Synthesis of Annulated Pyridines by Intramolecular Inverse-Electron-Demand Hetero-Diels-Alder Reaction under Superheated Continuous Flow Conditions
作者:Rainer E. Martin、Falk Morawitz、Christoph Kuratli、André M. Alker、Alexander I. Alanine
DOI:10.1002/ejoc.201101538
日期:2012.1
materials was investigated and a scalable flow process was developed, providing facile access to a series of novel annulatedpyridine building blocks. The effect of thermal volume expansion of solvents undersuperheatedconditions was found to be significant and influenced the residence times considerably. To obtain meaningful and accurate residence times, flow rates need to be corrected for volume expansion
The reactions of 2-amino-4,5-dihydro-3-furancarbonitriles 1a-d with α,β-unsaturated carbonyl compounds in the presence of sodium ethoxide (0.1 equivalent) gave the corresponding Michael adducts 2a-d, 3a-d and 4a-d. Compounds 2a-d and 3a-c reacted with sodium alkoxide (1 equivalent) to yield the corresponding 7a-alkoxyhexahydrofuro[2,3-b]pyridines 5a-d, 6a-d, 7a-c and 8a-c. Treatment of 5a-d, 6a-d,
2-氨基-4,5-二氢-3-呋喃腈1a-d与α,β-不饱和羰基化合物在乙醇钠(0.1当量)存在下的反应得到相应的迈克尔加合物2a-d,3a-d和4a-d。化合物2a-d和3a-c与醇钠(1当量)反应,得到相应的7a-烷氧基六氢呋喃[2,3- b ]吡啶5a-d,6a-d,7a-c和8a-c。用叔丁醇钾处理5a-d,6a-d,7a-c和8a-c产生相应的二氢呋喃并[2,3- b ]吡啶图9a-d和10a-c。4a-c与乙醇钠(1当量)反应,得到相应的二氢呋喃[2,3- b ]吡啶11a-c。
The present invention provides a nitrogen-containing saturated heterocyclic compound of the formula [I]:
wherein R
1
is a cycloalkyl group and the like, R
22
is an optionally substituted aryl and the like, R is a lower alkyl and the like, T is a carbonyl group, Z is —O— and the like, and R
3
to R
6
are the same or different and a hydrogen atom and the like;
or a pharmaceutically acceptable salt, that is useful as a renin inhibitor.