205393-22-2

Basic information

• Product Name: BORTEZOMIB-PINANEDIOL
• Synonyms: BORTEZOMIB-PINANEDIOL;Bortezomib pinanediol ester;N-[(1S)-2-[[(1R)-1-[(3aS,4S,6S,7aR)-Hexahydro-3a,5,5-trimethyl-4,6-methano-1,3,2-benzodioxaborol-2-yl]-3-methylbutyl]amino]-2-oxo-1-(phenylmethyl)ethyl]-2-pyrazinecarboxamide;Bortezomib intermediates III;(1S,2S,3R,5S)-Pinanediol N-(2-pyrazinecarbony1)-L-phenylalanine-L-leucine boronate;BortezoMib InterMediate III (BortezoMib pinanediol ester);BortezoMib VI;BortezoMib interMediates N-1
• CAS NO: 205393-22-2
• Molecular Formula: C₂₉H₃₉BN₄O₄
• Molecular Weight: 518.462
• EINECS: 1806241-263-5
• Product Categories: Boron Derivatives;Chiral Reagents;Intermediates
• Mol File: 205393-22-2.mol
• Article Data: 13

Chemical Properties

• Melting Point: 75-83°C
• Boiling Point: 719.5±60.0 °C(Predicted)
• Appearance: Yellow solid
• Density: 1.19
• Storage Temp.: -20?C Freezer
• Solubility: Chloroform, DMSO (Slightly), Ethanol, Ethyl Acetate, Methanol (Slightly)
• PKA: 11.97±0.46(Predicted)
• CAS DataBase Reference: BORTEZOMIB-PINANEDIOL(CAS DataBase Reference)
• NIST Chemistry Reference: BORTEZOMIB-PINANEDIOL(205393-22-2)
• EPA Substance Registry System: BORTEZOMIB-PINANEDIOL(205393-22-2)

Safety Data

• Hazardous Substances Data: 205393-22-2(Hazardous Substances Data)

Usage

Chemical Properties

Yellow Solid

Uses

Intermediate in the preparation of Bortezomib (B675700), a dipeptidyl boronate proteasome inhibitor.

Upstream product

• 98-97-5 2-pyrazylcarboxylic acid 
• 1310383-72-2 (aR,3aS,4S,6S,7aR)-hexahydro-3a,8,8-trimethyl-α-(2-methylpropyl)-4,6-methano-1,3,2-benzodioxaborole-2-methanamine 2,2,2-trifluoroacetate 
• 18680-27-8 pinanediol 
• 85167-14-2 (3aS,4S,6S,7aR)-2-[(1S)-1-chloro-3-methylbutyl]-3a,5,5-trimethylhexahydro-4,6-methano-1,3,2-benzodioxaborole 
• 84110-34-9 2-(2-methylpropyl)-(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methano-1,3,2-benzodioxaborole 
• 1310383-72-2 (1R)-3-methyl-1-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-4,6-methano-1,3,2-benzodioxaborole-2-yl]butan-1-amine trifluoroacetatic acid salt 
• 779357-85-6 (1R)-1-[(3aS,4S,6S,7aR)-hexahydro-3a,5,5-trimethyl-4,6-methano-1,3,2-benzodioxaborol-2-yl]-3-methylbutylamine hydrochloride 
• 114457-94-2 (S)-3-phenyl-2[(pyrazine-2-carbonyl)-amino]propionic acid 
• 19847-10-0 pyrazinoyl chloride 
• 789472-91-9 N-{(1S)-3-methyl-1-[(3aS,4S,6S,7aS)-3a,5,5-trimethylhexahydro-4,6-methano-1,3,2-benzodioxaborol-2-yl]butyl}phenylalanine amide 
• 779357-85-6 (1R)-3-methyl-1-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-4,6-methano-1,3,2-benzodioxabor-ol-2-yl]butan-1-amine hydrochloride 
• 7524-50-7 methyl (2S)-2-amino-3-phenylpropanoate hydrochloride 
• 179324-86-8 (1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0^2,6]decan-4-yl]butan-1-amine 
• 73058-37-4 N-(2-pyrazinylcarbonyl)-L-phenylalanine methyl ester 

Downstream Products

• 390800-88-1 bortezomib 
• 179324-69-7 velcade 

Relevant articles and documents

Discovery of Novel Peptidomimetic Boronate ClpP Inhibitors with Noncanonical Enzyme Mechanism as Potent Virulence Blockers in Vitro and in Vivo

Caseinolytic protease P (ClpP) is considered as a promising target for the treatment of Staphylococcus aureus infections. In an unbiased screen of 2632 molecules, a peptidomimetic boronate, MLN9708, was found to be a potent suppressor of SaClpP function. A time-saving and cost-efficient strategy integrating in silico position scanning, multistep miniaturized synthesis, and bioactivity testing was deployed for optimization of this hit compound and led to fast exploration of structure-activity relationships. Five of 150 compounds from the miniaturized synthesis exhibited improved inhibitory activity. Compound 43Hf was the most active inhibitor and showed reversible covalent binding to SaClpP while did not destabilize the tetradecameric structure of SaClpP. The crystal structure of 43Hf-SaClpP complex provided mechanistic insight into the covalent binding mode of peptidomimetic boronate and SaClpP. Furthermore, 43Hf could bind endogenous ClpP in S. aureus cells and exhibited significant efficacy in attenuating S. aureus virulence in vitro and in vivo.

AN IMPROVED PROCESS FOR THE PREPARATION OF BORONIC ACID ESTERS

The present invention relates to an improved process for the preparation of a compound of formula (I), wherein PG1 may be independently selected from tert-butyloxycarbonyl (Boc), phthaloyl, 9-fluorenylmethyloxycarbonyl (Fmoc), triphenylmethyl (Trityl), carboxybenzyl (Cbz), trifluoroacetyl, benzyl (Bn), benzylidene, methanesulfonyl (Mesyl), toluene sulfonyl (Tosyl) or acyl; its isolation as solid and use for the preparation of the compound of formula (IV), in particular the compound of formula (IV) i.e. [(1R)-3-methyl-1[[(2S)-1-oxo-3-phenyl-2- [(pyrazinylcarbonyl) amino]propyl]amino]butyl] boronic acid with more than 99.95% chiral purity, as measured by HPLC.

PROCESS FOR PREPARING OF BORTEZAMIB

The present invention provides improved processes for the preparation of Bortezomib, tert-butyl[1-({(1S)-3-methyl-1-[(3aS,4S,6S,7aS)-3a,5,5-trimethylhexahydro-4,6-methano-1,3,2-benzodioxaborol-2-yl]butyl}amino)-1-oxo-3-phenylpropan-2-yl]carbamate of formula (IV) and N-{(1S)-3-methyl-1-[(3aS,4S,6S,7aS)-3a,5,5-trimethylhexahydro-4,6- methano-1,3,2-benzodioxaborol-2-yl]butyl} phenylalanine of formula (V). Compound (IV) is prepared by coupling (1R)-3-methyl-1-[(3aS,4S,6S,7aR)-3a,5,5-trimethyl- hexahydro-4,6-methano-1,3,2-benzodioxaborol-2-yl]butan-1-amine of formula (II) or its salt with N-(tert-butoxycarbonyl)-L-phenylalanine of formula (III) in a first solvent in the presence of a first coupling agent and a first base, wherein the coupling process does not comprise solvent exchange. Compound (V) is prepared by deprotecting compound (IV) using an alcoholic solution of an inorganic acid.