processo para a preparação de bortezomib, composto, bortezomib ou seu anidrido, e, processo para a preparação de um composto

• Main Authors: Ravikumar H. Puppala, Srinivas Laxminarayan Pathi, RAJENDRA NARAYANRAO KANKAN, DHARMARAJ RAMACHANDRA RAO
• Format: Patent
• Language: Portuguese
• Published: 04.07.2017
• Subjects: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAININGELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN,SULFUR, SELENIUM OR TELLURIUM; CHEMISTRY; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY

1 / 2 resumo “processo para a preparaã‡ãƒo de bortezomib, composto, bortezomib ou seu anidrido, e, processo para a h c preparaã‡ãƒo de um composto†3 ch 3 a presente invenã§o ã£o fornece prc oce h ssos melhorados para a ch 3 3 h o o n preparaã§ã£o de bortezomib, terc-butil[1-({(1s)-3-metil-1-[(3as,4s,6s,7as)- ch n b 3 h o 3a,5,5-trimetilexaidro-4,6-metano-1,3,2-benzodioxaborol-2-il]butil}amino)-1- o oxo-3-fenilpropan-2-il]carbamato da fã³rmula (iv) (iv) e n-{(1s)-3-metil-1-[(3as,4s,6s,7as)-3a,5,5-trimetilexaidro-4,6-metano- 1,3,2-benzodioxaborol-2-il]butil} fenilalanina da fã³rmula (v) h c 3 ch 3 o ch ch 3 3 o h n 2 n b ch 3 h o (v) . o composto (iv) ã© preparado acoplando (1r)-3-metil-1-[(3as,4s,6s,7ar)- 3a,5,5-trimetil-hexaidro-4,6-metano-1,3,2-benzodioxaborol-2-il]butan-1- amina da fã³rmula (ii) h c 3 ch ch 3 ch 3 3 o b ch 3 o h n 2 (ii) ou seu sal com n-(terc-butoxicarbonil)-l-fenilalanina da fã³rmula (iii) 2 / 2 o h o n oh o (iii) em um primeiro solvente na presenã§a de um primeiro agente de acoplamento e uma primeira base, em que o processo de acoplamento nã£o compreende troca de solvente. o composto (v) ã© preparado desprotegendo o composto (iv) usando uma soluã§ã£o alcoã³lica de um ã¡cido inorgã¢nico. 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.