1156491-10-9 | (1R trans)-2-(3,4-difluorophenyl)cyclopropane amine

CAS:1156491-10-9 | (1R trans)-2-(3,4-difluorophenyl)cyclopropane amine,Description

“(1R,2S)-2-(3,4-difluorophenyl)cyclopropanamine hydrochloride” is an impurity of Ticagrelor, a reversible P2Y12 receptor antagonist used for the prevention of stroke, heart attack, and other events in people with acute coronary syndrome.

Synthesis Analysis

The synthesis of “(1R,2S)-2-(3,4-difluorophenyl)cyclopropanamine hydrochloride” involves several steps. The compound of formula V can be obtained from the compound of formula IV by cyclopropanization reaction. The compound of formula II is converted into acid amides, followed by Hofmann degradation, then type I compound is obtained into salt with D mandelic acids. Another method involves adding 4 mL of 37% HCI to a solution of Villa’ (0.30 g, 1.12 mmol) in MeOH (10 mL). The resulting reaction mixture is stirred at 25 C for 2 h, then MeOH is partly evaporated, water (10 mL) is added, white precipitate is filtered off, washed with water (5 mL), and dried to afford the title compound CPA as HCI salt (0.18 g, 76% yield).

Molecular Structure Analysis

The molecular formula of “(1R,2S)-2-(3,4-difluorophenyl)cyclopropanamine” is C9H9F2N. It has an average mass of 169.171 Da and a monoisotopic mass of 169.070313 Da.

Chemical Reactions Analysis

The compound undergoes a series of reactions including cyclopropanization, Hofmann degradation, and salt formation with D mandelic acids to yield the desired product.

Physical And Chemical Properties Analysis

The compound has a density of 1.3±0.1 g/cm3, a boiling point of 212.5±40.0 °C at 760 mmHg, and a vapour pressure of 0.2±0.4 mmHg at 25°C. It has an enthalpy of vaporization of 44.9±3.0 kJ/mol and a flash point of 99.0±14.4 °C. It is a solid substance that is white to off-white in color. It is slightly soluble in DMSO and methanol when sonicated.

Scientific Research Applications

• Synthesis of Ticagrelor : This compound is a crucial intermediate in the synthesis of Ticagrelor. Studies have focused on optimizing the synthesis process using different techniques. For instance, Pan Xian-hua (2013) explored the Corey-Chaykovsky asymmetric cyclopropanation reactions to improve the yield and purity of this compound in the context of Ticagrelor synthesis (Pan Xian-hua, 2013).
• Enzymatic Processes : Research by Guo et al. (2017) developed an enzymatic process for preparing a related chiral intermediate, which is significant for Ticagrelor synthesis. This process emphasizes green and environmentally sound methodologies with high productivity (Guo et al., 2017).
• Biocatalytic Synthesis : Hernandez et al. (2016) conducted studies on biocatalytic synthesis, emphasizing the potential of enzyme-catalyzed processes to replace multi-step chemical syntheses for pharmaceutical intermediates like this compound (Hernandez et al., 2016).
• Hydrolytic Resolution for Ticagrelor Synthesis : Wang et al. (2019) explored hydrolytic resolution processes in the preparation of this compound, highlighting improvements in enzyme activity and enantioselectivity (Wang et al., 2019).
• Other Pharmacological Applications : Research extends to other pharmacological applications as well, such as the study by Blass (2016) on cyclopropanamine compounds for treating conditions like schizophrenia and Alzheimer’s disease (Blass, 2016).

Safety And Hazards

The compound is harmful if swallowed and causes skin and eye irritation. It may also cause respiratory irritation. It is recommended to avoid breathing mist, gas, or vapours and to avoid contact with skin and eyes. Use personal protective equipment and ensure adequate ventilation. Remove all sources of ignition and evacuate personnel to safe areas.

Future Directions

“(1R,2S)-2-(3,4-difluorophenyl)cyclopropanamine hydrochloride” is a key intermediate in the synthesis of Ticagrelor, a drug used for the prevention of stroke, heart attack, and other events in people with acute coronary syndrome. As such, it is likely to continue to be of interest in pharmaceutical research and development.

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