1353891-90-3

Basic information

• Product Name: tert-butyl (1R,2S)-1,2-bis(4-chlorophenyl)-2-(2-isopropoxy-4-methoxybenzamido)ethylcarbamate
• Synonyms: tert-butyl (1R,2S)-1,2-bis(4-chlorophenyl)-2-(2-isopropoxy-4-methoxybenzamido)ethylcarbamate
• CAS NO: 1353891-90-3
• Molecular Weight: 573.516
• Mol File: 1353891-90-3.mol
• Article Data: 4

Chemical Properties

• CAS DataBase Reference: tert-butyl (1R,2S)-1,2-bis(4-chlorophenyl)-2-(2-isopropoxy-4-methoxybenzamido)ethylcarbamate(CAS DataBase Reference)
• NIST Chemistry Reference: tert-butyl (1R,2S)-1,2-bis(4-chlorophenyl)-2-(2-isopropoxy-4-methoxybenzamido)ethylcarbamate(1353891-90-3)
• EPA Substance Registry System: tert-butyl (1R,2S)-1,2-bis(4-chlorophenyl)-2-(2-isopropoxy-4-methoxybenzamido)ethylcarbamate(1353891-90-3)

Safety Data

• Hazardous Substances Data: 1353891-90-3(Hazardous Substances Data)

Upstream product

• 86212-34-2 (1R,2S)-1,2-bis(4-chlorophenyl)ethane-1,2-diamine 
• 3848-36-0 4-chlorobenzaldoxime 
• 774225-25-1 N-(tert-butoxycarbonyl)-α-(phenylsulfonyl)-4-chlorobenzylamine 
• 4248-19-5 tert-butyl carbazate 
• 104-88-1 4-chlorobenzaldehyde 
• 106-43-4 para-chlorotoluene 
• 1353891-52-7 tert-butyl ((1R,2S)-1,2-bis(4-chlorophenyl)-2-nitroethyl)carbamate 
• 1353891-88-9 tert-butyl ((1R,2S)-2-amino-1,2-bis(4-chlorophenyl)ethyl)carbamate 
• 1353891-99-2 isopropyl 2-isopropoxy-4-methoxybenzoate 
• 779342-75-5 tert-butyl 4-chlorobenzylidenecarbamate 
• 29559-24-8 4-chlorophenylnitromethane 
• 622-95-7 4-chlorobenzyl bromide 
• 2237-36-7 4-methoxysalicylic acid 

Downstream Products

• 548472-68-0 nutlin-3a 
• 1353891-92-5 N-((1S,2R)-2-amino-1,2-bis(4-chlorophenyl)ethyl)-2-isopropoxy-4-methoxybenzamide 
• 1353891-93-6 N-((1R,2S)-1,2-bis(4-chlorophenyl)-2-(2-isopropoxy-4-methoxybenzamido)ethyl)-3-oxopiperazine-1-carboxamide 

Relevant articles and documents

Preparation of (-)-nutlin-3 using enantioselective organocatalysis at decagram scale

Chiral nonracemic cis-4,5-bis(aryl)imidazolines have emerged as a powerful platform for the development of cancer chemotherapeutics, stimulated by the Hoffmann-La Roche discovery that Nutlin-3 can restore apoptosis in cells with wild-type p53. The lack of efficient methods for the enantioselective synthesis of cis-imidazolines, however, has limited their more general use. Our disclosure of the first enantioselective synthesis of (-)-Nutlin-3 provided a basis to prepare larger amounts of this tool used widely in cancer biology. Key to the decagram-scale synthesis described here was the discovery of a novel bis(amidine) organocatalyst that provides high enantioselectivity at warmer reaction temperature (-20 C) and low catalyst loadings. Further refinements to the procedure led to the synthesis of (-)-Nutlin-3 in a 17 g batch and elimination of all but three chromatographic purifications.

Organocatalytic, diastereo- and enantioselective synthesis of nonsymmetric cis -stilbene diamines: A platform for the preparation of single-enantiomer cis -imidazolines for protein-protein inhibition

The finding by scientists at Hoffmann-La Roche that cis-imidazolines could disrupt the protein-protein interaction between p53 and MDM2, thereby inducing apoptosis in cancer cells, raised considerable interest in this scaffold over the past decade. Initial routes to these small molecules (i.e., Nutlin-3) provided only the racemic form, with enantiomers being enriched by chromatographic separation using high-pressure liquid chromatography (HPLC) and a chiral stationary phase. Reported here is the first application of an enantioselective aza-Henry approach to nonsymmetric cis-stilbene diamines and cis-imidazolines. Two novel mono(amidine) organocatalysts (MAM) were discovered to provide high levels of enantioselection (>95% ee) across a broad range of substrate combinations. Furthermore, the versatility of the aza-Henry strategy for preparing nonsymmetric cis-imidazolines is illustrated by a comparison of the roles of aryl nitromethane and aryl aldimine in the key step, which revealed unique substrate electronic effects providing direction for aza-Henry substrate-catalyst matching. This method was used to prepare highly substituted cis-4,5-diaryl imidazolines that project unique aromatic rings, and these were evaluated for MDM2-p53 inhibition in a fluorescence polarization assay. The diversification of access to cis-stilbene diamine-derived imidazolines provided by this platform should streamline their further development as chemical tools for disrupting protein-protein interactions.