133645-51-9

Basic information

• Product Name: (4R,5S,2'R,3'R,2S)-3-[3'-(N-tert-butoxycarbonyl-2-pyrrolidinyl)-3-hydroxy-2'-methylpropanoyl]-4-methyl-5-phenyl-2-oxazolidinone
• Synonyms: (4R,5S,2'R,3'R,2S)-3-[3'-(N-tert-butoxycarbonyl-2-pyrrolidinyl)-3-hydroxy-2'-methylpropanoyl]-4-methyl-5-phenyl-2-oxazolidinone
• CAS NO: 133645-51-9
• Molecular Weight: 432.517
• Mol File: 133645-51-9.mol
• Article Data: 22

Chemical Properties

• CAS DataBase Reference: (4R,5S,2'R,3'R,2S)-3-[3'-(N-tert-butoxycarbonyl-2-pyrrolidinyl)-3-hydroxy-2'-methylpropanoyl]-4-methyl-5-phenyl-2-oxazolidinone(CAS DataBase Reference)
• NIST Chemistry Reference: (4R,5S,2'R,3'R,2S)-3-[3'-(N-tert-butoxycarbonyl-2-pyrrolidinyl)-3-hydroxy-2'-methylpropanoyl]-4-methyl-5-phenyl-2-oxazolidinone(133645-51-9)
• EPA Substance Registry System: (4R,5S,2'R,3'R,2S)-3-[3'-(N-tert-butoxycarbonyl-2-pyrrolidinyl)-3-hydroxy-2'-methylpropanoyl]-4-methyl-5-phenyl-2-oxazolidinone(133645-51-9)

Safety Data

• Hazardous Substances Data: 133645-51-9(Hazardous Substances Data)

Upstream product

• 69610-41-9 Boc-L-Pro-H 
• 37577-28-9 (1S,2R)-(+)-norphedrine 
• 77943-39-6 4-methyl-5-phenyloxazolidin-2-one 
• 77877-20-4 (4R,5S)-4-methyl-5-phenyl-3-propionyloxazolidin-2-one 
• 59378-81-3 1-(tert-butoxycarbonyl)prolin-2R-ol 
• 73365-02-3 tert-butoxycarbonyl-D-prolinal 
• 54418-69-8 4-methyl-5-phenyl-2-oxazolidinone 
• 69610-40-8 N-(tert-butoxycarbonyl)-L-prolinol 
• 15761-39-4 1-(tert-butoxycarbonyl)-L-proline 

Downstream Products

• 77943-39-6 4-methyl-5-phenyloxazolidin-2-one 
• 133565-40-9 <1R-(1α,2β,7aα)>-Hexahydro-1-hydroxy-2-methyl-3-oxo-1H-pyrrolizine 
• 159173-45-2 (3R,4S,5S)-Dil-(2R,3R,4S)-Dap-(S)-Doe 
• 110417-88-4 dolastatin 10 
• 148597-90-4 Boc-(3R,4S,5S)-Dil-(2R,3R,4S)-Dap-(S)-Doe 
• 148565-06-4 Boc-(2R,3R,4S)-norDap-(S)-Doe 
• 148683-12-9 Boc-(3R,4S,5S)-bisnorDil-(2R,3R,4S)-norDap-(S)-Doe 
• 160800-65-7 tert-butyl (2S)-2-[(1R,2R)-3-{[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidine-1-carboxylate 
• 160800-83-9 (2R,3R)-N-[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]-3-methoxy-2-methyl-3-[(2S)-pyrrolidin-2-yl]propanamide, trifluoroacetic acid salt 
• 161485-82-1 tert-butyl (S)-2-((1R,2R)-1-methoxy-3-(((S)-1-methoxy-1-oxo-3-phenylpropan-2-yl)amino)-2-methyl-3-oxopropyl)pyrrolidine-1-carboxylate 
• 161485-88-7 methyl (S)-2-((2R,3R)-3-methoxy-2-methyl-3-((S)-pyrrolidin-2-yl)propanamido)-3-phenylpropanoate 2,2,2-trifluoroacetate 
• 1438852-21-1 methyl (S)-2-((2R,3R)-3-((S)-1-((3R,4S,5S)-4-((S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-N,3-dimethylbutanamido)-3-methoxy-5-methylheptanoyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanamido)-3-phenylpropanoate 

Relevant articles and documents

Process Development and GMP Production of a Conjugate Warhead: Auristatin F-HPA-Ala/TFA (XMT-1864/TFA)

An efficient, large-scale manufacturing process is described for XMT-1864/TFA (1-TFA), an auristatin F derivative, used as a novel, highly potent, cytotoxic warhead in Mersana's oncology antibody-drug conjugate platforms. The process achieves high diastereomeric purity and controls the impurities with all intermediates readily isolated by crystallization or precipitation in high yield and purity. Protecting groups were selected to ensure tolerability, scalability, and stability of the intermediates under various solution-phase peptide coupling conditions. Crystallization of the final product was developed to remove specified impurities and provide a high-purity active warhead molecule for use in the bioconjugation processing. The convergent synthesis involving six non-GMP steps and five GMP steps has been carried out in multiple cGMP productions on 1-kg scale to produce 1-TFA in >98% chemical purity and 1% total diastereomeric contamination with ～50% overall yield for the GMP steps.

EFFICIENT PREPARATION OF DOLASTATIN AND AURISTATIN ANALOGS THROUGH A COMMON INTERMEDIATE

Methods for making a dolastatin, auristatin or related compounds comprising the steps of providing a universal dolastatin core of Formula (I) reacting the C-terminal carboxylic acid group with an amine (A) to form an amide bond and reacting the N-terminal amine with a carboxylic acid (CA) to form an amide bond, wherein the steps can be performed in either order. Also provided are an isolated salt of the universal dolastatin core for use in preparation of dolastatins, auristatins and related compounds. Also provided are a number of intermediates and process steps which are useful for the preparation of high purity dolastatin core and high purity dolastatin and auristatin compounds.

CONJUGATION OF A CYTOTOXIC DRUG WITH BIS-LINKAGE

What provided is the conjugation of cytotoxic to a cell-binding molecule with a bis-linker(dual-linker) as shown in Formula (I). It provides bis-linkage methods of making a conjugate of a cytotoxic drug molecule to a cell-binding agent in a specific manner. It also relates to application of the conjugates for the treatment of a cancer, or an autoimmune disease, or an infectious disease.