224789-21-3

Basic information

• Product Name: 2-(2-ETHOXYPHENYL)-5-METHYL-7-PROPYL-3H-IMIDAZOL[5,1-F][1,2,4]-TRIAZIN-4-ONE
• Synonyms: 2-(2-ETHOXYPHENYL)-5-METHYL-7-PROPYL-3H-IMIDAZOL[5,1-F][1,2,4]-TRIAZIN-4-ONE;Imidazo[5,1-f][1,2,4]triazin-4(3H)-one,2-[2-ethoxylphenyl]-5-methyl-7;2-(2-Ethoxyphenyl)-5-methyl-7-propyl-imidazo[5,1-f][1,2,4]triazin-4(1H)-one;2-(2-ethoxyphenyl)-5-Methyl-7-propyliMidazo [5,1-f][1,2,4]triazin-4(3H)-one;IMidazo[5,1-f][1,2,4]triazin-4(1H)-one,2-(2-ethoxyphenyl)-5-Methyl-7-propyl-;Vardenafil Intermediate
• CAS NO: 224789-21-3
• Molecular Formula: C₁₇H₂₀N₄O₂
• Molecular Weight: 312.37
• EINECS: 1308068-626-2
• Product Categories: Heterocyclic Compounds;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 224789-21-3.mol

Chemical Properties

• Melting Point: 198-200°C
• Boiling Point: 519.699 °C at 760 mmHg
• Flash Point: 268.105 °C
• Appearance: Pale yellow solid
• Density: 1.266 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.632
• Storage Temp.: -20°C Freezer
• PKA: 10.08±0.20(Predicted)
• Water Solubility: 6.9mg/L at 20℃
• CAS DataBase Reference: 2-(2-ETHOXYPHENYL)-5-METHYL-7-PROPYL-3H-IMIDAZOL[5,1-F][1,2,4]-TRIAZIN-4-ONE(CAS DataBase Reference)
• NIST Chemistry Reference: 2-(2-ETHOXYPHENYL)-5-METHYL-7-PROPYL-3H-IMIDAZOL[5,1-F][1,2,4]-TRIAZIN-4-ONE(224789-21-3)
• EPA Substance Registry System: 2-(2-ETHOXYPHENYL)-5-METHYL-7-PROPYL-3H-IMIDAZOL[5,1-F][1,2,4]-TRIAZIN-4-ONE(224789-21-3)

Safety Data

• Hazardous Substances Data: 224789-21-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
2-(2-ETHOXYPHENYL)-5-METHYL-7-PROPYL-3H-IMIDAZOL[5,1-F][1,2,4]-TRIAZIN-4-ONE is used as a Vardenafil intermediate for the synthesis of Vardenafil (V098001), a medication that helps in treating erectile dysfunction. Its role in the pharmaceutical industry is significant as it contributes to the development and production of a drug that addresses a prevalent health issue.
Chemical Properties:
As a pale yellow solid, 2-(2-ETHOXYPHENYL)-5-METHYL-7-PROPYL-3H-IMIDAZOL[5,1-F][1,2,4]-TRIAZIN-4-ONE exhibits specific chemical properties that make it suitable for use as an intermediate in the synthesis of Vardenafil. Its physical appearance and chemical structure are essential factors in its application within the pharmaceutical industry.

Flammability and Explosibility

Nonflammable

InChI:InChI=1/C17H20N4O2/c1-4-8-14-18-11(3)15-17(22)19-16(20-21(14)15)12-9-6-7-10-13(12)23-5-2/h6-7,9-10H,4-5,8H2,1-3H3,(H,19,20,22)

Synthetic route

N-{1-[3-(2-ethoxyphenyl)-5-oxo-4,5-dihydro-[1,2,4]triazin-6-yl]ethyl}butyroamide (927690-90-2) → 2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (224789-21-3)

Conditions	Yield
With trichlorophosphate In toluene for 2h; Reflux;	78%
With trichlorophosphate
With trichlorophosphate In 1,2-dichloro-ethane for 2h; Reflux;
With trichlorophosphate In 1,2-dichloro-ethane for 2h; Reflux;

3-(2-ethoxy-benzoylamino)-5-methyl-2-propyl-3H-imidazole-4-carboxamide (865444-90-2) → 2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (224789-21-3)

Conditions	Yield
With potassium tert-butylate In tert-butyl alcohol at 160℃; for 30h;	72%
With potassium tert-butylate In tert-butyl alcohol at 160℃; for 30h; Sealed tube;	72%

5-methyl-2-propyl-3H-imidazole-4-carboxamide (865444-88-8) → 2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (224789-21-3)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: lithium hexamethyldisilazane / dimethylformamide; tetrahydrofuran / 0.17 h / -10 °C 1.2: 41 percent / Ph2P(O)ONH2 / tetrahydrofuran; dimethylformamide / 20 °C 2.1: 52 percent / pyridine / 2 h / 60 °C 3.1: 72 percent / KOtBu / 2-methyl-propan-2-ol / 30 h / 160 °C View Scheme

3-amino-5-methyl-2-propyl-3H-imidazole-4-carboxamide (865444-89-9) → 2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (224789-21-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 52 percent / pyridine / 2 h / 60 °C 2: 72 percent / KOtBu / 2-methyl-propan-2-ol / 30 h / 160 °C View Scheme

ethyl 5-methyl-2-propyl-3H-imidazole-4-carboxylate (146650-89-7) → 2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (224789-21-3)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: 53 percent / ammonium hydroxide / 24 h / 130 °C 2.1: lithium hexamethyldisilazane / dimethylformamide; tetrahydrofuran / 0.17 h / -10 °C 2.2: 41 percent / Ph2P(O)ONH2 / tetrahydrofuran; dimethylformamide / 20 °C 3.1: 52 percent / pyridine / 2 h / 60 °C 4.1: 72 percent / KOtBu / 2-methyl-propan-2-ol / 30 h / 160 °C View Scheme

2-butyrylaminopropionic acid (59875-04-6) → 2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (224789-21-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: Py; DMAP 2: POCl3 View Scheme
Multi-step reaction with 3 steps 1.1: dmap; pyridine / tetrahydrofuran / 4 h / Reflux 2.1: hydrazine hydrate / ethanol / 20 °C 2.2: 3.25 h / Reflux 3.1: trichlorophosphate / 1,2-dichloro-ethane / 2 h / Reflux View Scheme
Multi-step reaction with 3 steps 1: dmap; pyridine / tetrahydrofuran / 4 h / Reflux 2: ethanol / 3 h / Reflux 3: trichlorophosphate / 1,2-dichloro-ethane / 2 h / Reflux View Scheme

2-ethoxybenzonitrile (6609-57-0) → 2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (224789-21-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: AlMeClNH2 2: N2H4 3: POCl3 View Scheme
Multi-step reaction with 3 steps 1.1: trimethylaluminum; ammonium chloride / toluene / 7 h / 0 - 80 °C 2.1: hydrazine hydrate / ethanol / 20 °C 2.2: 3.25 h / Reflux 3.1: trichlorophosphate / 1,2-dichloro-ethane / 2 h / Reflux View Scheme
Multi-step reaction with 4 steps 1.1: amino(methyl)aluminum chloride / toluene / 6 h / 80 °C 2.1: hydrazine hydrate / ethanol / 20 °C 2.2: Reflux 3.1: ethanol / 3 h / Reflux 4.1: trichlorophosphate / 1,2-dichloro-ethane / 2 h / Reflux View Scheme

2-ethoxy-benzamidine hydrochloride (18637-00-8) → 2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (224789-21-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: N2H4 2: POCl3 View Scheme

ethyl 3-butyramido-2-oxobutyrate (68282-26-8) → 2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (224789-21-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: POCl3 View Scheme
Multi-step reaction with 2 steps 1.1: hydrazine hydrate / ethanol / 20 °C 1.2: 3.25 h / Reflux 2.1: trichlorophosphate / 1,2-dichloro-ethane / 2 h / Reflux View Scheme
Multi-step reaction with 2 steps 1: ethanol / 3 h / Reflux 2: trichlorophosphate / 1,2-dichloro-ethane / 2 h / Reflux View Scheme

2-ethoxybenzimidohydrazide (889943-46-8) → 2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (224789-21-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: POCl3 View Scheme
Multi-step reaction with 2 steps 1: ethanol / 3 h / Reflux 2: trichlorophosphate / 1,2-dichloro-ethane / 2 h / Reflux View Scheme

C9H13N3O*ClH + ethyl 3-butyramido-2-oxobutyrate (68282-26-8) → 2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (224789-21-3)

Conditions	Yield
Stage #1: C9H13N3O*ClH; ethyl 3-butyramido-2-oxobutyrate In ethanol at 70℃; for 4h; Stage #2: With trichlorophosphate In 1,2-dichloro-ethane for 2h; Heating / reflux;

2-butyrylaminopropionic acid (59875-04-6) + 2-ethoxy-benzamidine hydrochloride (18637-00-8) + Ethyl oxalyl chloride (4755-77-5) → 2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (224789-21-3)

Conditions	Yield
With pyridine; sodium hydrogencarbonate; hydrazine hydrate; trichlorophosphate In tetrahydrofuran; ethanol; ethyl acetate; 1,2-dichloro-ethane	4.00 g (28%)

3-(2-ethoxyphenyl)-6-ethyl-4H-[1,2,4]triazin-5-one (1417529-52-2) → 2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (224789-21-3)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) / tetrachloromethane / 14 h / Reflux; Inert atmosphere 2.1: ammonia / tetrahydrofuran / 20 °C 3.1: tertiary amine / dichloromethane / 0.08 h / Cooling 3.2: 1.17 h / 0 - 20 °C 4.1: trichlorophosphate / toluene / 2 h / Reflux View Scheme

6-(1-bromoethyl)-3-(2-ethoxyphenyl)-4H-[1,2,4]triazin-5-one (1417529-54-4) → 2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (224789-21-3)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: ammonia / tetrahydrofuran / 20 °C 2.1: tertiary amine / dichloromethane / 0.08 h / Cooling 2.2: 1.17 h / 0 - 20 °C 3.1: trichlorophosphate / toluene / 2 h / Reflux View Scheme

C13H16N4O2 (1417529-56-6) → 2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (224789-21-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: tertiary amine / dichloromethane / 0.08 h / Cooling 1.2: 1.17 h / 0 - 20 °C 2.1: trichlorophosphate / toluene / 2 h / Reflux View Scheme

2-Ethoxybenzamidine (53623-81-7) → 2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (224789-21-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: hydrazine hydrate / ethanol / 20 °C 1.2: 3.25 h / Reflux 2.1: trichlorophosphate / 1,2-dichloro-ethane / 2 h / Reflux View Scheme
Multi-step reaction with 3 steps 1.1: hydrazine hydrate / ethanol / 20 °C 1.2: Reflux 2.1: ethanol / 3 h / Reflux 3.1: trichlorophosphate / 1,2-dichloro-ethane / 2 h / Reflux View Scheme

2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (224789-21-3) → 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzenelsulfonic acid chloride (224789-26-8)

Conditions	Yield
With chlorosulfonic acid at 0 - 20℃;	91%
With chlorosulfonic acid for 12h; Cooling with ice;	76%
With chlorosulphuric acid for 12h; Cooling with ice;	76%

2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (224789-21-3) → 2-(2-ethoxy-5-iodo-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4(3H)-one

Conditions	Yield
With N-iodo-succinimide; trifluoroacetic acid at 0 - 20℃;	79%
With N-iodo-succinimide; trifluoroacetic acid at 0 - 20℃;	79%
With N-iodo-succinimide In trifluoroacetic acid at 0 - 20℃;	71%
With N-iodo-succinimide; trifluoroacetic acid at 0 - 20℃;

2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (224789-21-3) → 2-(2-ethoxy)-phenyl-5-methyl-7-n-propyl-3H-imidazolo[5,1-f][1,2,4]triazine-4-thione

Conditions	Yield
Stage #1: 2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one With pyridine; diphosphorus pentasulfide In toluene for 6h; Reflux; Stage #2: With ammonia; water In ethanol for 0.5h; Reflux;	72%
With pyridine; tetraphosphorus decasulfide for 6h; Reflux;	72%

4-ethylpiperazine (5308-25-8) + 2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (224789-21-3) → vardenafil (224785-90-4)

Conditions	Yield
Stage #1: 2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one With chlorosulfonic acid at 0 - 22℃; for 0.75h; Stage #2: 4-ethylpiperazine In dichloromethane at -3 - 25℃; for 0.75h; Product distribution / selectivity;

4-ethylpiperazine (5308-25-8) + citric acid (77-92-9) + 2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (224789-21-3) → vardenafil citrate (1193386-64-9)

Conditions	Yield
Stage #1: 2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one With chlorosulfonic acid at -5 - 20℃; Stage #2: 4-ethylpiperazine With sodium hydroxide In tetrahydrofuran; water at 15℃; pH=9 - 9.5; Stage #3: citric acid In tetrahydrofuran at 50 - 70℃;

2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (224789-21-3) → vardenafil (224785-90-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: chlorosulfonic acid / -5 - 20 °C 1.2: 15 °C / pH 9 - 9.5 1.3: 50 - 70 °C 2.1: sodium hydroxide / water / pH 9 - 10 View Scheme
Multi-step reaction with 2 steps 1: chlorosulfonic acid / 0 - 5 °C 2: dichloromethane / 25 - 30 °C View Scheme

2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (224789-21-3) → 2-[2-ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one hydrochloride

Conditions	Yield
Multi-step reaction with 3 steps 1.1: chlorosulfonic acid / -5 - 20 °C 1.2: 15 °C / pH 9 - 9.5 1.3: 50 - 70 °C 2.1: sodium hydroxide / water / pH 9 - 10 3.1: hydrogenchloride / water; acetone View Scheme
Multi-step reaction with 3 steps 1: chlorosulfonic acid / 0 - 5 °C 2: dichloromethane / 25 - 30 °C 3: hydrogenchloride; water / acetone View Scheme

2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (224789-21-3) → 2,2'-[(piperazine-1,4-disulfonyl)bis(2-ethoxy-5,1-phenylene)]-bis[5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(3H)-one] (1255919-03-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: chlorosulfonic acid / 0 - 5 °C 2: triethylamine / dichloromethane / 0.5 h / 25 - 30 °C View Scheme

2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (224789-21-3) → N-{[4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f]-1,2,4-triazin-2-yl) phenyl]sulfonyl}glycene (448184-54-1)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: chlorosulfonic acid / 0 - 5 °C 2.1: sodium hydroxide / water / 0.5 h / 25 - 30 °C 2.2: 2.5 h / 2 - 20 °C View Scheme

2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (224789-21-3) → C19H26N6O4S (448184-52-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: chlorosulfonic acid / 0 - 5 °C 2: dichloromethane / 1.33 h / 2 °C View Scheme

2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (224789-21-3) → {[2-({[4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f]-1,2,4-triazin-2-yl)phenyl]sulfonyl}amino)ethyl]amino}(oxo)acetic acid (448184-56-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: chlorosulfonic acid / 0 - 5 °C 2: dichloromethane / 1.33 h / 2 °C 3: triethylamine / 0.25 h / 25 - 30 °C 4: water; sodium hydroxide / methanol / 0.25 h / 25 °C View Scheme

2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (224789-21-3) → C23H30N6O7S

Conditions	Yield
Multi-step reaction with 3 steps 1: chlorosulfonic acid / 0 - 5 °C 2: dichloromethane / 1.33 h / 2 °C 3: triethylamine / 0.25 h / 25 - 30 °C View Scheme

2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (224789-21-3) → 2-{2-ethoxy-5-[(4-ethyl-4-hydroxy-4λ5-piperazin-1-yl)sulfonyl]phenyl}-5-methyl-7-propyl imidazo-[5,1-f]-1,2,4-triazin-4(3H)-one N-oxide (448184-48-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: chlorosulfonic acid / 0 - 5 °C 2: dichloromethane / 25 - 30 °C 3: peracetic acid / dichloromethane / 2 h / 0 - 5 °C View Scheme

2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (224789-21-3) → 2-{2-ethoxy-5-[(3-oxo-1-piperazinyl)sulfonyl]phenyl}-5-methyl-7-propylimidazo[5,1-f]-1,2,4-triazin-4(3H)-one (448184-58-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: chlorosulfonic acid / 0 - 5 °C 2: dichloromethane / 0.5 h / 25 - 30 °C View Scheme

2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (224789-21-3) → vardenafil hydrochloride

Conditions	Yield
Multi-step reaction with 3 steps 1: chlorosulfonic acid / dichloromethane / 24 h / 23 - 90 °C 2: dichloromethane 3: hydrogenchloride / water; acetone / 50 °C View Scheme

Upstream product

• 68282-26-8 ethyl 3-butyramido-2-oxobutyrate 
• 59875-04-6 2-butyrylaminopropionic acid 
• 18637-00-8 2-ethoxy-benzamidine hydrochloride 
• 4755-77-5 Ethyl oxalyl chloride 
• 927690-90-2 N-{1-[3-(2-ethoxyphenyl)-5-oxo-4,5-dihydro-[1,2,4]triazin-6-yl]ethyl}butyroamide 
• 6609-57-0 2-ethoxybenzonitrile 
• 53623-81-7 2-Ethoxybenzamidine 
• 1417529-56-6 C₁₃H₁₆N₄O₂ 
• 1417529-54-4 6-(1-bromoethyl)-3-(2-ethoxyphenyl)-4H-[1,2,4]triazin-5-one 
• 1417529-52-2 3-(2-ethoxyphenyl)-6-ethyl-4H-[1,2,4]triazin-5-one 
• 889943-46-8 2-ethoxybenzimidohydrazide 
• 146650-89-7 ethyl 5-methyl-2-propyl-3H-imidazole-4-carboxylate 
• 865444-89-9 3-amino-5-methyl-2-propyl-3H-imidazole-4-carboxamide 
• 865444-88-8 5-methyl-2-propyl-3H-imidazole-4-carboxamide 

Downstream Products

• 224785-90-4 vardenafil 
• 1193386-64-9 vardenafil citrate 
• 224785-90-4 vardenafil 

Relevant articles and documents

A novel method for the synthesis of imidazo[5,1-f][1,2,4]triazin-4(3H)-ones

Imidazo[5,1-f][1,2,4]triazinones, as isosteres of purine, are of interest for pharmaceutical research. The syntheses reported in the literature generally require several steps. We report a novel method to access a broad range of diversely substituted derivatives. The key step is the electrophilic N-amination of 3H-imidazoles containing a 4-carbonyl group. Several different substituted imidazoles have been N-aminated in this manner. The resulting N-aminoimidazoles were cyclized under different conditions to the corresponding imidazotriazinones, which allowed for additional diversification. This novel method was applied in a formal synthesis of vardenafil, a well-known representative of this class of compounds. Furthermore, we report the first synthesis of a 7-aryl-imidazotriazinone via bromination of an unsubstituted imidazotriazinone followed by a Suzuki coupling.

NOVEL COMPOUNDS FOR USE IN COGNITION IMPROVEMENT

Novel compounds for use in cognition improvement It relates to certain compounds having a polycyclic structure and a -(C=O)NRaRb moiety, wherein the polycyclic structure comprises at least three ring systems, wherein one ring system is a polycyclic ring system comprising from 2 to 4 rings; at least one ring is an aromatic ring; and wherein the structure comprises at least 3 nitrogen atoms and 1 oxygen atom. It also relates to pharmaceutical compositions containing them, and to their use in medicine, in particular in the treatment and/or prevention of neurological disorders coursing with a cognition deficit or impairment, or neurodegenerative diseases.

NOVEL COMPOUNDS AS DUAL INHIBITORS OF PHOSPHODIESTERASES AND HISTONE DEACETYLASES

It relates to certain compounds having a polycyclic structure and a hydroxamic acid moiety, wherein the polycyclic structure comprises at least three ring systems, wherein one ring system is a polycyclic ring system comprising from 2 to 4 rings; at least one ring is an aromatic ring; and wherein the structure comprises at least 3 nitrogen atoms and 1 oxygen atom. It also relates to a process for their preparation, as well as to pharmaceutical compositions containing them, and to their use in medicine, in particular in the treatment and/or prevention of neurological disorders coursing with a cognition deficit or impairment, or neurodegenerative diseases. wherein B1 is a radical selected from the group consisting of formula (A"), formula (B"), formula (C"), and formula (D"):

Alternative method for the synthesis of imidazo[5,1-f][1,2,4]triazin-4(3H)- one - A substrate for the preparation of phosphodiesterase (5) inhibitors

Imidazo[5,1-f][1,2,4]triazin-4(3H)-ones, as isosteres of purine, are of interest for pharmaceutical research as potential substrates for the synthesis of cGMP-PDE5 inhibitors. We present a novel, alternative method for the synthesis of imidazotriazinones, that differs from the previously reported ones with respect to the method of construction of the triazinone ring in the molecule. The key step in our approach is condensation of an appropriate α-keto-ester with amidrazones, leading to the triazinone heterocycle. Several different substituted imidazolotriazinones have been synthesized in this manner.

NEW AGENTS FOR THE TREATMENT OF THE LOW URINARY TRACT DYSFUNCTIONS

The present invention relates to novel compounds that are derivatives of 5 -phosphodiesterase inhibitors that comprise in their formula a polysulfurated group and that are useful for treating dysfunctions of low urinary tract such as incontinence, benign prostatic hyperplasia and erectile dysfunction.

Methods for synthesizing imidazotriazinones

Methods of synthesizing imidazotriazinones, such as vardenafil, and compositions useful for the same are disclosed.

2-phenyl substituted imidazotriazinones as phosphodiesterase inhibitors

The 2-phenyl-substituted imidazotriazinones having short, unbranched alkyl radicals in the 9-position are prepared from the corresponding 2-phenyl-imidazotriazinones by chlorosulphonation and subsequent reaction with the amines. The compounds inhibit cGMP-metabolizing phosphodiesterases and are suitable for use as active compounds in pharmaceuticals, for the treatment of cardiovascular and cerebrovascular disorders and/or disorders of the urogenital system, in particular for the treatment of erectile dysfunction.

2-Phenyl-substituited Imidazotriazinones as Phoshodiesterase Inhibitors

2-(Sulfamoyl-substituted phenyl)-3H-imidazo (5,1-f) (1,2,4) triazin-4-ones (I) are new. Imidazotriazinones of formula (I) and their salts, N-oxides and isomeric forms are new: R1 = H or 1-4C alkyl; R2 = 1-4C straight chain alkyl; R3, R4 = H, 2-8C alkenyl, 1-8C alkoxy or 1-10C alkyl (optionally interrupted by O and/or substituted by a very wide range of specific groups); or R3 or R4 = NR20R21, adamantyl, 2,2-dimethyl-4-phenyl-1,3-dioxan-5-yl, sulfolanyl, hydroxy-sulfolanyl, 2-oxo-tetrahydrofuran-3-yl; or 3-8C cycloalkyl, 6-10C aryl or 5-7 membered heterocycle, all optionally substituted by specific groups; or NR3R4 = (a) optionally benzo-fused, saturated, partially unsaturated or unsaturated 5-7 membered heterocycle, optionally containing 1-3 of S, N, O and NR37 and optionally substituted by a very wide range of specific groups; or (b) a group of formula (i)-(iv); R20,R21 = H or 1-6C alkyl; R37 = H, OH, CHO, CF3, up to 4C acyl, up to 4C alkoxycarbonyl, 1-4C alkoxy, 1-6C alkyl (optionally substituted by specific groups) or -(CO)iE; i = 0 or 1; E = 3-7C cycloalkyl or benzyl; 6-10C aryl or 5- or 6-membered heteroaryl, both optionally substituted by specific groups ; or 5-methyl-1-oxo-2,1,3-oxadiazol-4-yl, N-methylpiperazino or morpholino; R5,R6 = H, 1-6C alkyl, OH or 1-6C alkoxy. The full definitions are given in the DEFINITIONS (Full Definitions) field. An Independent claim is included for the preparation of (I).

Imidazo[5,1-f][1,2,4]triazin-4(3H)-ones, a new class of potent PDE 5 inhibitors

2-Aryl-substituted imidazo[5,1-f][1,2,4]triazin-4(3H)-ones represent a new class of potent cGMP-PDE 5 inhibitors that prove to be superior to other purine-isosteric inhibitors. Subnanomolar inhibitors of PDE 5 with activity in in vivo models for erectile dysfunction have been identified. BAY 38-9456 (Vardenafil-hydrochloride) has been selected for clinical studies in the indication of erectile dysfunction.