With potassium hydroxide In water; acetone Product distribution / selectivity;	84%
Stage #1: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole; 2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one hydrochloride With tetrabutylammomium bromide; potassium carbonate In ethyl acetate at 25 - 80℃; for 10h; Stage #2: With hydrogenchloride In methanol at 0 - 30℃; for 3.5h; Stage #3: With sodium hydroxide In water; toluene at 0 - 30℃; for 0.5h; pH=12;

N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) + 2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one hydrochloride → 2-n-butyl-4-spirocyclopentane-1-[(2'-(tetrazol-5-yl)biphenyl-4-yl)methyl]-2-imidazolin-5-one hydrochloride hemihydrate

Conditions	Yield
Stage #1: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole; 2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one hydrochloride With sodium hydroxide; tetrabutylammomium bromide In water; toluene at 85℃; for 2h; Stage #2: With hydrogenchloride; water In toluene at 55℃; for 0.75h; Product distribution / selectivity;	92%
Stage #1: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole; 2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one hydrochloride With potassium hydroxide In toluene at 85℃; for 2h; Stage #2: With hydrogenchloride; water In toluene at 55℃; for 0.75h; Product distribution / selectivity;	69%
Stage #1: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole; 2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one hydrochloride With potassium carbonate In MIBK (methyl isobutyl ketone); water at 85℃; for 2h; Stage #2: With hydrogenchloride; water In MIBK (methyl isobutyl ketone) at 55℃; for 0.75h; Product distribution / selectivity;	69%

ethyl 2-[(N-tert-butoxycarbonyl)amino]-3-nitrobenzoate (136285-65-9) + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → ethyl 2-[(N-tert-butoxycarbonyl)-[[2'-[1-(triphenylmethyl)-1H-tetrazol-5-yl]biphenyl-4-yl]methyl]amino]-3-nitrobenzoate (906474-56-4)

Conditions	Yield
With potassium carbonate In acetonitrile for 5h; Reflux;	92%
With potassium carbonate In acetonitrile at 80℃; for 7h;

4-methoxy-aniline (104-94-9) + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → 4-methoxy-N-((2'-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl)methyl)aniline

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide Reflux;	92%

2-(2-thienyl)-1,3-diazaspiro[4.4]non-1-en-4-one (1199814-93-1) + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → 2-(2-thienyl)-3-[2'-(1-trityl-1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-1,3-diazaspiro[4.4]non-1-en-4-one (1199814-94-2)

Conditions	Yield
Stage #1: 2-(2-thienyl)-1,3-diazaspiro[4.4]non-1-en-4-one With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.25h; Stage #2: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole In N,N-dimethyl-formamide at 20℃;	91%

N-(3-methoxy)benzyl-4-methyl-2-n-propyl-1H-benzimidazole-6-carboxamide (1239196-62-3) + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → N-(3-methoxy)benzyl-1-([2'-(1-triphenylmethyltetrazol-5-yl)-(1,1'-biphenyl)-4-yl]methyl)-4-methyl-2-n-propyl-1H-benzimidazole-6-carboxamide (1390645-40-5)

Conditions	Yield
Stage #1: N-(3-methoxy)benzyl-4-methyl-2-n-propyl-1H-benzimidazole-6-carboxamide With potassium tert-butylate In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole In N,N-dimethyl-formamide at 0 - 25℃; for 12h;	90.2%

2,2,2-trifluoroacetamide (354-38-1) + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → C35H26F3N5O (868742-05-6)

Conditions	Yield
With 18-crown-6 ether; potassium tert-butylate In tetrahydrofuran; diethyl ether at 20℃; for 96h;	90%

N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) + 2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one hydrochloride → trityl irbesartan (138402-10-5)

Conditions	Yield
In N,N-dimethyl-formamide for 0.0194444h; microwave irradiation;	90%

trityl chloride (76-83-5) + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) + (S)-4-isopropyl-2-(thiophen-2-yl)-4,5-dihydrooxazole (149065-76-9) → (1S)-N-(1-hydroxymethyl-2-methyl-propyl)-N'-[2'-(1-trityl-1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-thiophene-2-carboxamide (1033772-55-2)

Conditions	Yield
With potassium carbonate; potassium iodide In butanone for 24h; Product distribution / selectivity; Heating / reflux;	90%

N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) + 2-amino-phenol (95-55-6) → 2-hydroxy-N-((2'-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl)methyl)aniline

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide Reflux;	90%

N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) + 3-fluoro-4-(morpholinyl)aniline (93246-53-8) → 3-fluoro-4-morpholino-N-((2'-(1-trityl-1H-tetrazol-5-yl)-biphenyl-4-yl)methyl)aniline

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide Reflux;	90%

N-benzyl-4-methyl-2-n-propyl-1H-benzimidazole-6-carboxamide (1239196-56-5) + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → N-benzyl-1-([2'-(1-triphenylmethyltetrazol-5-yl)-(1,1'-biphenyl)-4-yl]methyl)-4-methyl-2-n-propyl-1H-benzimidazole-6-carboxamide (1390645-39-2)

Conditions	Yield
Stage #1: N-benzyl-4-methyl-2-n-propyl-1H-benzimidazole-6-carboxamide With potassium tert-butylate In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole In N,N-dimethyl-formamide at 0 - 25℃; for 12h;	89.7%

N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) + ethyl 4-(2-hydroxypropan-2-yl)-2-propyl-1H-imidazole-5-carboxylate (144689-93-0) → ethyl 4-(2-hydroxypropan-2-yl)-2-propyl-1-({2'-[1-(triphenylmethyl)-1H-1,2,3,4-tetrazol-5-yl]-[1,1'-biphenyl]-4-yl}methyl)-1H-imidazole-5-carboxylate (144690-33-5) + 4-(1-hydroxy-1-methylethyl)-2-propyl-1-(4-(2-(1-(triphenylmethyl)tetrazol-5-yl)phenyl)phenyl)methylimidazole-5-carboxylic acid (761404-85-7) + C45H42N6O2

Conditions	Yield
With potassium phosphate In N,N-dimethyl acetamide at 60 - 65℃; for 6h; Solvent; Reagent/catalyst;	A 89.6% B 0.02% C 0.02%

p-toluidine (106-49-0) + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → 4-methyl-N-((2'-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl)methyl)aniline

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide Reflux;	89%

N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) + (4-acetyl-5-methyl-1-pentanoylamino-1H-pyrrol-2-yl)-acetic acid ethyl ester (230627-21-1) → (4-acetyl-5-methyl-1-{pentanoyl-[2'-(1-trityl-1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-amino}-1H-pyrrol-2-yl)-acetic acid ethyl ester (230627-26-6)

Conditions	Yield
With sodium hydroxide In dichloromethane at 20℃; Alkylation;	88.7%

1H-Naphtho<2,3-d><1,2,3>triazole (269-12-5) + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → 1-[2'-(1-triphenylmethyl-1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-1H-naphtho[2,3-d][1,2,3]triazole (194417-18-0)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 0℃; 1.) 1h, 2.) 0 deg C, 4 h; r.t., overnight;	88%

4-amino-benzoic acid (150-13-0) + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → 4-carboxy-N-((2'-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl)methyl)aniline

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide Reflux;	88%

N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) + N-butylamine (109-73-9) → 1-trityl-5-(4'-butylaminomethyl-1,1'-biphenyl-2-yl)-1H-tetrazole

Conditions	Yield
In tetrahydrofuran at 20℃; for 3h;	88%
In tetrahydrofuran at 20℃; for 2h;	80%

N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → 5-(4'-(chloromethyl)-[1,1'-biphenyl]-2-yl)-1H-tetrazole

Conditions	Yield
With hydrogenchloride In water; ethyl acetate at 80℃; for 15h; Temperature; Solvent;	88%

N-(4-methoxy)benzyl-4-methyl-2-n-propyl-1H-benzimidazole-6-carboxamide (1239196-65-6) + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → N-(4-methoxy)benzyl-1-([2'-(1-triphenylmethyltetrazol-5-yl)-(1,1'-biphenyl)-4-yl]methyl)-4-methyl-2-n-propyl-1H-benzimidazole-6-carboxamide (1390645-41-6)

Conditions	Yield
Stage #1: N-(4-methoxy)benzyl-4-methyl-2-n-propyl-1H-benzimidazole-6-carboxamide With potassium tert-butylate In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole In N,N-dimethyl-formamide at 0 - 25℃; for 12h;	87.7%

Upstream product

• 124750-53-4 N-triphenylmethyl-5-(4'-methylbiphenyl-2-yl)tetrazole 
• 611-20-1 salicylonitrile 
• 624-31-7 4-tolyl iodide 
• 2042-37-7 o-cyanobromobenzene 
• 114772-53-1 2-Cyano-4'-methylbiphenyl 
• 76-83-5 trityl chloride 
• 138313-23-2 2-<(trifluoromethanesulfonyl)oxy>benzonitrile 
• 120568-11-8 2-(tetrazol-5-yl)-4'-methyl-1,1'-biphenyl 
• 31614-66-1 tributyl(p-tolyl)stannane 
• 5720-05-8 4-methylphenylboronic acid 
• 7148-03-0 o-tolylbenzoic acid 
• 114772-35-9 4'-methylbiphenyl-2-carboxylic acid chloride 
• 120568-15-2 N-(2-cyanoethyl)-4'-methyl[1,1']biphenyl-2-carboxamide 
• 120568-17-4 5-<4'-Methyl-1,1'-biphenyl-2-yl>-1H-tetrazole-1-propanenitrile 

Downstream Products

• 144757-33-5 methyl α-(1-oxopentyl)-2'-<1-(triphenylmethyl)-1H-tetrazol-5-yl><1,1'-biphenyl>-4-propanoate 
• 194417-17-9 1-[2'-(1-triphenylmethyl-1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-1H-benzotriazole 
• 194417-18-0 1-[2'-(1-triphenylmethyl-1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-1H-naphtho[2,3-d][1,2,3]triazole 
• 162126-55-8 (R)-2-(t-Butoxycarbonylamino)-N-phenyl-N-[[2'-(N-triphenylmethyl-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl]methyl]butanamide 
• 956466-83-4 C₄₄H₄₂N₆O₂Se 
• 956466-91-4 C₄₉H₄₄N₆O₂Se 
• 169954-71-6 [1,1-Dimethyl-2-(3-{(R)-2-oxo-1-[2'-(1-trityl-1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-2,3,4,5-tetrahydro-1H-benzo[b]azepin-3-yl}-ureido)-ethyl]-carbamic acid tert-butyl ester 

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