Product Name

  • Name

    Irbesartan

  • EINECS 604-078-2
  • CAS No. 138402-11-6
  • Article Data57
  • CAS DataBase
  • Density 1.3 g/cm3
  • Solubility
  • Melting Point 180-181 °C
  • Formula C25H28N6O
  • Boiling Point 648.6 °C at 760 mmHg
  • Molecular Weight 428.537
  • Flash Point 346 °C
  • Transport Information
  • Appearance white crystalline powder
  • Safety 26
  • Risk Codes 22
  • Molecular Structure Molecular Structure of 138402-11-6 (Irbesartan)
  • Hazard Symbols HarmfulXn
  • Synonyms BMS 186295;SR 47436;2-Butyl-3-(p-(o-1H-tetrazol-5-ylphenyl)benzyl)-1,3-diazaspiro(4.4)non-1-en-4-one;1,3-Diazaspiro[4.4]non-1-en-4-one,2-butyl- 3-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]- methyl]-;Avapro;3-byty1-3-[p-(0-1H-tetrazol-5-y1-pheny1)benzy1],3-diazospiro[4,4]non-1-en-4-ketone;Aprovel;138402-11-6;Irbesartan (JAN/USAN);Avapro (TN);
  • PSA 87.13000
  • LogP 4.15090

Synthetic route

3-{[2′-(1-benzyl-1H-tetrazol-5-yl)-1,1′-biphenyl-4-yl]methyl}-2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one

3-{[2′-(1-benzyl-1H-tetrazol-5-yl)-1,1′-biphenyl-4-yl]methyl}-2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one
138402-11-6

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

Conditions
ConditionsYield
With 5% palladium on barium sulphate; ammonium formate In water; isopropyl alcohol at 25 - 55℃; for 3.5h;100%
In water; isopropyl alcohol at 55℃; for 6h;96%
With 5% palladium on barium sulphate; ammonium formate In water; isopropyl alcohol at 55℃; for 3.5h; Time;0.091 g
trityl irbesartan
138402-10-5

trityl irbesartan

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one
138402-11-6

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

Conditions
ConditionsYield
Stage #1: trityl irbesartan With hydrogenchloride In water; acetone at 35 - 45℃; for 1.5 - 2h;
Stage #2: In water; acetone at 15℃; pH=11 - 13; Alkaline aqueous solution;		98.75%
With sulfuric acid In water; acetone at 35 - 40℃; for 7h;93%
With sodium hydroxide In methanol at 20℃;87%
4'-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-[1,1'-biphenyl]-2-carbonitrile
138401-24-8

4'-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-[1,1'-biphenyl]-2-carbonitrile

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one
138402-11-6

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

Conditions
ConditionsYield
With sodium azide; tributyltin chloride In o-xylene Heating;95%
With sodium azide; triethylamine hydrochloride In toluene at 100℃; for 24h; Solvent; Temperature; Large scale;90%
With trimethylsilylazide; tetrabutyl ammonium fluoride In water; N,N-dimethyl-formamide at 120℃; for 36h;89%
N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole
124750-51-2

N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole

2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one hydrochloride

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

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

Conditions
ConditionsYield
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;
trityl irbesartan
138402-10-5

trityl irbesartan

A

methoxytriphenylmethane
596-31-6

methoxytriphenylmethane

B

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one
138402-11-6

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

Conditions
ConditionsYield
Stage #1: trityl irbesartan With hydroxylamine hydrochloride In methanol; water; acetone at 20℃; for 2h;
Stage #2: With sodium hydroxide In methanol; water; acetone at 20 - 25℃; pH=3.8 - 12.5;		A n/a
B 91%
Stage #1: trityl irbesartan With hydroxylamine hydrochloride In methanol; water; isopropyl alcohol; acetone at 20℃; for 2h;
Stage #2: With sodium hydroxide In methanol; water; acetone at 20 - 25℃; pH=12.0 - 12.5;		A n/a
B 89%
1-pentanoylamino-cyclopentanecarboxylic acid (2'-cyano-biphenyl-4-ylmethyl)-amide
141745-71-3

1-pentanoylamino-cyclopentanecarboxylic acid (2'-cyano-biphenyl-4-ylmethyl)-amide

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one
138402-11-6

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

Conditions
ConditionsYield
Stage #1: 1-pentanoylamino-cyclopentanecarboxylic acid (2'-cyano-biphenyl-4-ylmethyl)-amide With sodium azide; tributyltin chloride; N,N-dimethyl-formamide In o-xylene at 15 - 155℃; for 1h;
Stage #2: With hydrogenchloride In dichloromethane; o-xylene; water at 20℃; for 1h; Product distribution / selectivity;		90%
With sodium azide; tributyltin chloride; N,N-dimethyl-formamide In o-xylene at 150 - 155℃; for 20h;71%
Multi-step reaction with 2 steps
1: 81 percent / trifluoro acetic acid / toluene / Heating
2: 95 percent / tributyl tin chloride; sodium azide / o-xylene / Heating
View Scheme
4-[(α-N-pentanoylamino)cyclopentamidomethyl]-2'-carboxamidobiphenyl
945540-18-1

4-[(α-N-pentanoylamino)cyclopentamidomethyl]-2'-carboxamidobiphenyl

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one
138402-11-6

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

Conditions
ConditionsYield
Stage #1: 4-[(α-N-pentanoylamino)cyclopentamidomethyl]-2'-carboxamidobiphenyl With sodium azide; tributyltin chloride; N,N-dimethyl-formamide In o-xylene at 15 - 155℃; for 1h;
Stage #2: With hydrogenchloride In dichloromethane; o-xylene; water at 20 - 25℃; for 1.5h; Product distribution / selectivity;		88.5%
With sodium azide; tributyltin chloride; N,N-dimethyl-formamide for 50h;65%
Multi-step reaction with 2 steps
1: 65 percent / trifluoroacetic acid / o-xylene / 17 h / Heating
2: 80 percent / sodium azide; tributyltin chloride; DMF / o-xylene / 40 h / 150 - 155 °C
View Scheme
Multi-step reaction with 2 steps
1.1: trifluoroacetic acid / o-xylene / 15 h / 25 - 140 °C
1.2: 0.17 h / 25 - 30 °C / pH 9
2.1: sodium azide; tributyltin chloride / o-xylene / 25 °C / Heating / reflux
2.2: 2.25 h / 20 - 25 °C
2.3: 2 h / 20 - 25 °C / pH 4.5 - 4.8
View Scheme
Multi-step reaction with 3 steps
1.1: trifluoroacetic acid / o-xylene / 15 h / 25 - 140 °C
1.2: 0.17 h / 25 - 30 °C / pH 9
2.1: pyridine; p-toluenesulfonyl chloride / 1 h / 70 - 75 °C
3.1: sodium azide; tributyltin chloride / o-xylene / 60 h / 25 - 137 °C
3.2: 1 h / 10 - 15 °C / pH 11.5 - 12
3.3: 10 - 30 °C / pH 4.6 - 4.8
View Scheme
3-[4-bromobenzyl]-2-n-butyl-1,3-diazaspiro[4.4]non-1-en-4-one
731851-41-5

3-[4-bromobenzyl]-2-n-butyl-1,3-diazaspiro[4.4]non-1-en-4-one

2-(N-triphenylmethyl-tetrazol-5-yl)-phenylboronic acid
144873-97-2

2-(N-triphenylmethyl-tetrazol-5-yl)-phenylboronic acid

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one
138402-11-6

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

Conditions
ConditionsYield
With potassium hydroxide; tetrakis(triphenylphosphine) palladium(0) In methanol for 10h; Suzuki coupling; Heating;84%
Stage #1: 3-[4-bromobenzyl]-2-n-butyl-1,3-diazaspiro[4.4]non-1-en-4-one; 2-(N-triphenylmethyl-tetrazol-5-yl)-phenylboronic acid With potassium carbonate; tetrakis(triphenylphosphine) palladium(0) In water; toluene at 25 - 85℃; for 0.5h;
Stage #2: With hydrogenchloride In water; 4-methyl-2-pentanone Product distribution / selectivity;		22%
3-[2'-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-2-thiophen-2-yl-1,3-diaza-spiro[4.4]non-1-en-4-one
1199814-92-0

3-[2'-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-2-thiophen-2-yl-1,3-diaza-spiro[4.4]non-1-en-4-one

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one
138402-11-6

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

Conditions
ConditionsYield
With hydrogen; Raney nickel In methanol at 20℃;84%
1-[(2'-carboxamidobiphenyl-4-yl)methyl]-2-n-butyl-4-spirocyclopentane-2-imidazolin-5-one
144625-34-3

1-[(2'-carboxamidobiphenyl-4-yl)methyl]-2-n-butyl-4-spirocyclopentane-2-imidazolin-5-one

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one
138402-11-6

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

Conditions
ConditionsYield
With sodium azide; tributyltin chloride; N,N-dimethyl-formamide In o-xylene at 150 - 155℃; for 40h;80%
Stage #1: 1-[(2'-carboxamidobiphenyl-4-yl)methyl]-2-n-butyl-4-spirocyclopentane-2-imidazolin-5-one With sodium azide; tributyltin chloride In o-xylene at 25℃; Heating / reflux;
Stage #2: With hydrogenchloride In dichloromethane; o-xylene; water at 20 - 25℃; for 2.25h;
Stage #3: With ammonia In dichloromethane; o-xylene; water at 20 - 25℃; for 2h; pH=4.5 - 4.8; Product distribution / selectivity;		77%
4'-(bromomethyl)-1,1'-biphenyl-2-carbonitrile
114772-54-2

4'-(bromomethyl)-1,1'-biphenyl-2-carbonitrile

2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one hydrochloride

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

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

Conditions
ConditionsYield
Stage #1: 2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one hydrochloride With potassium carbonate; tetrabutylammomium bromide In water at 25 - 60℃;
Stage #2: 4'-(bromomethyl)-1,1'-biphenyl-2-carbonitrile In water at 55 - 60℃;
Stage #3: With sodium azide; triethylamine hydrochloride In toluene at 25 - 105℃; Product distribution / selectivity;		79%
methanol
67-56-1

methanol

trityl irbesartan
138402-10-5

trityl irbesartan

A

methoxytriphenylmethane
596-31-6

methoxytriphenylmethane

B

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one
138402-11-6

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

Conditions
ConditionsYield
for 10h; Heating / reflux;A 73%
B 71%
...Expand
N-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]amine hydrochloride

N-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]amine hydrochloride

2-butyl-3-oxa-1-aza-spiro[4.4]non-1-en-4-one
15026-81-0

2-butyl-3-oxa-1-aza-spiro[4.4]non-1-en-4-one

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one
138402-11-6

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

Conditions
ConditionsYield
With methanesulfonic acid In 1-methyl-pyrrolidin-2-one at 160℃; under 150.015 Torr; for 2.5h; Product distribution / selectivity;70.5%
In 1-methyl-pyrrolidin-2-one at 140℃; under 150.015 Torr; for 5h; Product distribution / selectivity;60.4%
2-n-butyl-3-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1,3-diazaspiro[4.4]non-1-en-4-one hydrobromide
329055-24-5

2-n-butyl-3-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1,3-diazaspiro[4.4]non-1-en-4-one hydrobromide

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one
138402-11-6

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

Conditions
ConditionsYield
In ethanol; dichloromethane; water Product distribution / selectivity; Heating / reflux;
2-butyl-3-{2'-[2-(1-methyl-1-phenyl-ethyl)-2H-tetrazol-5-yl]-biphenyl-4-ylmethyl}-1,3-diaza-spiro[4.4]non-1-en-4-one
852357-70-1

2-butyl-3-{2'-[2-(1-methyl-1-phenyl-ethyl)-2H-tetrazol-5-yl]-biphenyl-4-ylmethyl}-1,3-diaza-spiro[4.4]non-1-en-4-one

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one
138402-11-6

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

Conditions
ConditionsYield
Stage #1: 2-butyl-3-{2'-[2-(1-methyl-1-phenyl-ethyl)-2H-tetrazol-5-yl]-biphenyl-4-ylmethyl}-1,3-diaza-spiro[4.4]non-1-en-4-one With hydrogenchloride; water In toluene at 15 - 20℃; for 4h;
Stage #2: With sodium acetate In water
1-cyano-1-n-pentanoylaminocyclopentane
194984-24-2

1-cyano-1-n-pentanoylaminocyclopentane

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one
138402-11-6

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1: 654 g / aq. hydrochloric acid / 2 h / 55 - 60 °C
2: 93 percent / dicyclohexylcarbodiimide; 1-hydroxybenzotriazole; diisopropylethylamine / CH2Cl2 / 7 h / 38 - 41 °C
3: 71 percent / sodium azide; tributyltin chloride; N,N-dimethylformamide / o-xylene / 20 h / 150 - 155 °C
View Scheme
N-pentanoylaminocyclopentane-1-carboxylic acid
15026-80-9

N-pentanoylaminocyclopentane-1-carboxylic acid

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one
138402-11-6

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: 93 percent / dicyclohexylcarbodiimide; 1-hydroxybenzotriazole; diisopropylethylamine / CH2Cl2 / 7 h / 38 - 41 °C
2: 71 percent / sodium azide; tributyltin chloride; N,N-dimethylformamide / o-xylene / 20 h / 150 - 155 °C
View Scheme
Multi-step reaction with 3 steps
1: 90 percent / dicyclohexylcarbodiimide; N-hydroxybenzotriazole; diisopropylethylamine / CH2Cl2 / 4.5 h / Heating
2: 65 percent / trifluoroacetic acid / o-xylene / 17 h / Heating
3: 80 percent / sodium azide; tributyltin chloride; DMF / o-xylene / 40 h / 150 - 155 °C
View Scheme
Multi-step reaction with 2 steps
1: 90 percent / dicyclohexylcarbodiimide; N-hydroxybenzotriazole; diisopropylethylamine / CH2Cl2 / 4.5 h / Heating
2: 65 percent / sodium azide; tributyltin chloride; DMF / 50 h
View Scheme
n-valeryl chloride
638-29-9

n-valeryl chloride

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one
138402-11-6

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

Conditions
ConditionsYield
Multi-step reaction with 4 steps
1: triethylamine / CH2Cl2 / 2.67 h / 0 - 5 °C
2: 654 g / aq. hydrochloric acid / 2 h / 55 - 60 °C
3: 93 percent / dicyclohexylcarbodiimide; 1-hydroxybenzotriazole; diisopropylethylamine / CH2Cl2 / 7 h / 38 - 41 °C
4: 71 percent / sodium azide; tributyltin chloride; N,N-dimethylformamide / o-xylene / 20 h / 150 - 155 °C
View Scheme
Multi-step reaction with 4 steps
1: 82 percent / sodium hydroxide / H2O; toluene / 2 h / 0 - 10 °C
2: 96 percent / 1-hydroxybenzotriazole; dicyclohexyl carbodiimide / CH2Cl2 / 25 - 35 °C
3: 81 percent / trifluoro acetic acid / toluene / Heating
4: 95 percent / tributyl tin chloride; sodium azide / o-xylene / Heating
View Scheme
1-aminocyclopentanecarbonitrile hydrochloride

1-aminocyclopentanecarbonitrile 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

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

Conditions
ConditionsYield
Multi-step reaction with 4 steps
1: triethylamine / CH2Cl2 / 2.67 h / 0 - 5 °C
2: 654 g / aq. hydrochloric acid / 2 h / 55 - 60 °C
3: 93 percent / dicyclohexylcarbodiimide; 1-hydroxybenzotriazole; diisopropylethylamine / CH2Cl2 / 7 h / 38 - 41 °C
4: 71 percent / sodium azide; tributyltin chloride; N,N-dimethylformamide / o-xylene / 20 h / 150 - 155 °C
View Scheme
2-(4-aminomethylphenyl)benzamide hydrochloride

2-(4-aminomethylphenyl)benzamide 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

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1: 90 percent / dicyclohexylcarbodiimide; N-hydroxybenzotriazole; diisopropylethylamine / CH2Cl2 / 4.5 h / Heating
2: 65 percent / trifluoroacetic acid / o-xylene / 17 h / Heating
3: 80 percent / sodium azide; tributyltin chloride; DMF / o-xylene / 40 h / 150 - 155 °C
View Scheme
Multi-step reaction with 2 steps
1: 90 percent / dicyclohexylcarbodiimide; N-hydroxybenzotriazole; diisopropylethylamine / CH2Cl2 / 4.5 h / Heating
2: 65 percent / sodium azide; tributyltin chloride; DMF / 50 h
View Scheme
Multi-step reaction with 2 steps
1.1: benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine; dicyclohexyl-carbodiimide / dichloromethane / 6 h / 25 - 33 °C
2.1: sodium azide; tributyltin chloride; N,N-dimethyl-formamide / o-xylene / 1 h / 15 - 155 °C
2.2: 1.5 h / 20 - 25 °C
View Scheme
Multi-step reaction with 3 steps
1.1: benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine; dicyclohexyl-carbodiimide / dichloromethane / 6 h / 25 - 33 °C
2.1: trifluoroacetic acid / o-xylene / 15 h / 25 - 140 °C
2.2: 0.17 h / 25 - 30 °C / pH 9
3.1: sodium azide; tributyltin chloride / o-xylene / 25 °C / Heating / reflux
3.2: 2.25 h / 20 - 25 °C
3.3: 2 h / 20 - 25 °C / pH 4.5 - 4.8
View Scheme
Multi-step reaction with 4 steps
1.1: benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine; dicyclohexyl-carbodiimide / dichloromethane / 6 h / 25 - 33 °C
2.1: trifluoroacetic acid / o-xylene / 15 h / 25 - 140 °C
2.2: 0.17 h / 25 - 30 °C / pH 9
3.1: pyridine; p-toluenesulfonyl chloride / 1 h / 70 - 75 °C
4.1: sodium azide; tributyltin chloride / o-xylene / 60 h / 25 - 137 °C
4.2: 1 h / 10 - 15 °C / pH 11.5 - 12
4.3: 10 - 30 °C / pH 4.6 - 4.8
View Scheme
[(2'-cyanobiphenyl-4-yl)methyl]amine
133690-92-3

[(2'-cyanobiphenyl-4-yl)methyl]amine

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one
138402-11-6

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1: 96 percent / 1-hydroxybenzotriazole; dicyclohexyl carbodiimide / CH2Cl2 / 25 - 35 °C
2: 81 percent / trifluoro acetic acid / toluene / Heating
3: 95 percent / tributyl tin chloride; sodium azide / o-xylene / Heating
View Scheme
Multi-step reaction with 2 steps
1.1: triphenyl phosphate / pyridine / 0.17 h / 150 °C / microwave irradiation
1.2: 75 percent / pyridine / 0.17 h / 250 °C / 7500.6 Torr / microwave irradiation
2.1: 73 percent / tri-n-butyltin chloride; sodium azide; tetrabutylammonium bromide / dimethylformamide / 1 h / 220 °C / 6000.48 Torr / microwave irradiation
View Scheme
Multi-step reaction with 3 steps
1.1: potassium hydroxide; tert-butyl alcohol / 70 - 75 °C
1.2: 1 h / 2 - 5 °C / pH 1.2 - 1.4
2.1: benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine; dicyclohexyl-carbodiimide / dichloromethane / 6 h / 25 - 33 °C
3.1: sodium azide; tributyltin chloride; N,N-dimethyl-formamide / o-xylene / 1 h / 15 - 155 °C
3.2: 1.5 h / 20 - 25 °C
View Scheme
Multi-step reaction with 4 steps
1.1: potassium hydroxide; tert-butyl alcohol / 70 - 75 °C
1.2: 1 h / 2 - 5 °C / pH 1.2 - 1.4
2.1: benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine; dicyclohexyl-carbodiimide / dichloromethane / 6 h / 25 - 33 °C
3.1: trifluoroacetic acid / o-xylene / 15 h / 25 - 140 °C
3.2: 0.17 h / 25 - 30 °C / pH 9
4.1: sodium azide; tributyltin chloride / o-xylene / 25 °C / Heating / reflux
4.2: 2.25 h / 20 - 25 °C
4.3: 2 h / 20 - 25 °C / pH 4.5 - 4.8
View Scheme
Multi-step reaction with 5 steps
1.1: potassium hydroxide; tert-butyl alcohol / 70 - 75 °C
1.2: 1 h / 2 - 5 °C / pH 1.2 - 1.4
2.1: benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine; dicyclohexyl-carbodiimide / dichloromethane / 6 h / 25 - 33 °C
3.1: trifluoroacetic acid / o-xylene / 15 h / 25 - 140 °C
3.2: 0.17 h / 25 - 30 °C / pH 9
4.1: pyridine; p-toluenesulfonyl chloride / 1 h / 70 - 75 °C
5.1: sodium azide; tributyltin chloride / o-xylene / 60 h / 25 - 137 °C
5.2: 1 h / 10 - 15 °C / pH 11.5 - 12
5.3: 10 - 30 °C / pH 4.6 - 4.8
View Scheme
1-amino-1-cyclopentanecarboxylic acid
52-52-8

1-amino-1-cyclopentanecarboxylic acid

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one
138402-11-6

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

Conditions
ConditionsYield
Multi-step reaction with 4 steps
1: 82 percent / sodium hydroxide / H2O; toluene / 2 h / 0 - 10 °C
2: 96 percent / 1-hydroxybenzotriazole; dicyclohexyl carbodiimide / CH2Cl2 / 25 - 35 °C
3: 81 percent / trifluoro acetic acid / toluene / Heating
4: 95 percent / tributyl tin chloride; sodium azide / o-xylene / Heating
View Scheme
(2'-cyano-biphenyl-4-ylmethyl)-carbamic acid tert-butyl ester

(2'-cyano-biphenyl-4-ylmethyl)-carbamic acid tert-butyl ester

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one
138402-11-6

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: 71 percent / triphenyl phosphate / pyridine / 0.17 h / 250 °C / 11250.9 Torr
2: 73 percent / tri-n-butyltin chloride; sodium azide; tetrabutylammonium bromide / dimethylformamide / 1 h / 220 °C / 6000.48 Torr / microwave irradiation
View Scheme
cycloleucine methyl ester hydrochloride
60421-23-0

cycloleucine methyl ester 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

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: 71 percent / triphenyl phosphate / pyridine / 0.17 h / 250 °C / 11250.9 Torr
2: 73 percent / tri-n-butyltin chloride; sodium azide; tetrabutylammonium bromide / dimethylformamide / 1 h / 220 °C / 6000.48 Torr / microwave irradiation
View Scheme
Multi-step reaction with 2 steps
1.1: triphenyl phosphate / pyridine / 0.17 h / 150 °C / microwave irradiation
1.2: 75 percent / pyridine / 0.17 h / 250 °C / 7500.6 Torr / microwave irradiation
2.1: 73 percent / tri-n-butyltin chloride; sodium azide; tetrabutylammonium bromide / dimethylformamide / 1 h / 220 °C / 6000.48 Torr / microwave irradiation
View Scheme
valeric acid
109-52-4

valeric acid

Phenylmagnesium halide

Phenylmagnesium halide

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one
138402-11-6

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1.1: triphenyl phosphate / pyridine / 0.17 h / 150 °C / microwave irradiation
1.2: 75 percent / pyridine / 0.17 h / 250 °C / 7500.6 Torr / microwave irradiation
2.1: 73 percent / tri-n-butyltin chloride; sodium azide; tetrabutylammonium bromide / dimethylformamide / 1 h / 220 °C / 6000.48 Torr / microwave irradiation
View Scheme
1-bromomethyl-4-bromobenzene
589-15-1

1-bromomethyl-4-bromobenzene

4-bromo-2.2.3.3-tetramethyl-bicyclo-<0.1.2>-pentanol-(1)-one-(5)

4-bromo-2.2.3.3-tetramethyl-bicyclo-<0.1.2>-pentanol-(1)-one-(5)

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one
138402-11-6

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: 94.6 percent / K2CO3 / dimethylformamide / 8 h / 25 - 35 °C
2: 84 percent / potassium hydroxide; Pd(PPh3)4 / methanol / 10 h / Heating
View Scheme
2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one hydrochloride

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

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: 94.6 percent / K2CO3 / dimethylformamide / 8 h / 25 - 35 °C
2: 84 percent / potassium hydroxide; Pd(PPh3)4 / methanol / 10 h / Heating
View Scheme
ethyl 1-aminocyclopentanecarboxylate
1664-35-3

ethyl 1-aminocyclopentanecarboxylate

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one
138402-11-6

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1: 96 percent / AcOH / xylene / 6.5 h / Heating
2: 1.) NaH / 1.) DMF, RT, 0.5 h, 2.) DMF, RT, 1 h
3: 68 percent / Bu3SnN3 / xylene / 88 h / Heating
View Scheme
4'-(bromomethyl)-1,1'-biphenyl-2-carbonitrile
114772-54-2

4'-(bromomethyl)-1,1'-biphenyl-2-carbonitrile

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one
138402-11-6

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: 1.) NaH / 1.) DMF, RT, 0.5 h, 2.) DMF, RT, 1 h
2: 68 percent / Bu3SnN3 / xylene / 88 h / Heating
View Scheme
potassium hydroxide
1310-58-3

potassium hydroxide

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one
138402-11-6

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

irbesartan potassium

irbesartan potassium

Conditions
ConditionsYield
In ipa at 50℃; for 1.58333h; Heating / reflux;89%
In ipa at 50℃; for 1.5h; Heating / reflux;51.4%
copper(II) choride dihydrate

copper(II) choride dihydrate

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one
138402-11-6

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

[Cu(irbesartan)2(H2O)]

[Cu(irbesartan)2(H2O)]

Conditions
ConditionsYield
With sodium hydroxide In ethanol pH=6;85%
sodium hydroxide
1310-73-2

sodium hydroxide

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one
138402-11-6

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

irbesartan sodium

irbesartan sodium

Conditions
ConditionsYield
In ipa at 60℃; for 2.5h; Heating / reflux;66%
In water Product distribution / selectivity;
(3R,4S,5S,6S)-2-bromo-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate
57820-69-6

(3R,4S,5S,6S)-2-bromo-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one
138402-11-6

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

A

(2S,3S,4S,5R,6R)-3,4,5-Triacetoxy-6-{5-[4'-(2-butyl-4-oxo-1,3-diaza-spiro[4.4]non-1-en-3-ylmethyl)-biphenyl-2-yl]-tetrazol-1-yl}-tetrahydro-pyran-2-carboxylic acid methyl ester

(2S,3S,4S,5R,6R)-3,4,5-Triacetoxy-6-{5-[4'-(2-butyl-4-oxo-1,3-diaza-spiro[4.4]non-1-en-3-ylmethyl)-biphenyl-2-yl]-tetrazol-1-yl}-tetrahydro-pyran-2-carboxylic acid methyl ester

B

(2S,3S,4S,5R,6R)-3,4,5-Triacetoxy-6-{5-[4'-(2-butyl-4-oxo-1,3-diaza-spiro[4.4]non-1-en-3-ylmethyl)-biphenyl-2-yl]-tetrazol-2-yl}-tetrahydro-pyran-2-carboxylic acid methyl ester

(2S,3S,4S,5R,6R)-3,4,5-Triacetoxy-6-{5-[4'-(2-butyl-4-oxo-1,3-diaza-spiro[4.4]non-1-en-3-ylmethyl)-biphenyl-2-yl]-tetrazol-2-yl}-tetrahydro-pyran-2-carboxylic acid methyl ester

Conditions
ConditionsYield
With silver carbonate In toluene at 100℃; for 18h; protection from light;A 30%
B 59%
...Expand
methanol
67-56-1

methanol

water
7732-18-5

water

silver nitrate

silver nitrate

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one
138402-11-6

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

[Ag2(2-butyl-3-[p-(o-(1H-tetrazol-5-yl)phenyl)benzyl]-1,3-diazospiro[4.4]non-1-en-4-one(-H))2]*methanol*0.17water

[Ag2(2-butyl-3-[p-(o-(1H-tetrazol-5-yl)phenyl)benzyl]-1,3-diazospiro[4.4]non-1-en-4-one(-H))2]*methanol*0.17water

Conditions
ConditionsYield
In methanol; water; acetonitrile mixing CH3CN soln. of silver compd., water and methanolic soln. of tetrazole deriv., keeping at room temp. in dark with slow evapn.; isolation of crystals, elem. anal.;56%
...Expand
2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one
138402-11-6

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

methyl iodide
74-88-4

methyl iodide

A

2-n-butyl-3-<<2'-(2-methyltetrazol-5-yl)biphenyl-4-yl>methyl>-1,3-diazaspiro<4.4>non-1-en-4-one

2-n-butyl-3-<<2'-(2-methyltetrazol-5-yl)biphenyl-4-yl>methyl>-1,3-diazaspiro<4.4>non-1-en-4-one

B

2-n-butyl-3-<<2'-(1-methyltetrazol-5-yl)biphenyl-4-yl>methyl>-1,3-diazaspiro<4.4>non-1-en-4-one

2-n-butyl-3-<<2'-(1-methyltetrazol-5-yl)biphenyl-4-yl>methyl>-1,3-diazaspiro<4.4>non-1-en-4-one

Conditions
ConditionsYield
With sodium hydride 1.) DMF, RT, 0.5 h, 2.) DMF, RT, 4 h; Yield given. Multistep reaction. Yields of byproduct given;
...Expand
2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one
138402-11-6

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

2-(tetrazol-5-yl)-4'-methyl-1,1'-biphenyl
120568-11-8

2-(tetrazol-5-yl)-4'-methyl-1,1'-biphenyl

Conditions
ConditionsYield
In phosphate buffer at 37℃; pH=7.40; Kinetics; Further Variations:; Solvents; Temperatures; pH-values;
2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one
138402-11-6

2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one

4-{4-oxo-3-[2'-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-1,3-diaza-spiro[4.4]non-1-en-2-yl}-butyric acid

4-{4-oxo-3-[2'-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-1,3-diaza-spiro[4.4]non-1-en-2-yl}-butyric acid

Conditions
ConditionsYield
With potassium iodate; potassium iodide In water; dimethyl sulfoxide at 30℃; Kinetics; Further Variations:; Temperatures; concentrations of reagents;

Irbesartan Chemical Properties

Molecular Structure of Irbesartan (CAS NO.138402-11-6):

IUPAC Name: 2-butyl-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]-1,3-diazaspiro[4.4]non-1-en-4-one 
Empirical Formula: C25H28N6O
Molecular Weight: 428.5294
H bond acceptors: 7
H bond donors: 1
Freely Rotating Bonds: 7
Polar Surface Area: 76.27 Å2
Index of Refraction: 1.689
Molar Refractivity: 125.44 cm3
Molar Volume: 328.2 cm3
Surface Tension: 54.4 dyne/cm
Density: 1.3 g/cm3
Flash Point: 346 °C
Enthalpy of Vaporization: 95.62 kJ/mol
Boiling Point: 648.6 °C at 760 mmHg
Vapour Pressure: 1.05E-16 mmHg at 25°C
Melting point: 180-181°C
InChI
InChI=1/C25H28N6O/c1-2-3-10-22-26-25(15-6-7-16-25)24(32)31(22)17-18-11-13-19(14-12-18)20-8-4-5-9-21(20)23-27-29-30-28-23/h4-5,8-9,11-14H,2-3,6-7,10,15-17H2,1H3,(H,27,28,29,30)
Smiles
C12(C(N(Cc3ccc(c4c(c5[nH]nnn5)cccc4)cc3)C(=N1)CCCC)=O)CCCC2
Product Categories: Active Pharmaceutical Ingredients; Antihypertensive; Hypertension; Inhibitors; Intermediates & Fine Chemicals; Pharmaceuticals; API's

Irbesartan Safety Profile

Hazard Codes: HarmfulXn
Risk Statements: 22
R22:Harmful if swallowed.
Safety Statements: 26
S26: In case of contact with eyes, rinse immediately with plenty of water and seek medical advice.

Irbesartan Specification

  Irbesartan , with CAS number of 138402-11-6, can be called 1,3-Diazaspiro(4.4)non-1-en-4-one, 2-butyl-3-((2-(1H-tetrazol-5-yl)(1,1-biphenyl)-4-yl)methyl)- ; 1,3-Diazaspiro[4.4]non-1-en-4-one,2-butyl- 3-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]- methyl]- ; Avapro ; 3-byty1-3-[p-(0-1H-tetrazol-5-y1-pheny1)benzy1],3-diazospiro[4,4]non-1-en-4-ketone ; 2-Butyl-3-(p-(o-1H-tetrazol-5-ylphenyl)benzyl)-1,3-diazaspiro(4.4)non-1-en-4-one . It is a crystalline solid, used as an angiotensin II type 1 (AII1)-receptor antagonist. Irbesartan is also available in a combination formulation with a low dose thiazide diuretic, invariably Hydrochlorothiazide, to achieve an additive antihypertensive effect.

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