Reductive sp 3 -sp 2 Coupling Reactions Enable Late-Stage Modification of Pharmaceuticals

Late-stage derivatization of pharmaceutically relevant scaffolds relies on the availability of highly functional-group tolerant reactions. Reactions that increase the sp character of molecules enable the pursuit of more selective and well-tolerated pharmaceuticals. Herein, we report the use of sp -s...

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Published inOrganic letters Vol. 22; no. 2; pp. 556 - 559
Main Authors Mennie, Katrina M, Vara, Brandon A, Levi, Samuel M
Format Journal Article
LanguageEnglish
Published United States 17.01.2020
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Abstract Late-stage derivatization of pharmaceutically relevant scaffolds relies on the availability of highly functional-group tolerant reactions. Reactions that increase the sp character of molecules enable the pursuit of more selective and well-tolerated pharmaceuticals. Herein, we report the use of sp -sp cross-electrophile reductive couplings to modify a generic ATP-competitive kinase inhibitor with a broad range of primary and secondary alkyl halide coupling partners.
AbstractList Late-stage derivatization of pharmaceutically relevant scaffolds relies on the availability of highly functional-group tolerant reactions. Reactions that increase the sp character of molecules enable the pursuit of more selective and well-tolerated pharmaceuticals. Herein, we report the use of sp -sp cross-electrophile reductive couplings to modify a generic ATP-competitive kinase inhibitor with a broad range of primary and secondary alkyl halide coupling partners.
Author Vara, Brandon A
Levi, Samuel M
Mennie, Katrina M
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/31909629$$D View this record in MEDLINE/PubMed
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Cites_doi 10.1002/chem.201402302
10.1021/acs.oprd.9b00232
10.1038/nature13274
10.1002/adsc.200404223
10.1002/chem.201601320
10.1158/0008-5472.CAN-07-2667
10.1021/acs.orglett.9b01097
10.1021/cr100327p
10.1021/acs.accounts.5b00057
10.1073/pnas.0609412103
10.1002/anie.200803611
10.1021/jo500905m
10.1158/1535-7163.MCT-06-0476
10.1021/ja301769r
10.1002/anie.200804434
10.1002/mc.20297
10.1002/chem.201000178
10.1038/nchem.2587
10.1021/acs.oprd.9b00140
10.1021/jacs.6b09533
10.1021/acscentsci.8b00728
10.1016/j.tet.2006.11.055
10.1039/b809626k
10.1016/j.chembiol.2017.10.005
10.1126/science.1259203
10.1039/C9RE00234K
10.1039/c2cc33232a
10.1080/14737140.2018.1527688
10.1021/jo801063c
10.1021/jm901241e
10.1021/jacs.6b04818
10.1021/jo500507s
10.1021/acsmedchemlett.7b00165
10.1021/ja906803t
10.1055/s-0029-1218012
10.1039/c2md20347b
10.1021/ja9093956
10.1021/acs.joc.7b01334
10.1002/anie.201509341
10.1021/ja407589e
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References ref9/cit9
ref3/cit3
ref15/cit15a
ref15/cit15d
ref15/cit15e
ref2/cit2e
ref15/cit15b
ref2/cit2d
ref15/cit15c
ref16/cit16
ref15/cit15f
ref12/cit12b
ref12/cit12a
ref2/cit2c
ref8/cit8
ref2/cit2b
ref5/cit5
ref2/cit2a
ref1/cit1a
ref1/cit1b
ref17/cit17
ref10/cit10
ref4/cit4a
ref4/cit4b
ref4/cit4c
ref14/cit14a
ref19/cit19
ref14/cit14c
ref14/cit14b
ref11/cit11c
ref11/cit11b
ref14/cit14d
ref11/cit11d
ref11/cit11a
ref13/cit13
ref7/cit7b
ref7/cit7a
ref4/cit4d
ref6/cit6a
ref6/cit6b
References_xml – ident: ref2/cit2e
  doi: 10.1002/chem.201402302
– ident: ref16/cit16
  doi: 10.1021/acs.oprd.9b00232
– ident: ref2/cit2b
  doi: 10.1038/nature13274
– ident: ref2/cit2c
  doi: 10.1002/adsc.200404223
– ident: ref11/cit11b
  doi: 10.1002/chem.201601320
– ident: ref15/cit15e
  doi: 10.1158/0008-5472.CAN-07-2667
– ident: ref12/cit12b
  doi: 10.1021/acs.orglett.9b01097
– ident: ref2/cit2a
  doi: 10.1021/cr100327p
– ident: ref11/cit11c
  doi: 10.1021/acs.accounts.5b00057
– ident: ref15/cit15d
  doi: 10.1073/pnas.0609412103
– ident: ref2/cit2d
  doi: 10.1002/anie.200803611
– ident: ref12/cit12a
  doi: 10.1021/jo500905m
– ident: ref15/cit15b
  doi: 10.1158/1535-7163.MCT-06-0476
– ident: ref11/cit11a
  doi: 10.1021/ja301769r
– ident: ref7/cit7a
  doi: 10.1002/anie.200804434
– ident: ref15/cit15c
  doi: 10.1002/mc.20297
– ident: ref6/cit6a
  doi: 10.1002/chem.201000178
– ident: ref4/cit4a
  doi: 10.1038/nchem.2587
– ident: ref14/cit14c
  doi: 10.1021/acs.oprd.9b00140
– ident: ref4/cit4d
  doi: 10.1021/jacs.6b09533
– ident: ref19/cit19
  doi: 10.1021/acscentsci.8b00728
– ident: ref5/cit5
  doi: 10.1016/j.tet.2006.11.055
– ident: ref6/cit6b
  doi: 10.1039/b809626k
– ident: ref15/cit15f
  doi: 10.1016/j.chembiol.2017.10.005
– ident: ref14/cit14a
  doi: 10.1126/science.1259203
– ident: ref14/cit14b
  doi: 10.1039/C9RE00234K
– ident: ref10/cit10
  doi: 10.1039/c2cc33232a
– ident: ref15/cit15a
  doi: 10.1080/14737140.2018.1527688
– ident: ref8/cit8
  doi: 10.1021/jo801063c
– ident: ref1/cit1a
  doi: 10.1021/jm901241e
– ident: ref4/cit4c
  doi: 10.1021/jacs.6b04818
– ident: ref11/cit11d
  doi: 10.1021/jo500507s
– ident: ref14/cit14d
  doi: 10.1021/acsmedchemlett.7b00165
– ident: ref9/cit9
  doi: 10.1021/ja906803t
– ident: ref7/cit7b
  doi: 10.1055/s-0029-1218012
– ident: ref1/cit1b
  doi: 10.1039/c2md20347b
– ident: ref3/cit3
  doi: 10.1021/ja9093956
– ident: ref4/cit4b
  doi: 10.1021/acs.joc.7b01334
– ident: ref13/cit13
  doi: 10.1002/anie.201509341
– ident: ref17/cit17
  doi: 10.1021/ja407589e
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