13908-11-7

Usage

Uses

1. Used in Pharmaceutical Synthesis:
1-CYCLOHEXYL-3-(2-CHLOROETHYL)UREA is used as a reagent for the synthesis of lomustine, a chemotherapy drug. Its role in the synthesis process is essential for the production of effective cancer treatments.
2. Used in Antitumor Agent Development:
1-CYCLOHEXYL-3-(2-CHLOROETHYL)UREA is used as a precursor in the synthesis of N-nitrosoureas and N-nitrosothiourea, which are potential antitumor agents. These compounds have shown promise in the development of new cancer therapies.
3. Used in the Chemical Industry:
In the chemical industry, 1-CYCLOHEXYL-3-(2-CHLOROETHYL)UREA is used as an intermediate for the production of various chemicals and pharmaceuticals. Its unique structure allows for further modification and synthesis of a wide range of compounds with diverse applications.
4. Used in Research and Development:
1-CYCLOHEXYL-3-(2-CHLOROETHYL)UREA is utilized in research and development for the exploration of new chemical reactions and the discovery of novel compounds with potential applications in various fields, including medicine, agriculture, and materials science.

Synthetic route

2-chloroethyl isothiocyanate (1943-83-5) + cyclohexylamine (108-91-8) → N-(2-chloroethyl)-N'-cyclohexylurea (13908-11-7)

Conditions	Yield
With triethylamine In tetrahydrofuran at 50℃; for 0.0166667h; Solvent; Temperature; Time; Flow reactor;	91.7%
With triethylamine In tetrahydrofuran at 50℃; for 0.0166667h; Solvent; Temperature;	91.7%
With diethyl ether

N-cyclohexyl-carbamate de succinimidyle (80672-61-3) + chloroethylamine (689-98-5) → N-(2-chloroethyl)-N'-cyclohexylurea (13908-11-7)

Conditions	Yield
Ambient temperature;	68.6%

Hexamethylendi- (34693-48-6) + cyclohexylamine (108-91-8) → N-(2-chloroethyl)-N'-cyclohexylurea (13908-11-7)

Ethyl-5-(2-chloroethyl)-3-nitrosohydantoat (60285-28-1) + cyclohexylamine (108-91-8) → N-(2-chloroethyl)-N'-cyclohexylurea (13908-11-7)

Conditions	Yield
In water Ambient temperature;

1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (13010-47-4) → Diazoethan (1117-96-0) + N-(2-chloroethyl)-N'-cyclohexylurea (13908-11-7) + ethanol (64-17-5) + cyclohexylamine (108-91-8) + ethylamine (75-04-7) + 2-chlorodiazomethane

Conditions	Yield
With potassium hydroxide; aluminum nickel In methanol Product distribution; Mechanism; degradation under various conditions (HBr in glac. CH3CO2H) with preparation of nonmutagenic reaction mixtures of products;

Cyclohexyl isocyanate (3173-53-3) + chloroethylamine (689-98-5) → N-(2-chloroethyl)-N'-cyclohexylurea (13908-11-7)

Conditions	Yield
In diethyl ether Ambient temperature;

cyclohexylamine (108-91-8) → N-(2-chloroethyl)-N'-cyclohexylurea (13908-11-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 56.6 percent / acetonitrile / Ambient temperature 2: 68.6 percent / Ambient temperature View Scheme

N-(2-chloroethyl)-N'-cyclohexylurea (13908-11-7) → 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (13010-47-4)

Conditions	Yield
With tin(IV) chloride; sodium nitrite In dichloromethane at 20℃; for 2h;	100%
With tert.-butylnitrite In ethanol; acetonitrile at 25℃; for 0.133333h; Reagent/catalyst; Solvent; Temperature; Time; Flow reactor;	91.2%
With tert.-butylnitrite In ethanol; acetonitrile at 25℃; for 0.133333h; Reagent/catalyst; Temperature; Solvent;	91.2%

N-(2-chloroethyl)-N'-cyclohexylurea (13908-11-7) → 2-(cyclohexylamino)-2-oxazoline (10002-37-6)

Conditions	Yield
In water Heating;	80%

Upstream product

• 3173-53-3 Cyclohexyl isocyanate 
• 689-98-5 chloroethylamine 
• 80672-61-3 N-cyclohexyl-carbamate de succinimidyle 
• 108-91-8 cyclohexylamine 
• 13010-47-4 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea 
• 1943-83-5 2-chloroethyl isothiocyanate 
• 60285-28-1 Ethyl-5-(2-chloroethyl)-3-nitrosohydantoat 
• 34693-48-6 Hexamethylendi- 

Downstream Products

• 13010-47-4 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea 
• 10002-37-6 2-(cyclohexylamino)-2-oxazoline 

Relevant academic research and scientific papers

On-Demand Rapid Synthesis of Lomustine Under Continuous Flow Conditions

Disclosed herein is a continuous manufacturing process for lomustine that has a short residence time and 63 percent yield. Major advantages of this process are that the total production cost for lomustine is lower, the product is higher quality, and the manufacturing operation is safer for production personnel.

Rapid On-Demand Synthesis of Lomustine under Continuous Flow Conditions

Lomustine, an important agent for treatment of brain tumors and Hodgkin's lymphoma, has been synthesized using continuous flow methodology. Desorption electrospray ionization mass spectrometry (DESI-MS) was used to quickly explore a large number of reaction conditions for one of the reaction steps and guide the efficient translation of optimized conditions to continuous lomustine production. Using only four inexpensive commercially available starting materials and a total residence time of 9 min, lomustine was prepared via a linear sequence of two chemical reactions performed separately in two telescoped flow reactors. Sequential offline extraction and filtration resulted in a 63% overall yield of pure lomustine at a production rate of 110 mg/h. The primary advantages of this approach are the rapid manufacture of lomustine with two telescoped steps to avoid isolation and purification of a labile intermediate and the mild conditions used in the nitrosylation step, thereby significantly increasing the purity and yield of this active pharmaceutical ingredient.

Degradation and disposal of some antineoplastic drugs

Bulk quantities and pharmaceutical preparations of the antineoplastic drugs carmustine (BCNU), lomustine (CCNU), chlorozotocin, N-[2-chloroethyl]-N'-[2,6-dioxo-3-piperidinyl]-N-nitrosourea (PCNU), methyl CCNU, mechlorethamine, melphalan, chlorambucil, cyclophosphamide, ifosfamide, uracil mustard, and spiromustine may be degraded using nickel-aluminium alloy in KOH solution. The drugs are completely destroyed and only nonmutagenic reaction mixtures are produced. destruction of cyclophosphamide in tablets requires refluxing in HCl before the nickel-aluminium alloy reduction. Streptozotocin, chlorambucil, and mechlorethamine may be degraded using an excess of saturated bicarbonate solution. The nitrosourea drugs BCNU, CCNU, chlorozotocin, PCNU, methyl CCNU, and streptozotocin were also degraded using hydrogen bromide in glacial acetic acid. The drugs were completely destroyed but some of the reaction mixtures were mutagenic and the products were found to be, in some instances, the corresponding mutagenic, denitrosated compounds.

Convenient Methods for Syntheses of Active Carbamates, Ureas and Nitrosoureas Using N,N'-disuccinimido Carbonate (DSC)

The reaction of DSC and amino compounds afforded the corresponding carbamates which were able to be converted into ureas and nitrosoureas.