917342-29-1

Basic information

• Product Name: CarbaMic acid, N-[trans-4-(2-hydroxyethyl)cyclohexyl]-, 1,1-diMethylethyl ester
• Synonyms: CarbaMic acid, N-[trans-4-(2-hydroxyethyl)cyclohexyl]-, 1,1-diMethylethyl ester;trans-1-(Boc-aMino)-4-(2-hydroxyethyl)cyclohexane, 97%;N-[trans-4-(2-hydroxyethyl)cyclohexyl]-, 1,1-diMethylethyl esterCarbaMic acid;trans-2-[4-[(tert-Butoxycarbonyl)amino]cyclohexyl]ethanol
• CAS NO: 917342-29-1
• Molecular Formula: C₁₃H₂₅NO₃
• Molecular Weight: 243.3425
• Mol File: 917342-29-1.mol
• Article Data: 5

Chemical Properties

• Boiling Point: 366.0±11.0 °C(Predicted)
• Appearance: /
• Density: 1.03±0.1 g/cm3(Predicted)
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 12.56±0.40(Predicted)
• CAS DataBase Reference: CarbaMic acid, N-[trans-4-(2-hydroxyethyl)cyclohexyl]-, 1,1-diMethylethyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: CarbaMic acid, N-[trans-4-(2-hydroxyethyl)cyclohexyl]-, 1,1-diMethylethyl ester(917342-29-1)
• EPA Substance Registry System: CarbaMic acid, N-[trans-4-(2-hydroxyethyl)cyclohexyl]-, 1,1-diMethylethyl ester(917342-29-1)

Safety Data

• Hazardous Substances Data: 917342-29-1(Hazardous Substances Data)

Usage

Description

CarbaMic acid, N-[trans-4-(2-hydroxyethyl)cyclohexyl]-, 1,1-dimethylethyl ester is a chemical compound with a unique structure that features a carbamic acid group attached to a trans-4-(2-hydroxyethyl)cyclohexyl moiety. This ester derivative is known for its potential applications in the synthesis of various pharmaceutical compounds.

Uses

Used in Pharmaceutical Industry:
CarbaMic acid, N-[trans-4-(2-hydroxyethyl)cyclohexyl]-, 1,1-dimethylethyl ester is used as an intermediate in the synthesis of quinolinones and their analogs for treating multi-drug resistant bacterial infections. Its unique structure allows for the development of novel antibiotics that can overcome the resistance mechanisms of various bacteria.
Additionally, this compound is used as a precursor in the preparation of the antipsychotic drug Cariprazine. Cariprazine is a second-generation antipsychotic medication used to treat schizophrenia and bipolar disorder, and its synthesis involves the use of CarbaMic acid, N-[trans-4-(2-hydroxyethyl)cyclohexyl]-, 1,1-dimethylethyl ester.
Furthermore, CarbaMic acid, N-[trans-4-(2-hydroxyethyl)cyclohexyl]-, 1,1-dimethylethyl ester is utilized in the synthesis of C-2 hydroxyethyl imidazopyrrolo pyridines, which are JAK1 inhibitors. These inhibitors play a crucial role in the treatment of various inflammatory and autoimmune diseases by targeting the Janus kinase (JAK) family of enzymes.
Lastly, this compound is also used in the preparation of Mer kinase inhibitors, which are being developed for the treatment of pediatric acute lymphoblastic leukemia. The development of these inhibitors aims to provide more effective and targeted therapies for this type of cancer, improving patient outcomes and survival rates.

Synthesis

An 500 ml four-necked flask is charged with 40 g (0,18 mol) of trans 2-[1-(4-amino]- cyclohexyl)-acetic acid ethyl ester hydrochloride and 160 ml of dichloromethane. To the resulting suspension 18,2 g (0,18 mol) of triethylamine is added. The reaction mixture is cooled to a temperature between 8-10°C and a solution of 40,0 g (0,185 mol) of di(tert-butyl)dicarbonate in 100 ml of dichloromethane is added for 1 hour with stirring under nitrogen. Then the reaction mixture is allowed to warm to a temperature between 22-25°C and stirred until the reaction proceeds. After completion of the reaction 100 g of 5% aqueous sodium carbonate is added and the phases are separated. The organic layer is extracted with 50 ml of water and after separation the organic layer is dried under Na2SO4 and the filtrate is concentrated in vacuum. The trans 2-{1-[4-(N-tert-butoxycarbonyl)-amino]-cyclohexyl}-acetic acid ethyl ester obtained is dissolved in 460 ml of tetrahydrofurane then 13,68 g (0,36 mol) of sodium borohydride is added at 25°C under nitrogen. With stirring, to the reaction mixture a solution of 24,0 g (0,18 mol) of aluminium chloride in 250 ml abs. tetrahydrofurane is added dropwise at a temperature between 18-22°C for 1 hour under nitrogen then the mixture is stirred for additional 2 hours. After completion of the reaction the mixture is cooled to a temperature between 5-10°C and 650 ml of water and 600 ml of toluene are added. Then the pH was adjusted to 3-4 by adding 40-45 ml of concentrated hydrochloric acid and the stirring was continued at a temperature between 20-25°C for 1 hour. The phases are separated, the aqueous layer is extracted with 50 ml of toluene and the combined organic layers are washed with 3×150 ml of water and dried in vacuum. In this manner 41,1 g of title compound was obtained. Yield: 94% 20. Melting point: 101-103°C.

Upstream product

• 215789-45-0 trans-2-(1-(4-(N-tert-butoxycarbonyl)amino)cyclohexyl)acetic acid methyl ester 
• 946598-34-1 trans 2-{1-[4-(N-(tert-butoxycarbonyl))amino]cyclohexyl}ethyl acetate 
• 179321-49-4 N-(tert-butoxycarbonyl)-4-aminocyclohexanone 

Downstream Products

• 1062468-06-7 trans-tert-butyl-4-(2-bromoethyl)cyclohexylcarbamate 
• 506427-91-4 trans N-tert-butoxycarbonyl-4-{2-[4-(2,3-dichlorophenyl)-piperazin-1-yl]ethyl}-cyclohexylamine 
• 839712-12-8 Cariprazine 
• 2093293-77-5 trans (2-(1-[4-(N-(tert-butoxycarbonyl))-amino]-cyclohexyl))ethyl 4-methylbenzenesulfonate 
• 215790-29-7 trans-2-(1-(4-(N-tert-butoxycarbonyl)amino)cyclohexyl)acetaldehyde 

Relevant articles and documents

Exception That Proves the Rule: Investigation of Privileged Stereochemistry in Designing Dopamine D3R Bitopic Agonists

In this study, starting from our selective D3R agonist FOB02-04A (5), we investigated the chemical space around the linker portion of the molecule via insertion of a hydroxyl substituent and ring-expansion of the trans-cyclopropyl moiety into a trans-cyclohexyl scaffold. Moreover, to further elucidate the importance of the primary pharmacophore stereochemistry in the design of bitopic ligands, we investigated the chiral requirements of (+)-PD128907 ((+)-(4aR,10bR)-2)) by synthesizing and resolving bitopic analogues in all the cis and trans combinations of its 9-methoxy-3,4,4a,10b-tetrahydro-2H,5H-chromeno[4,3-b][1,4] oxazine scaffold. Despite the lack of success in obtaining new analogues with improved biological profiles, in comparison to our current leads, a "negative"result due to a poor or simply not improved biological profile is fundamental toward better understanding chemical space and optimal stereochemistry for target recognition. Herein, we identified essential structural information to understand the differences between orthosteric and bitopic ligand-receptor binding interactions, discriminate D3R active and inactive states, and assist multitarget receptor recognition. Exploring stereochemical complexity and developing extended D3R SAR from this new library complements previously described SAR and inspires future structural and computational biology investigation. Moreover, the expansion of chemical space characterization for D3R agonism may be utilized in machine learning and artificial intelligence (AI)-based drug design, in the future.

NITROGEN-CONTAINING CONDENSED RING COMPOUNDS HAVING DOPAMINE D3 ANTAGONISTIC EFFECT

Novel compounds having D3 receptor antagonistic activity are provided. A compound represented by formula (I): wherein ring A is a heterocycle, X1 is each independently CR4aR4b, X2 is each independently CR4c

Design, synthesis, and evaluation of potent and selective ligands for the dopamine 3 (D3) receptor with a novel in vivo behavioral profile

A series of compounds structurally related to pramipexole were designed, synthesized, and evaluated as ligands for the dopamine 3 (D3) receptor. Compound 12 has a Ki value of 0.41 nM to D3 and a selectivity of > 30000- and 800-fold over the D1-like and D 2 receptors, respectively. Our in vivo functional assays showed that this compound is a partial agonist at the D3 receptor with no detectable activity at the D2 receptor.