Synthesis 2005(15): 2571-2577  
DOI: 10.1055/s-2005-872100
PAPER
© Georg Thieme Verlag Stuttgart · New York

Rapid and Efficient Microwave-Assisted Synthesis of 4-, 5-, 6- and 7-Azaindoles

Nicolas Lachance*, Myriam April, Marc-André Joly
Merck Frosst Centre for Therapeutic Research, P.O. Box 1005, Pointe Claire-Dorval, Québec, H9R 4P8, Canada
Fax: +1(514)4284900; e-Mail: nicolas_lachance@merck.com;
Further Information

Publication History

Received 28 February 2005
Publication Date:
29 July 2005 (eFirst)

Abstract

Under microwave irradiation conditions, the imines/enamines formed between aminopyridines and ketones are converted in moderate to good yields to the corresponding 4-, 5-, 6- or 7-azaindoles via the Hegedus-Mori-Heck reaction (intramolecular Heck reaction). A systematic examination of all isomeric azaindoles synthesis revealed this one-pot procedure to be general in scope.

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13

Pyrex cylindrical reaction tubes adapted to the Smith CreatorTM (Biotage/Personal Chemistry) were used. The temperature was measured by IR detection and maintained constant by modulated irradiation of 8-300 W.

15

Condensation of 3-amino-4-chloropyridine (22) with 1,3-cyclohexanedione (2.6 equiv) and PTSA (0.05 equiv) in refluxing benzene for 2.5 h delivered 5 (55%).

17

Absence of Pd(PPh3)4 resulted in the recovery of starting enamine 1.

23

For comparison, we have repeated the condensation step at 160 °C for 20 min with PPTS (0.05 equiv) for entries 4 and 5 from Table [3] . Azaindole 28 has been obtained in 62% isolated yield whereas only decomposition was observed when 22 and 25 were submitted to the same conditions.