(1R,2R)-1-Amino-2-(difluoromethyl)-N-[(1-methylcyclopropyl)sulfonyl]cyclopropanecarboxamide hydrochloride (1:1)
[CAS# 1360828-80-3]

Identification

• Classification: Organic raw materials >> Amino compound >> Amide compound
• Name: (1R,2R)-1-Amino-2-(difluoromethyl)-N-[(1-methylcyclopropyl)sulfonyl]cyclopropanecarboxamide hydrochloride (1:1)
• Synonyms: (1R)-1-amino-2-(difluoromethyl)-N-(1-methylcyclopropyl)sulfonylcyclopropane-1-carboxamide;hydrochloride
• Molecular Formula: C₉H₁₄F₂N₂O₃S^.HCl
• Molecular Weight: 304.74
• CAS Registry Number: 1360828-80-3
• EC Number: 943-460-6
• SMILES: CC1(CC1)S(=O)(=O)NC(=O)[C@]2(CC2C(F)F)N.Cl

Safety Data

• Hazard Symbols: GHS05 Danger
• Hazard Statements: H318
• Precautionary Statements: P264+P265-P280-P305+P354+P338-P317

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Serious eye damage	Eye Dam.	1	H318

Discovory and Applicatios

(1R,2R)-1-Amino-2-(difluoromethyl)-N-[(1-methylcyclopropyl)sulfonyl]cyclopropanecarboxamide hydrochloride (1:1) is a synthetic small molecule that belongs to a class of difluoromethylated cyclopropane carboxamides developed for pharmaceutical research. Structurally, it contains a cyclopropane core with two chiral centers in the 1R,2R configuration, an amino substituent, a difluoromethyl group, and a sulfonamide moiety attached to a 1-methylcyclopropyl group. The compound is typically isolated as a hydrochloride salt to improve solubility and stability. It has attracted attention as a structural motif in medicinal chemistry due to the combination of conformational rigidity provided by the cyclopropane ring and the unique electronic and lipophilic properties of the difluoromethyl group.

The discovery of this compound type is linked to studies on fluorinated analogues of amino acid derivatives and sulfonamide-containing bioactive molecules. Fluorine incorporation, particularly in the form of difluoromethyl substituents, can enhance metabolic stability and bioavailability while maintaining hydrogen-bonding capacity similar to that of hydroxyl groups. In the context of drug discovery, such structural modifications often lead to improvements in pharmacokinetic profiles, enzyme selectivity, or receptor binding affinity. The cyclopropane framework serves as a conformationally restricted scaffold that mimics the geometry of peptide bonds or small cyclic amino acid residues, making this class of compounds valuable in the design of enzyme inhibitors and receptor agonists.

In recent pharmaceutical research, (1R,2R)-1-amino-2-(difluoromethyl)-N-[(1-methylcyclopropyl)sulfonyl]cyclopropanecarboxamide hydrochloride has been explored as a key intermediate or lead structure in the development of antiviral agents and metabolic modulators. Its difluoromethylated amino acid–like backbone has inspired the synthesis of analogues targeting proteases and other enzymes involved in viral replication. The compound’s hydrochloride form facilitates handling in laboratory settings and enhances compatibility with aqueous reaction systems, which is beneficial for subsequent coupling reactions or biological testing.

Synthetic approaches for producing this compound typically involve the stepwise introduction of the difluoromethyl group and sulfonamide functionality onto a preformed chiral cyclopropane core. Enantioselective cyclopropanation or asymmetric synthesis from chiral precursors allows precise control over the (1R,2R) stereochemistry. The sulfonylation step, usually performed under mild conditions, introduces the (1-methylcyclopropyl)sulfonyl substituent, which confers additional hydrophobic character and steric bulk that can modulate the compound’s biological interactions. The final hydrochloride salt is obtained through acid treatment, providing a crystalline, stable form suitable for formulation or storage.

Applications of this compound and its analogues continue to expand within medicinal chemistry, particularly in the search for novel therapeutic agents that exploit fluorinated small molecules for improved efficacy and safety. Its distinctive combination of fluorinated and cyclopropyl groups has made it a valuable scaffold in the optimization of lead compounds where fine-tuning of molecular conformation and lipophilicity is essential. Research involving this molecule demonstrates the importance of integrating fluorine chemistry and chiral synthesis in the rational design of next-generation pharmaceuticals.

References

Zhang Y, Li X, Chen J, et al. (2025) Discovery and optimization of novel indolecarboxylic acid derivative as potent glucagon-like peptide-1 receptor agonists. Molecular Diversity. DOI: 10.1007/s11030-025-11213-7

Maas R, De Vries H, Smit M, et al. (2022) Synthesis of Danuglipron: An orally available GLP-1R agonist. Synfacts. DOI: 10.1055/s-0041-1738304

Meanwell NA (2018) Fluorine and fluorinated motifs in the design and application of bioisosteres for drug design. Journal of Medicinal Chemistry 61(14) 5822–5880. DOI: 10.1021/acs.jmedchem.7b01788