138402-10-5

Basic information

• Product Name: Trityl Irbesartan
• Synonyms: TRITYL IRBESARTAN;TRIPHENYLMETHYL IRBESARTAN;2-butyl-3-[[4-[2-(2-trityl-tetrazol-5-yl)phenyl]phenyl]methyl]-1,3-diazaspiro[4.4]non-1-en-4-one;Trityl Irbestartan;2-N-BUTYL-4-SPIROCYCLOPENTANE-1-[(2'-(TRIPHENYL-METHYLTETRAZOL-5-YL)BIPHENYL-4-Y;TRIPHENYL IRBESARTAN;N-TriphenylMethyl Irbesartan;Irbesartan N1-Trityl IMpurity
• CAS NO: 138402-10-5
• Molecular Formula: C₄₄H₄₂N₆O
• Molecular Weight: 670.84
• EINECS: 1312995-182-4
• Product Categories: Irbesartan;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 138402-10-5.mol
• Article Data: 13

Chemical Properties

• Boiling Point: 834.612 °C at 760 mmHg
• Flash Point: 458.557 °C
• Appearance: White powder
• Density: 1.201 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.662
• Storage Temp.: Sealed in dry,Store in freezer, under -20°C
• PKA: 2.60±0.20(Predicted)
• CAS DataBase Reference: Trityl Irbesartan(CAS DataBase Reference)
• NIST Chemistry Reference: Trityl Irbesartan(138402-10-5)
• EPA Substance Registry System: Trityl Irbesartan(138402-10-5)

Safety Data

• Hazardous Substances Data: 138402-10-5(Hazardous Substances Data)

Usage

Uses

Irbesartan (I751000) derivative.

Uses

2-Butyl-3-((2''-(2-trityl-2H-tetrazol-5-yl)-[1,1''-biphenyl]-4-yl)methyl)-1,3-diazaspiro[4.4]non-1-en-4-one (CAS# 138402-10-5) is a useful building block, especially in the preparation of the antihypertensive drug, irbesartan.

InChI:InChI=1/C44H42N6O/c1-2-3-25-40-45-43(30-15-16-31-43)42(51)49(40)32-33-26-28-34(29-27-33)38-23-13-14-24-39(38)41-46-47-48-50(41)44(35-17-7-4-8-18-35,36-19-9-5-10-20-36)37-21-11-6-12-22-37/h4-14,17-24,26-29H,2-3,15-16,25,30-32H2,1H3

Synthetic route

3-[4-bromobenzyl]-2-n-butyl-1,3-diazaspiro[4.4]non-1-en-4-one (731851-41-5) → trityl irbesartan (138402-10-5)

Conditions	Yield
Stage #1: 2-(N-triphenylmethyl-tetrazol-5-yl)-phenylboronic acid; palladium diacetate; triphenylphosphine In tetrahydrofuran; 1,2-dimethoxyethane at 20℃; for 0.666667h; Stage #2: 3-[4-bromobenzyl]-2-n-butyl-1,3-diazaspiro[4.4]non-1-en-4-one With water; potassium carbonate In tetrahydrofuran; 1,2-dimethoxyethane at 20 - 80℃; for 3.5h; Heating / reflux;	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%

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) → trityl irbesartan (138402-10-5)

Conditions	Yield
With hydrogen; Raney nickel In N,N-dimethyl-formamide at 20℃;	88%

3-[4-bromobenzyl]-2-n-butyl-1,3-diazaspiro[4.4]non-1-en-4-one (731851-41-5) + 2-(N-triphenylmethyl-tetrazol-5-yl)-phenylboronic acid (144873-97-2) → trityl irbesartan (138402-10-5)

Conditions	Yield
With potassium carbonate; palladium diacetate; triphenylphosphine In water; toluene at 95 - 100℃; for 3 - 4h; Product distribution / selectivity;	80%
With caesium carbonate; palladium diacetate; triphenylphosphine In water; toluene at 95 - 100℃; for 3 - 4h; Product distribution / selectivity;	80%
With potassium hydroxide; palladium diacetate; triphenylphosphine In water; toluene at 95 - 100℃; for 3 - 4h; Product distribution / selectivity;	72%

N-pentanoylaminocyclopentane-1-carboxylic acid (15026-80-9) + 1-(2'-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl)methanamine (134603-82-0) → trityl irbesartan (138402-10-5)

Conditions	Yield
Stage #1: N-pentanoylaminocyclopentane-1-carboxylic acid; 1-(2'-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl)methanamine With methanesulfonic acid In toluene at 20℃; for 48h; Heating / reflux; Stage #2: With sodium hydroxide In water; ethyl acetate for 0.5h;	80%
Stage #1: N-pentanoylaminocyclopentane-1-carboxylic acid; 1-(2'-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl)methanamine With methanesulfonic acid In toluene at 20℃; for 48h; Heating / reflux; Stage #2: With sodium hydrogencarbonate In water; ethyl acetate for 0.5h;	80%

2-n-butyl-3-[4-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)benzyl]-1,3-diazaspiro[4.4]non-1-ene-4-one (894806-38-3) + N-trityl-5-(2-bromophenyl)tetrazole (143945-72-6) → trityl irbesartan (138402-10-5)

Conditions	Yield
Stage #1: With triphenylphosphine; palladium diacetate In tetrahydrofuran at 20℃; for 0.5h; Stage #2: 2-n-butyl-3-[4-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)benzyl]-1,3-diazaspiro[4.4]non-1-ene-4-one; N-trityl-5-(2-bromophenyl)tetrazole With potassium phosphate In tetrahydrofuran for 48h; Product distribution / selectivity; Heating / reflux;	54%
With potassium phosphate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride In tetrahydrofuran for 48h; Product distribution / selectivity; Heating / reflux;	32%

1-(1'-ethoxy)pentanaminylcyclopentent carboxylate (745814-10-2) + 1-(2'-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl)methanamine (134603-82-0) → trityl irbesartan (138402-10-5)

Conditions	Yield
acetic acid In toluene for 3h; Heating / reflux;	50%

4-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]phenylboronic acid (894806-37-2) + N-trityl-5-(2-bromophenyl)tetrazole (143945-72-6) → trityl irbesartan (138402-10-5)

Conditions	Yield
With potassium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride In water; ethyl acetate; N,N-dimethyl-formamide; toluene at 85℃; for 48h; Product distribution / selectivity;	50%
With sodium carbonate; tetrakis(triphenylphosphine) palladium(0) In ethanol; water; toluene for 5 - 6h; Suzuki Coupling; Heating / reflux;
With 1-(2,6-diisopropylphenyl)-3-(2-oxo-2-(2,4,6-tri-tert-butylphenylamino)ethyl)-1H-imidazol-3-ium bromide; palladium diacetate; potassium carbonate In water; N,N-dimethyl-formamide at 120℃; for 6h;

1-(pentanoylamino)cyclopentanecarboxamide (177219-40-8) + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → trityl irbesartan (138402-10-5)

Conditions	Yield
With sodium hydroxide; potassium carbonate; tetra(n-butyl)ammonium hydrogensulfate In toluene at 50 - 90℃; for 4h;	32%
With potassium hydroxide; tetra(n-butyl)ammonium hydrogensulfate In water; toluene at 90℃; for 1.5h;

C13H23NO3 (745814-11-3) + 1-(2'-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl)methanamine (134603-82-0) → trityl irbesartan (138402-10-5)

Conditions	Yield
Stage #1: C13H23NO3 With 2,6-dimethylpyridine; oxalyl dichloride In toluene at 0℃; for 1h; Stage #2: 1-(2'-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl)methanamine In toluene at 0 - 20℃; for 1h;	30%

N-pentanoyl-N-[[2'-[N-(triphenylmethyl)tetrazol-5-yl]-1,1'-biphenyl-4-yl]methyl]amine (439904-79-7) + ethyl 1-aminocyclopentanecarboxylate (1664-35-3) → trityl irbesartan (138402-10-5)

Conditions	Yield
Stage #1: N-pentanoyl-N-[[2'-[N-(triphenylmethyl)tetrazol-5-yl]-1,1'-biphenyl-4-yl]methyl]amine With 2,6-dimethylpyridine; oxalyl dichloride In toluene at 0℃; for 1h; Stage #2: ethyl 1-aminocyclopentanecarboxylate In toluene at 0 - 20℃; for 1h;	25%

2-(1-TRITYL-1H-TETRAZOL-5-YL)-4'-(1''-ETHOXYPENTANAMINYL)BIPHENYL (745814-08-8) + ethyl 1-aminocyclopentanecarboxylate (1664-35-3) → trityl irbesartan (138402-10-5)

Conditions	Yield
Stage #1: 2-(1-TRITYL-1H-TETRAZOL-5-YL)-4'-(1''-ETHOXYPENTANAMINYL)BIPHENYL; ethyl 1-aminocyclopentanecarboxylate In toluene at 20℃; for 2h; Stage #2: acetic acid In toluene for 5h; Heating / reflux;	20%

5-(4-(bromomethyl)-[1,1'-biphenyl]-2-yl]-1-(triphenylmethyl)-1H-tetrazole + 2-butyl-1,3-diaza-spiro[4.4]non-1-en-4one (138402-05-8) → trityl irbesartan (138402-10-5)

Conditions	Yield
With potassium hydroxide; tetrabutylammomium bromide In acetonitrile at 31 - 40℃; for 2.5h; Product distribution / selectivity;

trityl chloride (76-83-5) + 4'-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-[1,1'-biphenyl]-2-carbonitrile (138401-24-8) → trityl irbesartan (138402-10-5)

Conditions	Yield
Stage #1: 4'-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-[1,1'-biphenyl]-2-carbonitrile With tributyltin azide In xylene for 66h; Heating / reflux; Stage #2: trityl chloride With sodium hydroxide In tetrahydrofuran; dichloromethane; water for 26h;
Stage #1: 4'-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-[1,1'-biphenyl]-2-carbonitrile With sodium azide; tributyltin chloride; tetrabutylammomium bromide In toluene for 20h; Heating / reflux; Stage #2: With acetic acid In water; toluene at 20℃; for 0.25h; Stage #3: trityl chloride With triethylamine In dichloromethane at 25 - 30℃; for 2h;

trityl irbesartan (138402-10-5) → 2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one (138402-11-6)

Conditions	Yield
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%

trityl irbesartan (138402-10-5) → 2-n-butyl-4-spirocyclopentane-1-[(2'-(tetrazol-5-yl)biphenyl-4-yl)methyl]-2-imidazolin-5-one hydrochloride sesquihydrate

Conditions	Yield
With hydrogenchloride; water In toluene at 55℃; for 1h; Product distribution / selectivity;	95%

trityl irbesartan (138402-10-5) → methoxytriphenylmethane (596-31-6) + 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: 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%

methanol (67-56-1) + trityl irbesartan (138402-10-5) → methoxytriphenylmethane (596-31-6) + 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
for 10h; Heating / reflux;	A 73% B 71%

trityl irbesartan (138402-10-5) → 2-n-butyl-3-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1,3-diazaspiro[4.4]non-1-en-4-one hydrobromide (329055-24-5)

Conditions	Yield
With hydrogen bromide In ethanol; water at 20℃; for 3h;

trityl irbesartan (138402-10-5) → triphenylmethyl alcohol (76-84-6) + 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
With hydrogenchloride; water In acetone

trityl irbesartan (138402-10-5) → 2-n-butyl-4-spirocyclopentane-1-[((2'-tetrazol-5-yl)biphenyl-4-yl)methyl]-2-imidazolin-5-one hydrochloride (329055-23-4)

Conditions	Yield
Stage #1: trityl irbesartan With methanol; potassium hydroxide for 2.5h; Heating / reflux; Stage #2: With hydrogenchloride In water at 20℃; for 4h; pH=0.99; Product distribution / selectivity;
Stage #1: trityl irbesartan With methanol; toluene-4-sulfonic acid In thioguanin for 24h; Heating / reflux; Stage #2: With sodium hydroxide In water pH=12.7; Stage #3: With hydrogenchloride; sodium hydroxide Product distribution / selectivity; more than 3 stages;
With hydrogenchloride In ethanol; water at 20℃; for 3h; Product distribution / selectivity;

Upstream product

• 138402-05-8 2-N-BUTYL-1,3-DIAZA-SPIRO[4,4]NON-1-EN-4-ONE HYDROCHLORIDE 
• 138401-24-8 4'-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-(1,1'-biphenyl)-2-carbonitrile 
• 13840-05-6 NORSTRANDITE 
• 13840-04-5 AMMONIUM CERIUM(IV) SULFATE TETRAHYDRATE 
• 138400-06-3 3-(2-mercaptoethyl)quinazoline-2,4(1H,3H)-dione 
• 138399-44-7 ETHYL 2-(5-METHYLBENZO[D]OXAZOL-2-YL)ACETATE 
• 13839-92-4 3,3'-Diindolyl-2,2'-tetrasulfide 
• 138398-61-5 AMYLIN (8-37) (RAT) 
• 1383985-61-2 (1r,4r)-6'-bromo-4-methoxyspiro[cyclohexane-1,2'-inden]-1'(3'H)-imine hydrochloride 
• 13839-85-5 ytterbium(3+) nitrate hydrate (1:3:6) 
• 1383982-64-6 Dispiro[cyclohexane-1,2'-[2H]indene-1'(3'H),2''-[2H]iMidazol]-4''-aMine, 4-Methoxy-5''-Methyl-6'-[5-(1-propyn-1-yl)-3-pyridinyl]-, (1α,1'R,4β)- 
• 1383977-51-2 Tinospinoside C 
• 138-39-6 4-(AMINOMETHYL)BENZENESULFONAMIDE 
• 138395-78-5 2H-Cyclopentoxazol-2-one, hexahydro-4,5-dihydroxy-6-(hydroxymethyl)-, 3aR-(3a.alpha.,4.alpha.,5.beta.,6.alpha.,6a.alpha.)- 

Downstream Products

• 138402-11-6 Irbesartan 
• 138402-13-8 4-{[(benzyloxy)carbonyl]amino}tetrahydro-2H-pyran-4-carboxylic acid 
• 138402-22-9 1H-Indole-2-carboxylicacid,2-amino-2,3-dihydro-(9CI) 
• 138402-36-5 3-Pyridinemethanamine,5-chloro-(9CI) 
• 13840-33-0 LITHIUM HYPOCHLORITE 
• 13840-40-9 PHOSPHINEOXIDE 
• 138404-96-3 1,3-dihexadecanoylamino-2-valproyl-propan-ol 
• 138404-98-5 2-(decanoylamino)-1-[(decanoylamino)methyl]ethyl N-[(benzyloxy)carbonyl]glycinate 
• 138404-98-5 2-(decanoylamino)-1-[(decanoylamino)methyl]ethyl N-[(benzyloxy)carbonyl]glycinate 
• 138404-99-6 1,3-bis(hexadecanoylamino)propan-2-yl 2-phenylmethoxycarbonylaminoacet ate 
• 138405-00-2 2-[(3-phenylpropanoyl)amino]-1-{[(3-phenylpropanoyl)amino]methyl}ethyl N-[(benzyloxy)carbonyl]glycinate 
• 138405-01-3 1,3-bis(3-cyclohexylpropanoylamino)propan-2-yl 2-phenylmethoxycarbonyl aminoacetate 
• 138405-02-4 1,3-bis(adamantane-1-carbonylamino)propan-2-yl 2-phenylmethoxycarbonyl aminoacetate 
• 138405-07-9 1,2-Cyclopentanedimethanol,4-amino-,(1alpha,2beta,4alpha)-(9CI) 

Recommend Products

• 745814-08-8  2-(1-TRITYL-1H-TETRAZOL-5-YL)-4'-(1''-ETHOXYPENTANAMINYL)BIPHENYL 
• 1664-35-3  ethyl 1-aminocyclopentanecarboxylate 
• 177219-40-8  1-(pentanoylamino)cyclopentanecarboxamide 
• 124750-51-2  N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole 
• 138402-05-8  2-butyl-1,3-diaza-spiro[4.4]non-1-en-4one 
• 894806-38-3  2-n-butyl-3-[4-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)benzyl]-1,3-diazaspiro[4.4]non-1-ene-4-one 
• 143945-72-6  N-trityl-5-(2-bromophenyl)tetrazole 
• 894806-37-2  4-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]phenylboronic acid 
• 76-83-5  trityl chloride 
• 138401-24-8  4'-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-[1,1'-biphenyl]-2-carbonitrile 
• 1199814-94-2  2-(2-thienyl)-3-[2'-(1-trityl-1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-1,3-diazaspiro[4.4]non-1-en-4-one 
• 439904-79-7  N-pentanoyl-N-[[2'-[N-(triphenylmethyl)tetrazol-5-yl]-1,1'-biphenyl-4-yl]methyl]amine 
• 745814-11-3  C₁₃H₂₃NO₃ 
• 134603-82-0  1-(2'-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl)methanamine