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CAS 147403-52-9

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

Codes: AZILS-008, AZILS-023a, AZIL-009

Application context (from source-drug indications)

HypertensionAzilsartanEssential hypertensionAzilsartanType 2 diabetesAzilsartanObesityAzilsartanDiabetesAzilsartanHypertensionAzilsartan Medoxomil Potassium/ChlorthalidoneEssential hypertensionAzilsartan Medoxomil Potassium/ChlorthalidoneEssential hypertensionAzilsartan Medoxomil PotassiumHypertensionAzilsartan Medoxomil Potassium

Source drugs (routes using this intermediate)

DrugTierExpiry
AzilsartanTier C — Watch / trade-
Azilsartan Medoxomil Potassium/ChlorthalidoneTier C — Watch / trade-
Azilsartan Medoxomil PotassiumTier C — Watch / trade-

Position in synthesis routes (up/downstream chain)

Ordered by route registration; left → right is the synthesis direction. The highlighted node is the current CAS; others link to their own profiles.

AzilsartanOriginator routesteps: 6total yield: 0.135 g
methyl 2-(((2'-cyano-[1,1'-biphenyl]-4-yl)methyl)amino)-3-nitrobenzoate→methyl 3-amino-2-(((2'-cyano-[1,1'-biphenyl]-4-yl)methyl)amino)benzoate→triethoxymethoxyethane→methyl 1-((2'-cyano-[1,1'-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate→methyl (Z)-2-ethoxy-1-((2'-(N'-hydroxycarbamimidoyl)-[1,1'-biphenyl]-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylate→ethyl carbonochloridate→methyl (Z)-2-ethoxy-1-((2'-(N'-((ethoxycarbonyl)oxy)carbamimidoyl)-[1,1'-biphenyl]-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylate→methyl 2-ethoxy-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)-[1,1'-biphenyl]-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylate
AzilsartanOptimised routesteps: 3total yield: 173.2 g
methyl 2-ethoxy-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)-[1,1'-biphenyl]-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylate→ethyl 1-((2'-cyano-[1,1'-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate→2,6-dichloro-9-((3S,4R,5R)-3-fluoro-4-((triisopropylsilyl)oxy)-5-(((triisopropylsilyl)oxy)methyl)tetrahydrofuran-2-yl)-9H-purine
AzilsartanOptimised routesteps: 4total yield: 9.5 g
AzilsartanOptimised routesteps: 5total yield: 13.5 g
4'-methyl-[1,1'-biphenyl]-2-carbonitrile→2,6-dichloro-9-((3S,4R,5R)-3-fluoro-4-((triisopropylsilyl)oxy)-5-(((triisopropylsilyl)oxy)methyl)tetrahydrofuran-2-yl)-9H-purine→3-(4'-methyl-[1,1'-biphenyl]-2-yl)-1,2,4-oxadiazol-5(4H)-one→3-(4'-(bromomethyl)-[1,1'-biphenyl]-2-yl)-1,2,4-oxadiazol-5(4H)-one→2,6-dichloro-9-((3S,4R,5R)-3-fluoro-4-((triisopropylsilyl)oxy)-5-(((triisopropylsilyl)oxy)methyl)tetrahydrofuran-2-yl)-9H-purine→ethyl 2-ethoxy-1H-benzo[d]imidazole-7-carboxylate→methyl 2-ethoxy-1H-benzo[d]imidazole-7-carboxylate→2,6-dichloro-9-((3S,4R,5R)-3-fluoro-4-((triisopropylsilyl)oxy)-5-(((triisopropylsilyl)oxy)methyl)tetrahydrofuran-2-yl)-9H-purine→2,6-dichloro-9-((3S,4R,5R)-3-fluoro-4-((triisopropylsilyl)oxy)-5-(((triisopropylsilyl)oxy)methyl)tetrahydrofuran-2-yl)-9H-purine→ethyl 2-ethoxy-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)-[1,1'-biphenyl]-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylate→methyl 2-ethoxy-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)-[1,1'-biphenyl]-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylate→2,6-dichloro-9-((3S,4R,5R)-3-fluoro-4-((triisopropylsilyl)oxy)-5-(((triisopropylsilyl)oxy)methyl)tetrahydrofuran-2-yl)-9H-purine
Azilsartan Medoxomil Potassium/ChlorthalidoneOptimised routesteps: 5total yield: 2.9 g
methyl 3-amino-2-(((2'-cyano-[1,1'-biphenyl]-4-yl)methyl)amino)benzoate→methyl 2-ethoxy-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)-[1,1'-biphenyl]-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylate→2,6-dichloro-9-((3S,4R,5R)-3-fluoro-4-((triisopropylsilyl)oxy)-5-(((triisopropylsilyl)oxy)methyl)tetrahydrofuran-2-yl)-9H-purine→methyl (Z)-3-amino-2-(((2'-(N'-((ethoxycarbonyl)oxy)carbamimidoyl)-[1,1'-biphenyl]-4-yl)methyl)amino)benzoate→methyl (Z)-2-ethoxy-1-((2'-(N'-((ethoxycarbonyl)oxy)carbamimidoyl)-[1,1'-biphenyl]-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylate
Azilsartan Medoxomil PotassiumOptimised routesteps: 5total yield: 2.9 g
methyl 3-amino-2-(((2'-cyano-[1,1'-biphenyl]-4-yl)methyl)amino)benzoate→methyl 2-ethoxy-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)-[1,1'-biphenyl]-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylate→2,6-dichloro-9-((3S,4R,5R)-3-fluoro-4-((triisopropylsilyl)oxy)-5-(((triisopropylsilyl)oxy)methyl)tetrahydrofuran-2-yl)-9H-purine→methyl (Z)-3-amino-2-(((2'-(N'-((ethoxycarbonyl)oxy)carbamimidoyl)-[1,1'-biphenyl]-4-yl)methyl)amino)benzoate→methyl (Z)-2-ethoxy-1-((2'-(N'-((ethoxycarbonyl)oxy)carbamimidoyl)-[1,1'-biphenyl]-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylate

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