73963-42-5

Basic information

• Product Name: 5-(4-Chlorobutyl)-1-cyclohexanyl tetrazole
• Synonyms: 5-(4-CHLOROBUTYL)-1-CYCLOHEXYLTETRAZOLE HYDROCHLORIDE;6-HYDROXY-3,4-DIHYDRO-1H-QUINOLIN-2-ONE;6-HYDROXY-3,4-DIHYDROQUINOLIN-2(1H)-ONE;6-HYDROXY-3,4-DIHYDROQUINOLONE;6-HYDROXYL-3,4-DIHYDROCARBOSTYRIL;6-HYDROXY-1,2,3,4-TETRAHYDRO-2-QUINOLINONE;6-HQ;6-HYDROXY-3,4-DIHYDRO-2-QUINOLINONE
• CAS NO: 73963-42-5
• Molecular Formula: C₁₁H₁₉ClN₄
• Molecular Weight: 242.75
• Product Categories: Tetrazoles;(intermediate of cilostazol);Heterocycles
• Mol File: 73963-42-5.mol
• Article Data: 5

Chemical Properties

• Melting Point: 49-52°C
• Boiling Point: 425.2 °C at 760 mmHg
• Flash Point: 210.9 °C
• Appearance: white solid
• Density: 1.29 g/cm³
• Vapor Pressure: 1.95E-07mmHg at 25°C
• Refractive Index: 1.622
• Storage Temp.: -20°C Freezer
• PKA: 1.23±0.10(Predicted)
• CAS DataBase Reference: 5-(4-Chlorobutyl)-1-cyclohexanyl tetrazole(CAS DataBase Reference)
• NIST Chemistry Reference: 5-(4-Chlorobutyl)-1-cyclohexanyl tetrazole(73963-42-5)
• EPA Substance Registry System: 5-(4-Chlorobutyl)-1-cyclohexanyl tetrazole(73963-42-5)

Safety Data

• Hazard Codes: Xi
• Hazardous Substances Data: 73963-42-5(Hazardous Substances Data)

Usage

Chemical Properties

White Solid

Uses

Different sources of media describe the Uses of 73963-42-5 differently. You can refer to the following data:
1. An impurity of Cilostazol.
2. An impurity of Cilostazol (C441500(P)), which is a potent phosphodiesterase III A (PDE3A) inhibitor (IC50=0.2uM) and inhibitor of adenosine uptake. Has antimitogenic, antithrombotic, vasodilatory and cardiotonic properties and affects lipid levels in vivo.

InChI:InChI=1/C11H19ClN4/c12-9-5-4-8-11-13-14-15-16(11)10-6-2-1-3-7-10/h10H,1-9H2

Synthetic route

N-(5-chloro-n-pentanoyl)cyclohexylamine (15865-18-6) → 1-cyclohexyl-5-(4-chlorobutyl)-1,2,3,4-tetrazole (73963-42-5)

Conditions	Yield
Stage #1: N-(5-chloro-n-pentanoyl)cyclohexylamine With phosphorus pentachloride In toluene at 20℃; for 3h; Stage #2: With trimethylsilylazide at 20℃; for 16h;	93%
With tris-(2-chloro-ethyl)-amine; phosphorus pentachloride 1.) r.t., 1 h, benzene, 2.) benzene, r.t., reflux, 2 h; Yield given. Multistep reaction;
Stage #1: N-(5-chloro-n-pentanoyl)cyclohexylamine With chloro-trimethyl-silane; sodium azide In toluene at 20℃; for 0.833333h; Inert atmosphere; Stage #2: With phosphorus pentachloride In toluene at 0 - 55℃;	56 g

5-chloro-valeric acid (1119-46-6) + cyclohexylamine (108-91-8) → 1-cyclohexyl-5-(4-chlorobutyl)-1,2,3,4-tetrazole (73963-42-5)

Conditions	Yield
With trimethylsilylazide; trichlorophosphate In acetonitrile at 120℃; for 0.166667h; Microwave irradiation;	65%

phosphorus pentachloride (10026-13-8, 874483-75-7) + N-(5-chloro-n-pentanoyl)cyclohexylamine (15865-18-6) → 1-cyclohexyl-5-(4-chlorobutyl)-1,2,3,4-tetrazole (73963-42-5)

Conditions	Yield
With hydrogen azide In ethyl acetate; benzene

3,4-dihydro-6-hydroxy-2(1H)-quinolinone (54197-66-9) + 1-cyclohexyl-5-(4-chlorobutyl)-1,2,3,4-tetrazole (73963-42-5) → 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydrocarbostyril (73963-72-1)

Conditions	Yield
With potassium carbonate; sodium hydroxide; sodium sulfite In ethanol for 8h; Reflux;	92.5%
With potassium carbonate; sodium hydroxide; sodium sulfite In water at 92℃; for 6h; Solvent; Reagent/catalyst; Temperature;	91.5%
With potassium hydroxide In ethanol at 80℃; for 12h; Solvent; Reagent/catalyst; Temperature; Inert atmosphere; Sealed tube;	90%

1-cyclohexyl-5-(4-chlorobutyl)-1,2,3,4-tetrazole (73963-42-5) → 1-cyclohexyl-5-(4-chlorobutyl)tetrazole-3-oxide (1221230-57-4)

Conditions	Yield
With acetonitrile complex of hypofluorous acid In dichloromethane at 0℃;	90%

3-bromo-4-nitrophenol (5470-65-5) + 1-cyclohexyl-5-(4-chlorobutyl)-1,2,3,4-tetrazole (73963-42-5) → C17H22BrN5O3

Conditions	Yield
With sodium hydroxide In butan-1-ol for 8h; Reagent/catalyst; Solvent; Reflux;	90%

3,4-dihydro-6-hydroxy-2(1H)-quinolinone (54197-66-9) + 1-cyclohexyl-5-(4-chlorobutyl)-1,2,3,4-tetrazole (73963-42-5) → 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)-butoxy]-1-[4-(1-cyclohexyl-1H-tetrazol-5-yl)-butyl]-3,4-dihydro-1H-quinolin-2-one (865792-18-3) + 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydrocarbostyril (73963-72-1) + OPC 13015 (73963-62-9)

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In ethanol at 75 - 80℃;	A n/a B 89% C n/a

5-hydroxy-2-nitrobenzaldehyde ethylene acetal (98454-56-9) + 1-cyclohexyl-5-(4-chlorobutyl)-1,2,3,4-tetrazole (73963-42-5) → 5-<4-(1-cyclohexy-1H-5-tetrazolyl)butoxy>-2-nitrobenzaldehyde ethylene acetal (98454-57-0)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 120℃; for 6h;	87%

6-hydroxy-1H-quinolin-2-one (19315-93-6) + 1-cyclohexyl-5-(4-chlorobutyl)-1,2,3,4-tetrazole (73963-42-5) → OPC 13015 (73963-62-9)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 7h;	85%
With potassium hydroxide In isopropyl alcohol for 4h; Heating;	37%

6-hydroxyquinoline (580-16-5) + 1-cyclohexyl-5-(4-chlorobutyl)-1,2,3,4-tetrazole (73963-42-5) → 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]quinoline (1140833-77-7)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 7h;	80%

6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-1-hydroxyquinolin-2-one (1140833-81-3) + 1-cyclohexyl-5-(4-chlorobutyl)-1,2,3,4-tetrazole (73963-42-5) → 1,6-bis[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-1H-quinolin-2-one (1140833-72-2)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 7h;	75%

4-(4-chloropyridin-2-yl)morpholine + 1-cyclohexyl-5-(4-chlorobutyl)-1,2,3,4-tetrazole (73963-42-5) → 4-(4-(4-(1-cyclohexyl-1H-tetrazol-5-yl)butyl)pyridin-2-yl)morpholine

Conditions	Yield
With 2,2'-biimidazole; (1,2-dimethoxyethane)dichloronickel(II); (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(2-phenylpyridine(-1H))-iridium(III) hexafluorophosphate; N-(adamantan-1-yl)-1,1,1,3,3,3-hexamethyl-2-(trimethylsilyl)trisilan-2-amine; N,N,N',N'-tetramethylguanidine In tert-Amyl alcohol; N,N-dimethyl acetamide at 50 - 55℃; for 18h; Inert atmosphere; Irradiation;	64%

1-cyclohexyl-5-(4-chlorobutyl)-1,2,3,4-tetrazole (73963-42-5) → 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydrocarbostyril (73963-72-1)

Conditions	Yield
Stage #1: 3,4-dihydro-6-hydroxy-2(1H)-quinolinone With 1,8-diazabicyclo[5.4.0]undec-7-ene In ethanol for 6.5h; Heating / reflux; Molecular sieve; Stage #2: 1-cyclohexyl-5-(4-chlorobutyl)-1,2,3,4-tetrazole In ethanol for 6.5h; Product distribution / selectivity; Heating / reflux;	40.2%
Multi-step reaction with 4 steps 1: sodium hydroxide / butan-1-ol / 8 h / Reflux 2: iron; ammonium chloride; acetic acid / methanol; water / 5 h / 45 °C / Reflux 3: triethylamine / dichloromethane / 3 h / 0 °C 4: N-ethyl-N,N-diisopropylamine; tetrakis(triphenylphosphine) palladium(0) / acetonitrile / 10 h / Inert atmosphere; Reflux View Scheme

1-cyclohexyl-5-(4-chlorobutyl)-1,2,3,4-tetrazole (73963-42-5) + C8(14)CH9NO2 → C19(14)CH27N5O2

6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydrocarbostyril (73963-72-1) + 1-cyclohexyl-5-(4-chlorobutyl)-1,2,3,4-tetrazole (73963-42-5) → 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)-butoxy]-1-[4-(1-cyclohexyl-1H-tetrazol-5-yl)-butyl]-3,4-dihydro-1H-quinolin-2-one (865792-18-3)

Conditions	Yield
With sodium hydride In DMF (N,N-dimethyl-formamide) at 10 - 15℃; for 27.5h;

1-cyclohexyl-5-(4-chlorobutyl)-1,2,3,4-tetrazole (73963-42-5) → C17H24BrN5O

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide / butan-1-ol / 8 h / Reflux 2: iron; ammonium chloride; acetic acid / methanol; water / 5 h / 45 °C / Reflux View Scheme

1-cyclohexyl-5-(4-chlorobutyl)-1,2,3,4-tetrazole (73963-42-5) → C20H26BrN5O2

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium hydroxide / butan-1-ol / 8 h / Reflux 2: iron; ammonium chloride; acetic acid / methanol; water / 5 h / 45 °C / Reflux 3: triethylamine / dichloromethane / 3 h / 0 °C View Scheme

Upstream product

• 1119-46-6 5-chloro-valeric acid 
• 108-91-8 cyclohexylamine 
• 10026-13-8 phosphorus pentachloride 
• 15865-18-6 N-(5-chloro-n-pentanoyl)cyclohexylamine 

Downstream Products

• 1221230-57-4 1-cyclohexyl-5-(4-chlorobutyl)tetrazole-3-oxide 
• 1140833-72-2 1,6-bis[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-1H-quinolin-2-one 
• 1140833-77-7 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]quinoline 
• 865792-18-3 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)-butoxy]-1-[4-(1-cyclohexyl-1H-tetrazol-5-yl)-butyl]-3,4-dihydro-1H-quinolin-2-one 
• 73963-72-1 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydrocarbostyril 
• 73963-62-9 OPC 13015 
• 98454-57-0 5-<4-(1-cyclohexy-1H-5-tetrazolyl)butoxy>-2-nitrobenzaldehyde ethylene acetal 

Relevant articles and documents

Synthesis method of N-cyclohexyl-5-(4-chlorobutyl)-1H-tetrazole

The invention discloses a synthesis method of N-cyclohexyl-5-(4-chlorobutyl)-1H-tetrazole. The synthesis method comprises the following steps: firstly, synthesizing N, N-dimethylformamide; the synthesis method comprises the following synthesis steps: taking 5-chlorovaleronitrile and cyclohexanol as raw materials, controlling the molar ratio of the 5-chlorovaleronitrile to the cyclohexanol to be (1: 1)-(1: 1.5) and the reaction temperature to be 5-55 DEG C, and carrying out a catalytic reaction for 1-6 hours by virtue of concentrated sulfuric acid, so as to obtain 5-chloro-N-cyclohexylvaleramide; wherein the molar ratio of the 5-chlorovaleronitrile to the concentrated sulfuric acid for catalysis is (1: 3)-(1: 10); the preparation method comprises the following steps: treating 1, 5-chloro-N-cyclohexylvaleric amide with phosphorus pentachloride; wherein the molar ratio of the 3, 5-chloro-N-cyclohexylvaleric amide to the phosphorus pentachloride is (1: 1)-(1: 1.5) and the molar ratio of the 2, 5-chloro-N-cyclohexylvaleric amide to the phosphorus pentachloride is (1: 1)-(1: 1.5); according to the invention, trimethyl silicon azide is used as a cyclization reagent instead of azoic acid or sodium azide, so that the synthesis method has the advantages of higher stability, no explosion and higher safety, the cost can be effectively reduced, the synthesis method is environment-friendly,and the purity of the obtained product is high.

A PROCESS FOR THE PREPARATION OF CILOSTAZOL AND OF THE INTERMEDIATES THEREOF

A process for the preparation of compounds of formula (III), intermediates useful for the synthesis of cilostazol, which process comprises reacting haloimine of formula (V) wherein X is halogen, with trimethylsilyl azide.

Studies on 2-oxoquinoline derivatives as blood platelet aggregation inhibitors. II. 6-[3-(1-Cyclohexyl-5-tetrazolyl)propoxy]-1,2-dihydro-2-oxoquinoline and related compounds

A series of ω-(1-substituted-5-tetrazolylalkoxy)-2-oxoquinolines was synthesized and tested for inhibitory activity towards collagen- and adenosine diphosphate (ADP)-induced aggregation of rabbit blood platelets in vitro. These compounds were prepared by the reaction of 1-substituted-5-(ω-chloroalkyl)-tetrazoles and hydroxy-2-oxoquinolines in the presence of a base. Among them, 6-[3-(1-cyclohexyl-5-tetrazolyl)propoxy]-1,2-dihydro-2-oxoquinoline (IVb) was found to have the most potent inhibitory activity. The structure-activity relationships are discussed.