74050-98-9

Basic information

• Product Name: Ketanserin
• Synonyms: 3-[2-[4-(4-fluorobenzoyl)-1-piperidinyl]ethyl]-2,4[1h,3h]-quinazolinedione;KETANSERIN;3-[2-[4-(4-Fluorobenzoyl)-1-piperidinyl]ethyl]-2，4-(IH，3H)-quinazolinedione;Ket;Ketensin;Perketan;R-49945;Serefrex
• CAS NO: 74050-98-9
• Molecular Formula: C₂₂H₂₂FN₃O₃
• Molecular Weight: 395.43
• EINECS: 277-680-2
• Product Categories: ketone;Intermediates & Fine Chemicals;Pharmaceuticals;Other APIs
• Mol File: 74050-98-9.mol
• Article Data: 4

Chemical Properties

• Melting Point: 227-235°C
• Appearance: /
• Density: 1.281 g/cm³
• Refractive Index: 1.592
• Storage Temp.: 2-8°C
• Solubility: DMF: 10 mg/mL, clear, colorless
• PKA: 7.5(at 25℃)
• Merck: 14,5296
• CAS DataBase Reference: Ketanserin(CAS DataBase Reference)
• NIST Chemistry Reference: Ketanserin(74050-98-9)
• EPA Substance Registry System: Ketanserin(74050-98-9)

Safety Data

• WGK Germany: 3
• RTECS: VA1411190
• Hazardous Substances Data: 74050-98-9(Hazardous Substances Data)

Usage

Description

Ketanserin is an antihypertensive agent with antagonist properties at both the serotonin-S2 and α1-adrenergic receptors. Its mechanism of action, while still controversial, may involve interactions at both of these loci.

Chemical Properties

Off-White Solid

Originator

Janssen (Belgium)

Uses

An antihypertensive, with affinity for multiple GPCR receptors.

Definition

ChEBI: A member of the class of quinazolines that is quinazoline-2,4(1H,3H)-dione which is substituted at position 3 by a 2-[4-(p-fluorobenzoyl)piperidin-1-yl]ethyl group.

Brand name

SEREFREX

Purification Methods

It has been purified by recrystallisation from 4-methyl-3-pentanone [Peeters et al. Cryst Structure Commun 11 375 1982, Kacprowicz et al. J Chromatogr 272 417 1983, Davies et al. J Chromatogr 275 232 1983]. It is an antihypertensive.

InChI:InChI=1/C22H22FN3O3/c23-17-7-5-15(6-8-17)20(27)16-9-11-25(12-10-16)13-14-26-21(28)18-3-1-2-4-19(18)24-22(26)29/h1-8,16H,9-14H2,(H,24,29)

Synthetic route

(4-fluorophenyl)-piperidin-4-ylmethanone (56346-57-7) + 3-(2-chloroethyl)-2,4-dioxo-1,2,3,4-tetrahydroquinazoline (5081-87-8) → ketanserine (74050-98-9)

Conditions	Yield
With sodium carbonate In butanone for 24h; Reflux;	86%

(4-fluorophenyl)-piperidin-4-ylmethanone (56346-57-7) + 2,3-dihydro-5H-oxazolo<2,3-b>quinazolin-5-one (52727-44-3) → ketanserine (74050-98-9)

Conditions	Yield
In neat (no solvent) at 110℃;	85%
In toluene for 40h; Reflux;	80%

4-(4-fluorobenzoyl)piperidine hydrochloride (25519-78-2) + 4-methyl-2-pentanone (108-10-1) + 3-(2-chloroethyl)-2,4-dioxo-1,2,3,4-tetrahydroquinazoline (5081-87-8) → ketanserine (74050-98-9)

Conditions	Yield
With sodium carbonate In water	2,2 parts (27%)

2,4-Dioxo-3-(2-hydroxyethyl)-1,2,3,4-tetrahydroquinazoline (1207-75-6) → ketanserine (74050-98-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: thionyl chloride / chloroform / 4 h / Reflux 2: sodium carbonate / butanone / 24 h / Reflux View Scheme
Multi-step reaction with 3 steps 1: thionyl chloride / 1,2-dichloro-ethane / 2 h / 20 - 80 °C 2: sodium carbonate / acetonitrile / 7 h / 85 °C 3: toluene / 40 h / Reflux View Scheme

4-(4-fluorobenzoyl)piperidine hydrochloride (25519-78-2) → ketanserine (74050-98-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium carbonate / methanol / 4 h / 20 °C 2: neat (no solvent) / 110 °C View Scheme
Multi-step reaction with 2 steps 1: sodium carbonate / methanol / 4 h / 20 °C 2: sodium carbonate / butanone / 24 h / Reflux View Scheme

2-ethoxycarbonylaniline (87-25-2) → ketanserine (74050-98-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: chloroform / 0.5 h / 50 °C 1.2: 4 h / 150 °C 2.1: sodium carbonate / butanone / 24 h / Reflux View Scheme
Multi-step reaction with 4 steps 1: chloroform / 50 °C 2: chloroform / 4 h / 150 °C 3: thionyl chloride / chloroform / 4 h / Reflux 4: sodium carbonate / butanone / 24 h / Reflux View Scheme

ethyl (2-ethoxycarbonyl)phenylcarbamate (108890-73-9) → ketanserine (74050-98-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: chloroform / 4 h / 150 °C 2: thionyl chloride / chloroform / 4 h / Reflux 3: sodium carbonate / butanone / 24 h / Reflux View Scheme

2-carbomethoxyaniline (134-20-3) → ketanserine (74050-98-9)

Conditions	Yield
Multi-step reaction with 5 steps 1: sodium carbonate / tetrahydrofuran; water / 12 h / -5 - 20 °C 2: 5,5-dimethyl-1,3-cyclohexadiene / 12 h / 140 °C 3: thionyl chloride / 1,2-dichloro-ethane / 2 h / 20 - 80 °C 4: sodium carbonate / acetonitrile / 7 h / 85 °C 5: toluene / 40 h / Reflux View Scheme

methyl 2-((ethoxycarbonyl)amino)benzoate (83846-67-7) → ketanserine (74050-98-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: 5,5-dimethyl-1,3-cyclohexadiene / 12 h / 140 °C 2: thionyl chloride / 1,2-dichloro-ethane / 2 h / 20 - 80 °C 3: sodium carbonate / acetonitrile / 7 h / 85 °C 4: toluene / 40 h / Reflux View Scheme

ketanserine (74050-98-9) + tartaric acid (87-69-4) → ketanserin tartrate (83846-83-7, 97987-92-3, 121322-28-9, 129046-76-0)

Conditions	Yield
In ethanol	100%

tetrafluoroboric acid diethyl ether (67969-82-8) + 2,3,7,8-tetrafluorothianthrene-S-oxide + ketanserine (74050-98-9) → C34H25F5N3O3S2(1+)*BF4(1-)

Conditions	Yield
With 2,3,7,8-tetrafluorothianthrene; trifluoroacetic anhydride In acetonitrile at 0 - 25℃; regioselective reaction;	60%

tetrafluoroboric acid diethyl ether (67969-82-8) + sodium tetrafluoroborate (13755-29-8) + 2,3,7,8-tetrafluorothianthrene-S-oxide + ketanserine (74050-98-9) → C34H25F5N3O3S2(1+)*BF4(1-)

Conditions	Yield
Stage #1: tetrafluoroboric acid diethyl ether; 2,3,7,8-tetrafluorothianthrene-S-oxide; ketanserine With trifluoroacetic anhydride In acetonitrile at 0 - 25℃; for 2h; Stage #2: sodium tetrafluoroborate In dichloromethane; water	60%

ethereal hydrogen chloride + ketanserine (74050-98-9) + 2-chloro-N,N-dimethylacetamide (2675-89-0) → 2-[3-{2-[4-(4-Fluorobenzoyl)-1-piperidinyl]ethyl}-2,4-dioxo-3,4-dihydro-1(2H)-quinazolinyl]-N,N-dimethylacetamide hydrochloride (298696-31-8)

Conditions	Yield
With NaH In N,N-dimethyl-formamide; mineral oil

ketanserine (74050-98-9) → Ketanserinol

Conditions	Yield
With sodium borohydrid In methanol; water

Upstream product

• 25519-78-2 4-(4-fluorobenzoyl)piperidine hydrochloride 
• 108-10-1 4-methyl-2-pentanone 
• 5081-87-8 3-(2-chloroethyl)-2,4-dioxo-1,2,3,4-tetrahydroquinazoline 
• 1207-75-6 2,4-Dioxo-3-(2-hydroxyethyl)-1,2,3,4-tetrahydroquinazoline 
• 56346-57-7 (4-fluorophenyl)-piperidin-4-ylmethanone 
• 52727-44-3 2,3-dihydro-5H-oxazolo<2,3-b>quinazolin-5-one 
• 87-25-2 2-ethoxycarbonylaniline 
• 108890-73-9 ethyl 2-((ethoxycarbonyl)amino)benzoate 
• 83846-67-7 methyl 2-((ethoxycarbonyl)amino)benzoate 
• 134-20-3 2-carbomethoxyaniline 

Downstream Products

• 298696-31-8 2-[3-{2-[4-(4-Fluorobenzoyl)-1-piperidinyl]ethyl}-2,4-dioxo-3,4-dihydro-1(2H)-quinazolinyl]-N,N-dimethylacetamide hydrochloride 
• 83846-83-7 ketanserin tartrate 
• 76330-73-9 Ketanserinol 

Relevant articles and documents

Ketoserin intermediate and preparation method of ketoserin

The invention discloses a preparation method of a ketoserin intermediate 2, 3-dihydro-5H-oxazolo[2, 3-B]quinazoline-5-ketone and a preparation method of ketoserin, and the reaction equation of the preparation method of the ketoserin intermediate 2, 3-dihydro-5H-oxazolo[2, 3-B]quinazoline-5-ketone is shown in the specification: in the reaction, sodium carbonate and acetonitrile are used, no catalyst is added, inorganic salt is removed through hot filtration after the reaction, filtrate is evaporated to dryness, acetonitrile is recycled, and an intermediate 04, namely the ketoserin intermediate2, 3-dihydro-5H-oxazolo[2, 3-B]quinazoline-5-ketone, is obtained. The method is simple and convenient to operate, lower in cost, better in product character and more beneficial to synthesis of a finalproduct.

Floating pharmaceutical composition comprising an active phase and a non-active phase

The invention concerns a floating pharmaceutical composition consisting of at least a first phase comprising at least a high dose active principle combined with one or several carriers and at least a second phase comprising at least a gas-generating system. The invention also concerns tablets comprising such a pharmaceutical composition and a method for preparing such tablets.