Development of a Fit-for-Purpose Large-Scale Synthesis of an Oral PARP Inhibitor

Compound (1) a poly(ADP-ribose)polymerase (PARP) inhibitor has been made by a fit-for-purpose large-scale synthesis using either a classical resolution or chiral chromatographic separation. The development and relative merits of each route are discussed, along with operational improvements and exten...

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Published inOrganic process research & development Vol. 15; no. 4; pp. 831 - 840
Main Authors Wallace, Debra J, Baxter, Carl A, Brands, Karel J. M, Bremeyer, Nadine, Brewer, Sarah E, Desmond, Richard, Emerson, Khateeta M, Foley, Jennifer, Fernandez, Paul, Hu, Weifeng, Keen, Stephen P, Mullens, Peter, Muzzio, Daniel, Sajonz, Peter, Tan, Lushi, Wilson, Robert D, Zhou, George, Zhou, Guoyue
Format Journal Article
LanguageEnglish
Published American Chemical Society 15.07.2011
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Abstract Compound (1) a poly(ADP-ribose)polymerase (PARP) inhibitor has been made by a fit-for-purpose large-scale synthesis using either a classical resolution or chiral chromatographic separation. The development and relative merits of each route are discussed, along with operational improvements and extensive safety evaluations of potentially hazardous reactions.
AbstractList Compound (1) a poly(ADP-ribose)polymerase (PARP) inhibitor has been made by a fit-for-purpose large-scale synthesis using either a classical resolution or chiral chromatographic separation. The development and relative merits of each route are discussed, along with operational improvements and extensive safety evaluations of potentially hazardous reactions.
Author Wallace, Debra J
Fernandez, Paul
Emerson, Khateeta M
Zhou, George
Brands, Karel J. M
Mullens, Peter
Hu, Weifeng
Sajonz, Peter
Bremeyer, Nadine
Tan, Lushi
Zhou, Guoyue
Desmond, Richard
Wilson, Robert D
Muzzio, Daniel
Baxter, Carl A
Brewer, Sarah E
Foley, Jennifer
Keen, Stephen P
AuthorAffiliation Merck and Co
WuXi APPTec (Shanghai) Pharmaceutical Co. Ltd
Merck Research Laboratories
Merck Sharp and Dohme Research Laboratories
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Cites_doi 10.1016/0950-4230(93)90004-H
10.2741/2909
10.1021/op7000645
10.1021/jo048153i
10.1021/op0501803
10.1038/nrd1718
10.1021/ja054547v
10.1038/nature03443
10.1055/s-2000-7120
10.1038/nature03445
10.1016/j.bmcl.2009.11.127
10.1021/jo049011r
10.1021/jo060965m
10.1002/jhet.5570220130
10.1021/jo0524831
10.1021/jm901188v
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References Wiss J. (ref13/cit13a) 2006; 10
Fu X-L (ref6/cit6) 2009; 13
Dulenko V. I. (ref16/cit16a) 1986
Shirtcliff L. D. (ref4/cit4b) 2006; 71
Clark R. D. (ref10/cit10) 1985; 22
Julia M. (ref15/cit15) 1968; 3
ref16/cit16b
Scarpelli R. (ref3/cit3b) 2010; 20
Hassa P. O. (ref1/cit1a) 2008; 13
Farmer H. (ref2/cit2b) 2005; 434
ref3/cit3c
Shirtcliff L. D. (ref4/cit4a) 2004; 69
ref13/cit13c
Wiss J. (ref13/cit13b) 2007; 11
Hagtao P. (ref1/cit1b) 2005; 4
ref14/cit14
Bryant H. E. (ref2/cit2a) 2005; 434
Stoessel F. (ref7/cit7) 1993; 6
Jones P. (ref3/cit3a) 2009; 52
Shirtcliff L. D. (ref4/cit4c) 2006; 128
Mills A. D. (ref4/cit4d) 2006; 71
Kurth M. J. (ref4/cit4e) 2005; 70
Kuvshinov A. M. (ref5/cit5) 2000
References_xml – volume: 6
  start-page: 79
  year: 1993
  ident: ref7/cit7
  publication-title: J. Loss Prev. Process Ind.
  doi: 10.1016/0950-4230(93)90004-H
  contributor:
    fullname: Stoessel F.
– ident: ref14/cit14
– start-page: 44
  year: 1986
  ident: ref16/cit16a
  publication-title: Khim. Geterotsikl. Soedin.
  contributor:
    fullname: Dulenko V. I.
– volume: 13
  start-page: 3046
  year: 2008
  ident: ref1/cit1a
  publication-title: Front. Biosci
  doi: 10.2741/2909
  contributor:
    fullname: Hassa P. O.
– volume: 11
  start-page: 1096
  year: 2007
  ident: ref13/cit13b
  publication-title: Org. Process Res. Dev.
  doi: 10.1021/op7000645
  contributor:
    fullname: Wiss J.
– volume: 70
  start-page: 1060
  year: 2005
  ident: ref4/cit4e
  publication-title: J. Org. Chem.
  doi: 10.1021/jo048153i
  contributor:
    fullname: Kurth M. J.
– volume: 10
  start-page: 349
  year: 2006
  ident: ref13/cit13a
  publication-title: Org. Process Res. Dev.
  doi: 10.1021/op0501803
  contributor:
    fullname: Wiss J.
– volume: 4
  start-page: 421
  year: 2005
  ident: ref1/cit1b
  publication-title: Nat. Rev. Drug Discovery
  doi: 10.1038/nrd1718
  contributor:
    fullname: Hagtao P.
– volume: 128
  start-page: 9711
  year: 2006
  ident: ref4/cit4c
  publication-title: J. Am. Chem. Soc.
  doi: 10.1021/ja054547v
  contributor:
    fullname: Shirtcliff L. D.
– volume: 434
  start-page: 913
  year: 2005
  ident: ref2/cit2a
  publication-title: Nature (London)
  doi: 10.1038/nature03443
  contributor:
    fullname: Bryant H. E.
– start-page: 1474
  year: 2000
  ident: ref5/cit5
  publication-title: Synthesis
  doi: 10.1055/s-2000-7120
  contributor:
    fullname: Kuvshinov A. M.
– volume: 434
  start-page: 913
  year: 2005
  ident: ref2/cit2b
  publication-title: Nature (London)
  doi: 10.1038/nature03445
  contributor:
    fullname: Farmer H.
– volume: 20
  start-page: 488
  year: 2010
  ident: ref3/cit3b
  publication-title: Bio. Org. Med. Chem. Lett.
  doi: 10.1016/j.bmcl.2009.11.127
  contributor:
    fullname: Scarpelli R.
– ident: ref3/cit3c
– volume: 69
  start-page: 6979
  year: 2004
  ident: ref4/cit4a
  publication-title: J. Org. Chem.
  doi: 10.1021/jo049011r
  contributor:
    fullname: Shirtcliff L. D.
– volume: 71
  start-page: 6619
  year: 2006
  ident: ref4/cit4b
  publication-title: J. Org. Chem.
  doi: 10.1021/jo060965m
  contributor:
    fullname: Shirtcliff L. D.
– volume: 13
  start-page: 2051
  year: 2009
  ident: ref6/cit6
  publication-title: Eur. J. Org. Chem.
  contributor:
    fullname: Fu X-L
– ident: ref16/cit16b
– ident: ref13/cit13c
– volume: 22
  start-page: 121
  year: 1985
  ident: ref10/cit10
  publication-title: J. Heterocycl. Chem.
  doi: 10.1002/jhet.5570220130
  contributor:
    fullname: Clark R. D.
– volume: 3
  start-page: 987
  year: 1968
  ident: ref15/cit15
  publication-title: J. Bull. Soc. Chim. Fr.
  contributor:
    fullname: Julia M.
– volume: 71
  start-page: 2687
  year: 2006
  ident: ref4/cit4d
  publication-title: J. Org. Chem.
  doi: 10.1021/jo0524831
  contributor:
    fullname: Mills A. D.
– volume: 52
  start-page: 7170
  year: 2009
  ident: ref3/cit3a
  publication-title: J. Med. Chem.
  doi: 10.1021/jm901188v
  contributor:
    fullname: Jones P.
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Title Development of a Fit-for-Purpose Large-Scale Synthesis of an Oral PARP Inhibitor
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