Reversible carboxamide-mediated internal activation at C(6) of 2-chloro-4-anilino-1H-pyrrolo[2,3-d]pyrimidines.
A synthetic route to bisanilino-1H-pyrrolo[2,3-d]pyrimidines has been discovered, wherein the C(6)-chloride reactivity is necessarily enhanced via reversible acid-catalyzed internal activation of the pyrimidine ring by a C(1')-carboxamide moiety. Subsequent selective nucleophilic displacements at C(6) and C(1') constitute a one-pot tandem protocol for the rapid assembly of bisanilino-1H-pyrrolo[2,3-d]pyrimidines.
Chamberlain
Stanley D
SD
GlaxoSmithKline, Oncology R&D, 5 Moore Drive, Research Triangle Park, North Carolina 27709, USA.
Gerding
Roseanne M
RM
Lei
Huangshu
H
Moorthy
Ganesh
G
Patnaik
Samarjit
S
Redman
Anikó M
AM
Stevens
Kirk L
KL
Wilson
Joseph W
JW
Yang
Bin
B
Shotwell
J Brad
JB
D000577:Amides / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods*; D002712:Chlorides / Q000737:chemistry; D015195:Drug Design; D008956:Models, Chemical; D011743:Pyrimidines / Q000737:chemistry*; D011758:Pyrroles / Q000737:chemistry*
C538706:4,6-bis-anilino-1H-pyrrolo(2,3-d)pyrimidine; D000577:Amides; D002712:Chlorides; D011743:Pyrimidines; D011758:Pyrroles; D002244:Carbon