Avanafil supplier | CasNO.330784-47-9

Name
Avanafil
EINECS
CAS No. 330784-47-9
Article Data20
CAS DataBase
Density 1.373 g/cm³
Solubility
Melting Point 150-152 °C
Formula C₂₃H₂₆ClN₇O₃
Boiling Point
Molecular Weight 483.958
Flash Point
Transport Information
Appearance White solid
Safety
Risk Codes
Molecular Structure
Hazard Symbols
Synonyms (S)-2-(2-Hydroxymethyl-1-pyrrolidinyl)-4-(3-chloro-4-methoxybenzylamino)-5-[(2-pyrimidinylmethyl)carbamoyl]pyrimidine;TA 1790;
PSA 125.39000
LogP 2.96070

Synthetic route

: 330785-84-7
4-{[(3-chloro-4-methoxyphenyl)methyl]amino}-2-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]pyrimidine-5-carboxylic acid

: 75985-45-4
2-aminomethylpyrimidine

: 330784-47-9
avanafil

Conditions

Conditions	Yield
With dicyclohexyl-carbodiimide; 1-hydroxy-1,2,3-benzotriazine-4(3H)-one In N,N-dimethyl-formamide at 0℃; Temperature;	99%
With 5, 10, 15, 20-tetrakis[4-(dihydroxyboryl)phenyl]-21H,23H-porphine In toluene for 16h; Time; Reflux; Green chemistry;	91.2%
With benzotriazol-1-ol; dicyclohexyl-carbodiimide In dimethyl sulfoxide at 20℃; for 4h;	90%
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In DMF (N,N-dimethyl-formamide) at 20℃; for 8h;

: 2-chloro-4-((3-chloro-4-methoxybenzyl)amino)-N-[pyrimidin-2ylmethyl]pyrimidine-5-carboxamide

: 23356-96-9
(S)-1-Pyrrolidin-2-yl-methanol

: 330784-47-9
avanafil

Conditions

Conditions	Yield
With triethylamine In tetrahydrofuran at 20℃; for 20h;	97.2%

: 4-((3-chloro-4-methoxybenzyl)amino)-2-(methylthio)-N-(pyrimidin-2-ylmethyl)pyrimidine-5-formamide

: 23356-96-9
(S)-1-Pyrrolidin-2-yl-methanol

: 330784-47-9
avanafil

Conditions

Conditions	Yield
With 1H-imidazole In toluene at 20℃; for 18h; Solvent; Reagent/catalyst;	97%
With triethylamine at 20 - 30℃; for 1h; Solvent;	1.1 g

: 4-[(3-chloro-4-methoxybenzyl)amino]-2-methanesulfonyl-N-(2-pyrimidinylmethyl)-5-pyrimidinecarboxamide

: 23356-96-9
(S)-1-Pyrrolidin-2-yl-methanol

: 330784-47-9
avanafil

Conditions

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In chloroform at 50℃; Temperature;	90.5%
With N-ethyl-N,N-diisopropylamine In isopropyl alcohol at 20℃; for 5h;	87.5%
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; Temperature; Green chemistry;	87%

: ethyl (S)-4-((3-chloro-4-methoxybenzyl)amino)-2-(2-(hydroxymethyl)tetrahydropyrrole-1-yl)-5-pyrimidinecarboxylate

: 75985-45-4
2-aminomethylpyrimidine

: 330784-47-9
avanafil

Conditions

Conditions	Yield
Stage #1: ethyl (S)-4-((3-chloro-4-methoxybenzyl)amino)-2-(2-(hydroxymethyl)tetrahydropyrrole-1-yl)-5-pyrimidinecarboxylate With dimethyl sulfoxide; citric acid; sodium hydroxide In water for 15h; Stage #2: 2-aminomethylpyrimidine With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide for 8h;	87%
In dichloromethane at 20℃;	44%

: 6-(3-chloro-4-methoxy-benzylamino)-1,2-dihydropyrimidin-2-one-5-(N-2-methylpyrimidinyl)formamide

: 23356-96-9
(S)-1-Pyrrolidin-2-yl-methanol

: 330784-47-9
avanafil

Conditions

Conditions	Yield
Stage #1: 6-(3-chloro-4-methoxy-benzylamino)-1,2-dihydropyrimidin-2-one-5-(N-2-methylpyrimidinyl)formamide With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 20 - 60℃; for 24h; Inert atmosphere; Stage #2: (S)-1-Pyrrolidin-2-yl-methanol With sodium hydride In tetrahydrofuran at 65℃; for 5h;	81.3%

: 4-[(3-chloro-4-methoxybenzyl)amino]-2-[2-(hydroxymethyl)-1-pyrrolidinyl]pyrimidine

: N-(2-methylpyrimidine)methanamide

: 330784-47-9
avanafil

Conditions

Conditions	Yield
Stage #1: 4-[(3-chloro-4-methoxybenzyl)amino]-2-[2-(hydroxymethyl)-1-pyrrolidinyl]pyrimidine With bromine; sodium hydroxide for 0.0833333h; Microwave irradiation; Stage #2: N-(2-methylpyrimidine)methanamide With tris(2,4-di-t-butyl)phenoxy phosphazene; sodium methylate; nickel diacetate In 1,2-dimethoxyethane at 120℃; for 10h; Inert atmosphere;	81.1%

: 330785-84-7
4-{[(3-chloro-4-methoxyphenyl)methyl]amino}-2-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]pyrimidine-5-carboxylic acid

: 2-aminomethylpyrimidine methanesulfonate

: 330784-47-9
avanafil

Conditions

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 15 - 25℃;	67%

: 1246834-64-9
2-aminomethylpyrimidine acetate

: 23356-96-9
(S)-1-Pyrrolidin-2-yl-methanol

: 41965-95-1
(3-chloro-4-methoxyphenyl)methylamine hydrogen chloride

: 2972-52-3
2,4-dichloropyrimidine-5-carbonyl chloride

: 330784-47-9
avanafil

Conditions

Conditions	Yield
Stage #1: 2-aminomethylpyrimidine acetate; 2,4-dichloropyrimidine-5-carbonyl chloride With triethylamine In dichloromethane for 1h; Cooling with ice; Stage #2: (3-chloro-4-methoxyphenyl)methylamine hydrogen chloride With triethylamine In dichloromethane for 2h; Stage #3: (S)-1-Pyrrolidin-2-yl-methanol In dichloromethane at 20℃;	64%

...Expand

: 4-(3-chloro-4-methoxybenzylamino)-2-[(S)-2-hydroxymethylpyrrolidinyl-1-yl]-5-pyrimidinecarboxylic acid chloride

: 75985-45-4
2-aminomethylpyrimidine

: 330784-47-9
avanafil

Conditions

Conditions	Yield
With triethylamine In dichloromethane at 20℃;	64%

: 2-chloro-4-((3-chloro-4-methoxybenzyl)amino)-N-[pyrimidin-2ylmethyl]pyrimidine-5-carboxamide

: 330784-47-9
avanafil

Conditions

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 100℃; Reagent/catalyst; Solvent; Temperature;	61%

: 330785-84-7
4-{[(3-chloro-4-methoxyphenyl)methyl]amino}-2-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]pyrimidine-5-carboxylic acid

: 1246834-64-9
2-aminomethylpyrimidine acetate

: 330784-47-9
avanafil

Conditions

Conditions	Yield
Stage #1: 2-aminomethylpyrimidine acetate With triethylamine In N,N-dimethyl-formamide for 0.5h; Stage #2: 4-{[(3-chloro-4-methoxyphenyl)methyl]amino}-2-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]pyrimidine-5-carboxylic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 8h;	60%

: 2,4-dichloro-N-(pyrimidin-2-ylmethyl)-5-pyrimidinecarboxamide

: 23356-96-9
(S)-1-Pyrrolidin-2-yl-methanol

: 41965-95-1
(3-chloro-4-methoxyphenyl)methylamine hydrogen chloride

: 330784-47-9
avanafil

Conditions

Conditions	Yield
Stage #1: 2,4-dichloro-N-(pyrimidin-2-ylmethyl)-5-pyrimidinecarboxamide; (3-chloro-4-methoxyphenyl)methylamine hydrogen chloride With triethylamine for 2h; Stage #2: (S)-1-Pyrrolidin-2-yl-methanol at 20℃; for 4h;	32%

...Expand

: 330785-84-7
4-{[(3-chloro-4-methoxyphenyl)methyl]amino}-2-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]pyrimidine-5-carboxylic acid

: 2-aminomethylpyrimidine acetic acid

: 330784-47-9
avanafil

Conditions

Conditions	Yield
Stage #1: 4-{[(3-chloro-4-methoxyphenyl)methyl]amino}-2-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]pyrimidine-5-carboxylic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 25 - 35℃; for 0.333333h; Stage #2: 2-aminomethylpyrimidine acetic acid With triethylamine In N,N-dimethyl-formamide at 25 - 35℃; for 9h; Stage #3: In methanol at 25 - 35℃; for 0.75h;	68 g

Yield

Stage #1: 4-{[(3-chloro-4-methoxyphenyl)methyl]amino}-2-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]pyrimidine-5-carboxylic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 25 - 35℃; for 0.333333h;
Stage #2: 2-aminomethylpyrimidine acetic acid With triethylamine In N,N-dimethyl-formamide at 25 - 35℃; for 9h;
Stage #3: In methanol at 25 - 35℃; for 0.75h;

68 g

: 330786-34-0
4-[(3-chloro-4-methoxybenzyl)amino]-2-(methylsulfanyl)pyrimidine-5-carboxylic acid

: 330784-47-9
avanafil

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C 2: 3-chloro-benzenecarboperoxoic acid / 0 °C 3: 20 - 120 °C View Scheme
Multi-step reaction with 3 steps 1.1: thionyl chloride / toluene; N,N-dimethyl-formamide / 2.5 h / Reflux 1.2: 15 - 30 °C 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1 h / 25 - 30 °C 3.1: triethylamine / dichloromethane View Scheme
Multi-step reaction with 4 steps 1.1: thionyl chloride / toluene; N,N-dimethyl-formamide / 2.5 h / Reflux 1.2: 15 - 30 °C 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1 h / 25 - 30 °C 3.1: triethylamine / dichloromethane 4.1: sulfuric acid / ethanol / Reflux 4.2: 5 h View Scheme

: 4-((3-chloro-4-methoxybenzyl)amino)-2-(methylthio)-N-(pyrimidin-2-ylmethyl)pyrimidine-5-formamide

: 330784-47-9
avanafil

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1: 3-chloro-benzenecarboperoxoic acid / 0 °C 2: 20 - 120 °C View Scheme
Multi-step reaction with 2 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1 h / 25 - 30 °C 2: triethylamine / dichloromethane View Scheme
Multi-step reaction with 3 steps 1.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1 h / 25 - 30 °C 2.1: triethylamine / dichloromethane 3.1: sulfuric acid / ethanol / Reflux 3.2: 5 h View Scheme
Multi-step reaction with 4 steps 1.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1 h / 25 - 30 °C 2.1: triethylamine / dichloromethane 3.1: thionyl chloride / toluene; N,N-dimethyl-formamide / 2.5 h / Reflux 4.1: sodium tetrahydroborate / tetrahydrofuran / 0 - 5 °C 4.2: 60 - 70 °C View Scheme

: 5909-24-0
4-chloro-2-methanesulfanylpyrimidine-5-carboxylic acid ethyl ester

: 330784-47-9
avanafil

Conditions

Conditions	Yield
Multi-step reaction with 5 steps 1: triethylamine / tetrahydrofuran / 20 °C 2: sodium hydroxide / water; ethanol / 20 °C 3: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C 4: 3-chloro-benzenecarboperoxoic acid / 0 °C 5: 20 - 120 °C View Scheme
Multi-step reaction with 5 steps 1: sodium carbonate / water / 4 h / 25 - 30 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1 h / 0 - 5 °C 3: triethylamine / dichloromethane / 5 - 10 °C 4: sodium hydroxide / water / 8.17 h / 25 - 100 °C 5: triethylamine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 14 h / 0 - 5 °C View Scheme
Multi-step reaction with 5 steps 1: sodium carbonate; tetrabutylammomium bromide / water / 8 h / 25 - 30 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1 h / 0 - 5 °C 3: triethylamine / dichloromethane / 5 - 10 °C 4: sodium hydroxide / water / 8.17 h / 25 - 100 °C 5: triethylamine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 14 h / 0 - 5 °C View Scheme

: 330785-81-4
ethyl 4-[(3-chloro-4-methoxybenzyl)amino]-2-(methylsulfanyl)pyrimidine-5-carboxylate

: 330784-47-9
avanafil

Conditions

Conditions	Yield
Multi-step reaction with 4 steps 1: sodium hydroxide / water; ethanol / 20 °C 2: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C 3: 3-chloro-benzenecarboperoxoic acid / 0 °C 4: 20 - 120 °C View Scheme
Multi-step reaction with 4 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1 h / 0 - 5 °C 2: triethylamine / dichloromethane / 5 - 10 °C 3: sodium hydroxide / water / 8.17 h / 25 - 100 °C 4: triethylamine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 14 h / 0 - 5 °C View Scheme
Multi-step reaction with 4 steps 1.1: water; sodium hydroxide / methanol / Reflux 2.1: thionyl chloride / toluene; N,N-dimethyl-formamide / 2.5 h / Reflux 2.2: 15 - 30 °C 3.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1 h / 25 - 30 °C 4.1: triethylamine / dichloromethane View Scheme

: 115514-77-7
(3-chloro-4-methoxyphenyl)methanamine

: 330784-47-9
avanafil

Conditions

Conditions	Yield
Multi-step reaction with 5 steps 1: triethylamine / tetrahydrofuran / 20 °C 2: sodium hydroxide / water; ethanol / 20 °C 3: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 20 °C 4: 3-chloro-benzenecarboperoxoic acid / 0 °C 5: 20 - 120 °C View Scheme
Multi-step reaction with 6 steps 1: methanol / 0.25 h / 60 - 65 °C 2: sodium carbonate; tetrabutylammomium bromide / water / 8 h / 25 - 30 °C 3: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1 h / 0 - 5 °C 4: triethylamine / dichloromethane / 5 - 10 °C 5: sodium hydroxide / water / 8.17 h / 25 - 100 °C 6: triethylamine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 14 h / 0 - 5 °C View Scheme
Multi-step reaction with 5 steps 1.1: tetrabutylammomium bromide; sodium carbonate / dichloromethane; water / 25 - 30 °C 2.1: water; sodium hydroxide / methanol / Reflux 3.1: thionyl chloride / toluene; N,N-dimethyl-formamide / 2.5 h / Reflux 3.2: 15 - 30 °C 4.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1 h / 25 - 30 °C 5.1: triethylamine / dichloromethane View Scheme

: 53554-29-3
ethyl 4-hydroxy-2-(methylthio)pyrimidine-5-carboxylate

: 330784-47-9
avanafil

Conditions

Conditions	Yield
Multi-step reaction with 6 steps 1: trichlorophosphate / toluene / 4 h / 55 - 105 °C 2: sodium carbonate; tetrabutylammomium bromide / water / 8 h / 25 - 30 °C 3: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1 h / 0 - 5 °C 4: triethylamine / dichloromethane / 5 - 10 °C 5: sodium hydroxide / water / 8.17 h / 25 - 100 °C 6: triethylamine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 14 h / 0 - 5 °C View Scheme
Multi-step reaction with 6 steps 1: trichlorophosphate / toluene / 4 h / 55 - 105 °C 2: sodium carbonate / water / 4 h / 25 - 30 °C 3: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1 h / 0 - 5 °C 4: triethylamine / dichloromethane / 5 - 10 °C 5: sodium hydroxide / water / 8.17 h / 25 - 100 °C 6: triethylamine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 14 h / 0 - 5 °C View Scheme
Multi-step reaction with 6 steps 1: trichlorophosphate / acetonitrile / 6 h / Reflux 2: triethylamine / acetone / 3 h / 20 °C 3: methanol; sodium hydroxide / 4.5 h / 20 - 30 °C 4: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol; triethylamine / N,N-dimethyl-formamide; N,N-dimethyl-aniline / 7 h / 60 °C 5: acetic acid; dihydrogen peroxide / 4 h / 65 - 80 °C 6: N-ethyl-N,N-diisopropylamine / isopropyl alcohol / 5 h / 20 °C View Scheme

: 330785-82-5
4-(3-chloro-4-methoxybenzylamino)-5-ethoxycarbonyl-2-methylsulfinylpyrimidine

: 330784-47-9
avanafil

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 5 - 10 °C 2: sodium hydroxide / water / 8.17 h / 25 - 100 °C 3: triethylamine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 14 h / 0 - 5 °C View Scheme
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / -5 - 30 °C / Large scale 2: sodium hydroxide / dimethyl sulfoxide; water / 25 - 35 °C / Large scale 3: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 15 - 25 °C View Scheme

: ethyl (S)-4-((3-chloro-4-methoxybenzyl)amino)-2-(2-(hydroxymethyl)tetrahydropyrrole-1-yl)-5-pyrimidinecarboxylate

: 330784-47-9
avanafil

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide / water / 8.17 h / 25 - 100 °C 2: triethylamine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 14 h / 0 - 5 °C View Scheme
Multi-step reaction with 2 steps 1.1: sodium hydroxide / water; dimethyl sulfoxide / 20 °C / Cooling with ice 2.1: triethylamine / N,N-dimethyl-formamide / 0.5 h 2.2: 8 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: sodium hydroxide / water; dimethyl sulfoxide / 20 °C / Cooling with ice 2: thionyl chloride / 4 h / 80 °C 3: triethylamine / dichloromethane / 20 °C View Scheme

: 372118-67-7
1-(pyrimidin-2-yl)methanamine hydrochloride

: 330785-84-7
4-{[(3-chloro-4-methoxyphenyl)methyl]amino}-2-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]pyrimidine-5-carboxylic acid

: 330784-47-9
avanafil

Conditions

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In N,N-dimethyl-formamide at 0 - 5℃; for 14h; Time;	145 g

: (3-chloro-4-methoxyphenyl)methanamine malate

: 330784-47-9
avanafil

Conditions

Conditions	Yield
Multi-step reaction with 5 steps 1: sodium carbonate; tetrabutylammomium bromide / water / 8 h / 25 - 30 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1 h / 0 - 5 °C 3: triethylamine / dichloromethane / 5 - 10 °C 4: sodium hydroxide / water / 8.17 h / 25 - 100 °C 5: triethylamine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 14 h / 0 - 5 °C View Scheme

Yield

Multi-step reaction with 5 steps
1: sodium carbonate; tetrabutylammomium bromide / water / 8 h / 25 - 30 °C
2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1 h / 0 - 5 °C
3: triethylamine / dichloromethane / 5 - 10 °C
4: sodium hydroxide / water / 8.17 h / 25 - 100 °C
5: triethylamine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 14 h / 0 - 5 °C
View Scheme

: 4-[(3-chloro-4-methoxybenzyl)amino]-2-(methyl sulfinyl)-N-(pyrimidin-2-ylmethyl)pyrimidine-5-carboxamide

: 330784-47-9
avanafil

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1.1: triethylamine / dichloromethane 2.1: sulfuric acid / ethanol / Reflux 2.2: 5 h View Scheme
Multi-step reaction with 3 steps 1.1: triethylamine / dichloromethane 2.1: thionyl chloride / toluene; N,N-dimethyl-formamide / 2.5 h / Reflux 3.1: sodium tetrahydroborate / tetrahydrofuran / 0 - 5 °C 3.2: 60 - 70 °C View Scheme

: 4-[(3-chloro-4-methoxybenzyl)amino]-2-(methyl sulfinyl)-N-(pyrimidin-2-ylmethyl)pyrimidine-5-carboxamide

: 23356-96-9
(S)-1-Pyrrolidin-2-yl-methanol

: 330784-47-9
avanafil

Conditions

Conditions	Yield
With triethylamine In dichloromethane	8 g

: C23H24ClN7O4

: 330784-47-9
avanafil

Conditions

Conditions	Yield
Stage #1: C23H24ClN7O4 With sulfuric acid In ethanol Reflux; Stage #2: With sodium tetrahydroborate; lithium bromide In ethanol for 5h;	7.5 g

: C23H23Cl2N7O3

: 330784-47-9
avanafil

Conditions

Conditions	Yield
Stage #1: C23H23Cl2N7O3 With sodium tetrahydroborate In tetrahydrofuran at 0 - 5℃; Stage #2: With potassium hydroxide In water at 60 - 70℃;	40 g

: 320407-92-9
4-(bromomethyl)-2-chloro-1-methoxybenzene

: 330784-47-9
avanafil

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1.1: potassium iodide; triethylamine / ethanol / 3 h / 50 - 80 °C 2.1: 1,8-diazabicyclo[5.4.0]undec-7-ene; (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate / acetonitrile / 24 h / 20 - 60 °C / Inert atmosphere 2.2: 5 h / 55 °C 3.1: bromine; sodium hydroxide / 0.08 h / Microwave irradiation 3.2: 10 h / 120 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1.1: potassium iodide; triethylamine / ethanol / 3 h / 50 - 80 °C 2.1: sodium hydroxide; iodine / 0.08 h / Microwave irradiation 2.2: 10 h / 110 °C / Inert atmosphere 3.1: 1,8-diazabicyclo[5.4.0]undec-7-ene; (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate / acetonitrile / 24 h / 20 - 60 °C / Inert atmosphere 3.2: 5 h / 65 °C View Scheme

Yield

Multi-step reaction with 3 steps
1.1: potassium iodide; triethylamine / ethanol / 3 h / 50 - 80 °C
2.1: 1,8-diazabicyclo[5.4.0]undec-7-ene; (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate / acetonitrile / 24 h / 20 - 60 °C / Inert atmosphere
2.2: 5 h / 55 °C
3.1: bromine; sodium hydroxide / 0.08 h / Microwave irradiation
3.2: 10 h / 120 °C / Inert atmosphere
View Scheme

Multi-step reaction with 3 steps
1.1: potassium iodide; triethylamine / ethanol / 3 h / 50 - 80 °C
2.1: sodium hydroxide; iodine / 0.08 h / Microwave irradiation
2.2: 10 h / 110 °C / Inert atmosphere
3.1: 1,8-diazabicyclo[5.4.0]undec-7-ene; (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate / acetonitrile / 24 h / 20 - 60 °C / Inert atmosphere
3.2: 5 h / 65 °C
View Scheme

: 330784-47-9
avanafil

: 77-92-9
citric acid

: avanafil-citric acid

Conditions

Conditions	Yield
In acetone at 25℃; for 8h; Solvent; Sealed tube;	96.5%

: 330784-47-9
avanafil

: 4-nitrophenyl 3-[(25)-2,3-bis(nitrooxy)propoxy] propanoate

: [(2S)-1-(4-{[(3-chloro-4-methoxyphenyl)methyl]amino}-5-{[(pyrimidin-2-yl)methyl]carbamoyl}pyrimidin-2-yl)pyrrolidin-2-yl]methyl 3-[(2S)-2,3-bis(nitrooxy)propoxy]propanoate

Conditions

Conditions	Yield
With dmap In dichloromethane at 20℃;	95%

: 330784-47-9
avanafil

: 1178531-55-9
(5S)-5,6-bis(nitrooxy)hexanoic acid

: [(2S)-1-(4-{[(3-chloro-4-methoxyphenyl)methyl]amino}-5-{[(pyrimidin-2-yl)methyl]carbamoyl}pyrimidin-2-yl)pyrrolidin-2-yl]methyl (5S)-5,6-bis(nitrooxy)hexanoate

Conditions

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃;	94.5%

: 330784-47-9
avanafil

: 74754-55-5
6-(nitrooxy)hexanoic acid

: (S)-(1-(4-(3-chloro-4-methoxybenzylamino)-5-(pyrimidin-2-ylmethylcarbamoyl)pyrimidin-2-yl)pyrrolidin-2-yl)methyl 6-(nitrooxy)hexanoate

Conditions

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃;	93%

: 330784-47-9
avanafil

: 1321458-84-7
2-(2-(nitrooxy)ethoxy)acetic acid

: (S)-(1-(4-(3-chloro-4-methoxybenzylamino)-5-(pyrimidin-2-ylmethylcarbamoyl)pyrimidin-2-yl)pyrrolidin-2-yl)methyl 2-(2-(nitrooxy)ethoxy)acetate

Conditions

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃;	52%

: 330784-47-9
avanafil

: 19961-29-6
boron monobromide

: 144-55-8
sodium hydrogencarbonate

: 330785-05-2
(S)-2-(2-hydroxymethyl-1-pyrrolidinyl)-4-(3-chloro-4-hydroxybenzylamino)-5-[N-(2-pyrimidylmethyl)carbamoyl]pyrimidine

Conditions

Conditions	Yield
In tetrahydrofuran; methanol; dichloromethane; chloroform; ethyl acetate

...Expand

Avanafil Specification

The Avanafil with the CAS number 330784-47-9 is also called 5-Pyrimidinecarboxamide,4-[[(3-chloro-4-methoxyphenyl)methyl]amino]-2-[(2S)-2-(hydroxymethyl)-1-pyrrolidinyl]-N-(2-pyrimidinylmethyl)-. The IUPAC name is 4-[(3-chloro-4-methoxyphenyl)methylamino]-2-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-N-(pyrimidin-2-ylmethyl)pyrimidine-5-carboxamide. Its molecular formula is C₂₃H₂₆ClN₇O₃. The classification code is Treatment of erectile dysfunction.

The properties of the Avanafil are: (1)ACD/LogP: 1.84; (2)# of Rule of 5 Violations: 1; (3)ACD/LogD (pH 5.5): 0; (4)ACD/LogD (pH 7.4): 1; (5)ACD/BCF (pH 5.5): 1; (6)ACD/BCF (pH 7.4): 6; (7)ACD/KOC (pH 5.5): 9; (8)ACD/KOC (pH 7.4): 124; (9)#H bond acceptors: 10; (10)#H bond donors: 3; (11)#Freely Rotating Bonds: 9; (12)Polar Surface Area: 125.39 Å²; (13)Index of Refraction: 1.651; (14)Molar Refractivity: 128.832 cm³; (15)Molar Volume: 352.588 cm³; (16)Polarizability: 51.073×10^-24cm³; (17)Surface Tension: 69.965 dyne/cm.

You can still convert the following datas into molecular structure:
(1)SMILES: Clc1c(OC)ccc(c1)CNc3nc(ncc3C(=O)NCc2ncccn2)N4[C@@H](CCC4)CO
(2)InChI: InChI=1/C23H26ClN7O3/c1-34-19-6-5-15(10-18(19)24)11-27-21-17(22(33)28-13-20-25-7-3-8-26-20)12-29-23(30-21)31-9-2-4-16(31)14-32/h3,5-8,10,12,16,32H,2,4,9,11,13-14H2,1H3,(H,28,33)(H,27,29,30)/t16-/m0/s1
(3)InChIKey: WEAJZXNPAWBCOA-INIZCTEOBD

Product Name

Avanafil

Synthetic route

Avanafil Specification

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