376348-78-6

Basic information

• Product Name: 4,4-DIFLUORO-N-((1S)-3-OXO-1-PHENYLPROPYL)CYCLOHEXANE-1-CARBOXAMIDE
• Synonyms: 4,4-DIFLUORO-N-((1S)-3-OXO-1-PHENYLPROPYL)CYCLOHEXANE-1-CARBOXAMIDE;Cyclohexanecarboxamide, 4,4- difluoro-N-[(1S)-3-oxo-1-[phenylpropyl]-;4,4-Difluoro-N-((1S)-3-oxo-1-phenylpropyl)cyclohexanecarboxamide;4,4-Difluorocyclohexanecarboxylic acid N-((1S)-3-oxo-1-phenylpropyl)amide
• CAS NO: 376348-78-6
• Molecular Formula: C₁₆H₁₉F₂NO₂
• Molecular Weight: 295.32
• Mol File: 376348-78-6.mol

Chemical Properties

• Appearance: /
• CAS DataBase Reference: 4,4-DIFLUORO-N-((1S)-3-OXO-1-PHENYLPROPYL)CYCLOHEXANE-1-CARBOXAMIDE(CAS DataBase Reference)
• NIST Chemistry Reference: 4,4-DIFLUORO-N-((1S)-3-OXO-1-PHENYLPROPYL)CYCLOHEXANE-1-CARBOXAMIDE(376348-78-6)
• EPA Substance Registry System: 4,4-DIFLUORO-N-((1S)-3-OXO-1-PHENYLPROPYL)CYCLOHEXANE-1-CARBOXAMIDE(376348-78-6)

Safety Data

• Hazardous Substances Data: 376348-78-6(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
4,4-Difluoro-N-((1S)-3-oxo-1-phenylpropyl)cyclohexane-1-carboxamide is used as a pharmaceutical intermediate for the development of various drugs. Its unique structure allows it to be a key component in the synthesis of different medicinal compounds.
Used in HIV Therapy:
In the field of HIV treatment, (S)-4,4-Difluoro-N-(3-oxo-1-phenylpropyl)cyclohexanecarboxamide acts as a reagent in the synthesis of CCR5 antagonists. These antagonists play a crucial role in blocking the CCR5 co-receptor, which is utilized by the HIV virus to enter human cells. This helps in preventing the virus from replicating and spreading within the body.
Used in Treatment of Graft-vs.-Host Disease:
4,4-DIFLUORO-N-((1S)-3-OXO-1-PHENYLPROPYL)CYCLOHEXANE-1-CARBOXAMIDE may also be relevant for the treatment of graft-vs.-host disease, a condition that occurs when donated immune cells attack the recipient's body after a bone marrow or stem cell transplant. The CCR5 antagonists synthesized using the compound can help in managing the immune response and reducing the severity of the disease.
Used in Treatment of Staphylococcus aureus Infection:
Additionally, 4,4-Difluoro-N-((1S)-3-oxo-1-phenylpropyl)cyclohexane-1-carboxamide may contribute to the development of treatments for Staphylococcus aureus infections. 4,4-DIFLUORO-N-((1S)-3-OXO-1-PHENYLPROPYL)CYCLOHEXANE-1-CARBOXAMIDE's role in synthesizing CCR5 antagonists can potentially help in targeting and combating the bacteria, which is known for its antibiotic resistance and ability to cause severe infections.

Upstream product

• 122665-97-8 4,4-difluorocyclohexanecarboxylic acid 
• 376348-77-5 (S)-4,4-difluoro-N-(3-hydroxy-1-phenylpropyl)cyclohexanecarboxamide 
• 376348-76-4 ethyl (S)-3-[(4,4-difluorocyclohexyl)carboxamido]-3-phenylpropanoate 
• 376348-75-3 4,4-difluorocyclohexane-1-carbonyl chloride 
• 340188-50-3 ethyl (S)-3-amino-3-phenyl-propionate hydrochloride 
• 1255215-12-3 (4,4-difluorocyclohexyl)((3S)-5-hydroxy-3-phenylisoxazolidin-2-yl)methanone 
• 1000681-06-0 4,4-difluoro-cyclohexanecarboxylic acid (1-phenyl-but-3-enyl)-amide 

Downstream Products

• 376348-65-1 maraviroc 
• 376348-77-5 (S)-4,4-difluoro-N-(3-hydroxy-1-phenylpropyl)cyclohexanecarboxamide 
• 1519003-77-0 C₃₆H₅₄F₂N₈O 
• 891823-49-7 4,4-difluoro-cyclohexanecarboxylic acid{(S)-3-[1,3-diethyl-bicyclo[3.2.1]-2,4-dioxo-1β,3,8-triaza-spiro[4.5]dodec-8-yl]-1-phenyl-propyl}-amide 
• 891823-46-4 4,4-difluoro-cyclohexanecarboxylic acid {(S)-3-[3-(4-methanesulfonyl-benzyl)-bicyclo[3.2.1]-2,4-dioxo-1α,3,8-triaza-spiro[4.5]dodec-8-yl]-1-phenyl-propyl}-amide 

Relevant articles and documents

Preparation method of

The preparation method comprises the following steps: taking a halogen-containing azide compound as a raw material in γ-position, carrying out a reaction, and preparing and a derivative thereof. The method is characterized in γ-position halogen-containing azide compound as a raw material and is subjected to reduction. A series of non-sequential reactions, such as hydrolysis, substitution, condensation, reductive amination, and the like. A target compound, that is, a Mahalanobis derivative, can be obtained. The preparation method has the advantages of mild reaction conditions, simplicity and convenience in operation, low cost, less side reaction, high product purity, simplicity and convenience in separation and purification and the like. The invention further provides the pulvernolol and derivatives thereof prepared by the method and application thereof.

METHOD FOR PREPARING MARAVIROC

Provided is a method for preparing a tropane derivative, maraviroc, including reacting a compound of formula (II) with a compound of formula (I), wherein the compound of formula (II) is prepared by the steps of acetylation of a compound of formula (III), activation and substitution of a compound of formula (IV) by a chlorination agent, cyclization of a compound of formula (V), and debenzylation of a compound of formula (VI) by hydrogenation. Hence, the present disclosure provides a method for preparing maraviroc with good yield and simple operation.

A PROCESS FOR THE SYNTHESIS OF MARAVIROC

A process for the synthesis of Maraviroc The invention relates to a new approach to synthesis of Maraviroc, a substance with the chemical name N-{(lS)-3-[3-(3-isopropy)-5- methyl-4 H-l,2,4-triazol-4-yl-exo-8-azabicyclo-[3.2.1]oct-8-yl]-l- phenylpropyl}-4,4-difluorocyclohexanecarboxamide and the structure of formula I using the borrowing hydrogen method also called hydrogen autotransfer method as well as improved isolation and purification of the final product.

Asymmetric synthesis of maraviroc (UK-427,857)

The asymmetric synthesis of Maraviroc (UK-427,857), a chemochine receptor 5 (CCR-5) receptor antagonist, based on an expeditious organocatalytic enantioselective assembly of the chiral βamino aldehyde key fragment is presented. The reactions were performed on a gram-scale and allow for the rapid construction of new Maraviroc analogues.

Process research and scale-up of a commercialisable route to maraviroc (UK-427,857), a CCR-5 receptor antagonist

A six-step synthetic route to the CCR-5 receptor antagonist, Maraviroc (UK-427,857) (1) has been developed and demonstrated at scale in a pilot plant. The route has supported four Pilot-Plant campaigns and has produced multikilogram quantities of 1. Continued development of the synthetic route has resulted in a robust process with improved throughput compared to that of the original synthesis (Haycock-Lewandowski, S. J.; Mawby, N. J.; Wilder, A.; Ahman, J. Org. Process Res. Dev. 2008, 12, 1094-1103).

Asymmetric allylboration of acyl imines catalyzed by chiral diols

Chiral BINOL-derived diols catalyze the enantioselective asymmetric allylboration of acyl imines. The reaction requires 15 mol % (S)-3,3′-Ph2-BINOL as the catalyst and allyldiisopropoxyborane as the nucleophile. The reaction products are obtained in good yields (75-94%) and high enantiomeric ratios (95:5-99.5:0.5) for aromatic and aliphatic imines. High diastereoselectivities (diastereomeric ratio > 98:2) and enantioselectivities (enantiomeric ratio > 98:2) are obtained in the reactions of acyl imines with crotyldiisopropoxyboranes. This asymmetric transformation is directly applied to the synthesis of Maraviroc, the selective CCR5 antagonist with potent activity against HIV-1 infection. Mechanistic investigations of the allylboration reaction including IR, NMR, and mass spectrometry studies indicate that acyclic boronates are activated by chiral diols via exchange of one of the boronate alkoxy groups with activation of the acyl imine via hydrogen bonding.