Process for preparing atazanavir bisulfate and novel forms

A process is provided for preparing the HIV protease inhibitor atazanavir bisulfate wherein a solution of atazanavir free base is reacted with concentrated sulfuric acid in an amount to react with less than about 15% by weight of the free base, seeds of Form A crystals of atazanavir bisulfate are ad...

Full description

Saved in:
Bibliographic Details
Main Authors Kim, Soojin, Lotz, Bruce T, Malley, Mary F, Gougoutas, Jack Z, Davidovich, Martha, Srivastava, Sushil K
Format Patent
LanguageEnglish
Published 23.11.2010
Online AccessGet full text

Cover

Abstract A process is provided for preparing the HIV protease inhibitor atazanavir bisulfate wherein a solution of atazanavir free base is reacted with concentrated sulfuric acid in an amount to react with less than about 15% by weight of the free base, seeds of Form A crystals of atazanavir bisulfate are added to the reaction mixture, and as crystals of the bisulfate form, additional concentrated sulfuric acid is added in multiple stages at increasing rates according to a cubic equation, to effect formation of Form A crystals of atazanavir bisulfate.A process is also provided for preparing atazanavir bisulfate as Pattern C material. A novel form of atazanavir bisulfate is also provided which is Form E3 which is a highly crystalline triethanolate solvate of the bisulfate salt from ethanol.
AbstractList A process is provided for preparing the HIV protease inhibitor atazanavir bisulfate wherein a solution of atazanavir free base is reacted with concentrated sulfuric acid in an amount to react with less than about 15% by weight of the free base, seeds of Form A crystals of atazanavir bisulfate are added to the reaction mixture, and as crystals of the bisulfate form, additional concentrated sulfuric acid is added in multiple stages at increasing rates according to a cubic equation, to effect formation of Form A crystals of atazanavir bisulfate.A process is also provided for preparing atazanavir bisulfate as Pattern C material. A novel form of atazanavir bisulfate is also provided which is Form E3 which is a highly crystalline triethanolate solvate of the bisulfate salt from ethanol.
Author Srivastava, Sushil K
Lotz, Bruce T
Malley, Mary F
Gougoutas, Jack Z
Davidovich, Martha
Kim, Soojin
Author_xml – sequence: 1
  givenname: Soojin
  surname: Kim
  fullname: Kim, Soojin
– sequence: 2
  givenname: Bruce T
  surname: Lotz
  fullname: Lotz, Bruce T
– sequence: 3
  givenname: Mary F
  surname: Malley
  fullname: Malley, Mary F
– sequence: 4
  givenname: Jack Z
  surname: Gougoutas
  fullname: Gougoutas, Jack Z
– sequence: 5
  givenname: Martha
  surname: Davidovich
  fullname: Davidovich, Martha
– sequence: 6
  givenname: Sushil K
  surname: Srivastava
  fullname: Srivastava, Sushil K
BookMark eNrjYmDJy89L5WSwCijKT04tLlZIyy9SKChKLUgsysxLV0gsSaxKzEssyyxSSMosLs1JSyxJVUjMS1HIyy9LzQEpzi3mYWBNS8wpTuWF0twMCm6uIc4euqXFBUDleSXF8elFiSDKwNzC2MIMSBChBAB2uDIn
ContentType Patent
CorporateAuthor Bristol-Myers Squibb Company
CorporateAuthor_xml – name: Bristol-Myers Squibb Company
DBID EFH
DatabaseName USPTO Issued Patents
DatabaseTitleList
Database_xml – sequence: 1
  dbid: EFH
  name: USPTO Issued Patents
  url: http://www.uspto.gov/patft/index.html
  sourceTypes: Open Access Repository
DeliveryMethod fulltext_linktorsrc
ExternalDocumentID 07838678
GroupedDBID EFH
ID FETCH-uspatents_grants_078386783
IEDL.DBID EFH
IngestDate Sun Mar 05 22:34:53 EST 2023
IsOpenAccess true
IsPeerReviewed false
IsScholarly false
Language English
LinkModel DirectLink
MergedId FETCHMERGED-uspatents_grants_078386783
OpenAccessLink https://image-ppubs.uspto.gov/dirsearch-public/print/downloadPdf/7838678
ParticipantIDs uspatents_grants_07838678
PatentNumber 7838678
PublicationCentury 2000
PublicationDate 20101123
PublicationDateYYYYMMDD 2010-11-23
PublicationDate_xml – month: 11
  year: 2010
  text: 20101123
  day: 23
PublicationDecade 2010
PublicationYear 2010
References Earl, W.L. et al., "Measurement of 13C Chemical Shifts in Solids", Journal of Magnetic Resonance, vol. 48, pp. 35-54 (1982).
U.S. Appl. No. 11/119,551, filed May 2, 2005, Kim et al.
Fässler et al. (5849911) 19981200
Malamas et al. (5541205) 19960700
Malamas, M.S. at al., "Azole Phenoxy Hydroxyureas as Selective and Orally Active inhibitors of 5-Lipoxygenase", J. Med. Chem., vol. 39, No. 1, pp. 237-245 (1996).
Xu, Z. et al., "Process Research and Development for an Efficient Synthesis of the HIV Protease Inhibitor BMS-232632", Organic Process Research & Development, vol. 6, No. 3, pp. 323-328 (2002).
Yin, S. et al., "Simulated PXRD Patterns in Studies of the Phase Composition and Thermal Behavior of Bulk Crystalline Solids", American Pharmaceutical Review, vol. 6, No. 2, pp. 80-85 (2003).
Cheng et al. (6727271) 20040400
Johannsson, G. et al., "Growth Hormone Treatment of Abdominally Obese Men Reduces Abdominal Fat Mass, Improves Glucose and Lipoprotein Metabolism, and Reduces Diastolic Blood Pressure", Journal of Clinical Endocrinology and Metabolism, vol. 82, No. 3, pp. 727-734 (1997).
Kim et al. (2005/0256314) 20051100
Nakagawa et al. (4022776) 19770500
Cappola (6753012) 20040600
Venit et al. (6670344) 20031200
(WO 02/085335) 20021000
Grossman et al. (3980637) 19760900
Yu et al. (6316438) 20011100
Desai et al. (2005/0214373) 20050900
Mullin, J.W. et al., "Programmed cooling of batch crystallizers", Chemical Engineering Science, vol. 26, pp. 369-377 (1971).
Grimmett et al. (6136345) 20001000
Cheng et al. (6653314) 20031100
Metz, G. et al., "Ramped-Amplitude Cross Polarization in Magic-Angle-Spinning NMR", Journal of Magnetic Resonance, Series A, vol. 110, pp. 219-227 (1994).
Bauer et al. (6086919) 20000700
Robl et al. (6395767) 20020500
Cheng et al. (6414002) 20020700
Rusowicz et al. (2005/0288343) 20051200
(1 186 293) 20020300
(1 243 266) 20020900
Jones, A.G. et al., "Programmed Cooling Crystallization of Potassium Sulphate Solutions", Chemical Engineering Science, vol. 29, pp. 105-118 (1974).
Goldstein, S.W. et al., "Hydroxyurea Derivatives as Hypoglycemic Agents", J, Med. Chem., vol. 36, No. 15, pp. 2238-2240 (1993).
Singh et al. (6087383) 20000700
Otwinowski, Z. et al., "Processing of X-Ray Diffraction Data Collected in Oscillation Mode", Macromolecular Crystallography, Part A, Methods in Enzymology, vol. 276, Academic Press, publ., Carter, Jr., C.W. et al., eds., pp. 307-326 (1997).
Desai et al. (2005/0266080) 20051200
Malamas et al. (5428048) 19950600
Zerbe (4800084) 19890100
(WO 01/52825) 20010700
Hoy et al. (5489436) 19960200
Abramowitz et al. (5158777) 19921000
MacLean (2002/0094992) 20020700
Yoon et al. (2004/0022855) 20040200
Badorc et al. (4847265) 19890700
References_xml – year: 20021000
  ident: WO 02/085335
– year: 19760900
  ident: 3980637
  contributor:
    fullname: Grossman et al.
– year: 20020500
  ident: 6395767
  contributor:
    fullname: Robl et al.
– year: 19890100
  ident: 4800084
  contributor:
    fullname: Zerbe
– year: 20051100
  ident: 2005/0256314
  contributor:
    fullname: Kim et al.
– year: 20010700
  ident: WO 01/52825
– year: 20001000
  ident: 6136345
  contributor:
    fullname: Grimmett et al.
– year: 20020700
  ident: 2002/0094992
  contributor:
    fullname: MacLean
– year: 19960700
  ident: 5541205
  contributor:
    fullname: Malamas et al.
– year: 20051200
  ident: 2005/0266080
  contributor:
    fullname: Desai et al.
– year: 19921000
  ident: 5158777
  contributor:
    fullname: Abramowitz et al.
– year: 20031100
  ident: 6653314
  contributor:
    fullname: Cheng et al.
– year: 19950600
  ident: 5428048
  contributor:
    fullname: Malamas et al.
– year: 20040400
  ident: 6727271
  contributor:
    fullname: Cheng et al.
– year: 20031200
  ident: 6670344
  contributor:
    fullname: Venit et al.
– year: 20020700
  ident: 6414002
  contributor:
    fullname: Cheng et al.
– year: 20020300
  ident: 1 186 293
– year: 20020900
  ident: 1 243 266
– year: 19960200
  ident: 5489436
  contributor:
    fullname: Hoy et al.
– year: 19890700
  ident: 4847265
  contributor:
    fullname: Badorc et al.
– year: 20000700
  ident: 6086919
  contributor:
    fullname: Bauer et al.
– year: 20051200
  ident: 2005/0288343
  contributor:
    fullname: Rusowicz et al.
– year: 19770500
  ident: 4022776
  contributor:
    fullname: Nakagawa et al.
– year: 20000700
  ident: 6087383
  contributor:
    fullname: Singh et al.
– year: 20011100
  ident: 6316438
  contributor:
    fullname: Yu et al.
– year: 20040600
  ident: 6753012
  contributor:
    fullname: Cappola
– year: 20050900
  ident: 2005/0214373
  contributor:
    fullname: Desai et al.
– year: 20040200
  ident: 2004/0022855
  contributor:
    fullname: Yoon et al.
– year: 19981200
  ident: 5849911
  contributor:
    fullname: Fässler et al.
Score 2.7947245
Snippet A process is provided for preparing the HIV protease inhibitor atazanavir bisulfate wherein a solution of atazanavir free base is reacted with concentrated...
SourceID uspatents
SourceType Open Access Repository
Title Process for preparing atazanavir bisulfate and novel forms
URI https://image-ppubs.uspto.gov/dirsearch-public/print/downloadPdf/7838678
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV1LSwMxEB7aImhPior1RQ5eo5t9dNNepcsiKD0o9FYSM1sK2-yyjwr-eifbUrzoNY_JkJB5kG--ADzEiDGKWHAjx5KHmf7kMsSYKyUUCmMoBnC1w69v4_QjfFlEix6kh1qYDV0jXpIu9WNbl03RgSvJvO8Onu_Inx1HoHXsA182L5SZm-wploEkw9uHvvQctGuWpEM4JhEUstmm_uU0klM4mnetZ9BDew7TPSafUZjIygrd9392xVSjvpVV23XF9Lpu84zmMErvmS22mLvBm_oCWDJ7f075YaHlqnIAlqW3Vyi4hAEl8ngFDPXEOLIYL9CafIKaULITRr7yMy29SOoRjP4Uc_1P3w2cdG_aQnA_uIVBU7V4R66y0ffdPvwA0kp1lQ
link.rule.ids 230,309,786,808,891,64394
linkProvider USPTO
linkToPdf http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV1LT8MwDLbGQDxOIEAbzxy4Bpq1XTOusKq8ph5A2q1KSDpN6tKqjyHx63G6aeIC1zwcK1H82Yr9BeAm0DrQLGBU8SGnXio_Kfd0QIVgQjOl0AewtcNvk2H04T1P_WkHok0tzAKvES1Ql-q2qYo6b5Mr0byvDp6uyJ8tR6Cx7ANfJsuFilV6F3CXo-Hdgm2LsZZFfxxGB7CHQtBpM3X1CzbCQ9iJ29Yj6GhzDPfrrHyCjiIpSm0_ADQzImrxLYxYzksi51WTpTiHYIBPTL7UmR28qE6AhOP3h4huFkpmpU1hSZy1Su4pdDGU1z0gWo6UpYtxXCkRFcQIwx3PH4hBKrnjc9mH_p9izv7pu4bd-DFMXp8mL-ew3z5wM0YH7gV067LRl4ibtbxqt-QHwMx4jw
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Apatent&rft.title=Process+for+preparing+atazanavir+bisulfate+and+novel+forms&rft.inventor=Kim%2C+Soojin&rft.inventor=Lotz%2C+Bruce+T&rft.inventor=Malley%2C+Mary+F&rft.inventor=Gougoutas%2C+Jack+Z&rft.inventor=Davidovich%2C+Martha&rft.inventor=Srivastava%2C+Sushil+K&rft.number=7838678&rft.date=2010-11-23&rft.externalDBID=n%2Fa&rft.externalDocID=07838678