Efficient N-arylation/dealkylation of electron deficient heteroaryl chlorides and bicyclic tertiary amines under microwave irradiation.
A highly efficient procedure was developed for the microwave-assisted synthesis of N-heteroaryl-4-(2-chloroethyl)piperazines and N-heteroaryl-4-(2-chloroethyl)piperidines. Microwave irradiation of electron deficient heteroaryl chlorides with 1,4-diazabicyclo[2.2.2]octane (DABCO) at 160 degrees C for 15 min led to N-heteroaryl-4-(2-chloroethyl)piperazines in good to excellent yields. In a similar manner, microwave irradiation of electron deficient heteroaryl chlorides with quinuclidine at 180 degrees C for 15 min provided N-heteroaryl-4-(2-chloroethyl)piperidines in good to excellent yields. Extension of the method was demonstrated by the development of a one-pot, two-step microwave-assisted protocol for the synthesis of 4-(2-acetoxyethyl)-substituted N-heteroarylpiperazines and N-heteroarylpiperidines to demonstrate the production of a small library in a parallel fashion.
Wang
Hong-Jun
HJ
Medicinal Chemistry Department, Albany Molecular Research, Inc (AMRI), Albany, New York 12212, USA. Hong-Jun.Wang@amriglobal.com
Wang
Yi
Y
Csakai
Adam J
AJ
Earley
William G
WG
Herr
R Jason
RJ
D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry*; D002712:Chlorides / Q000138:chemical synthesis / Q000737:chemistry*; D008872:Microwaves; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry; D011812:Quinuclidines / Q000138:chemical synthesis / Q000737:chemistry; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000737:chemistry / Q000191:economics
D000588:Amines; D002712:Chlorides; D010879:Piperazines; D010880:Piperidines; D011812:Quinuclidines; D054852:Small Molecule Libraries; C007306:triethylenediamine