244081-35-4Relevant academic research and scientific papers
INDOLE, INDAZOLE, AND BENZAZOLE DERIVATIVE
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Page/Page column 56, (2010/02/11)
The compound of the formula (I): wherein W is a group of the following formula (VIII) binding to any possible position on the Q: Q is, together with W, a group of the formula: -C(M=C(R3A)-N(R3)-, etc.; R3A is H or optionally substituted lower alkyl; R4, R5, R6, and R7 are independently H or optionally substituted lower alkyl; R1 is optionally substituted lower alkyl, etc.; R2 is H, etc.; R3 is H, etc.; Ar is phenyl, etc., or a pharmaceutically acceptable salt thereof, where these compounds exhibiting β3-adrenoceptor-stimulating activity and being useful as a medicament for treatment of obesity, etc.
Process development of a scaleable route to (2R)-[3-(2-Aminopropyl)-1H- indol-7-yloxy]-N,N-diethylacetamide: A key intermediate for AJ-9677, a potent and selective human and rat β3-adrenergic receptor agonist
Harada, Hiroshi,Fujii, Akihito,Odai, Osamu,Kato, Shiro
, p. 238 - 245 (2013/09/04)
(2R)-[3-(2-Aminopropyl)-1H-indol-7-yloxy]acetic acid (2) is the left-hand side segment of AJ-9677, which is a potent and selective human and rat β3-adrenergic receptor agonist. Herein, we describe the process development of a scaleable synthetic route to the corresponding N,N-diethylacetamide derivative 3 of 2 from 7-benzyloxy-1H-indole (4). Reaction of the indole Grignard reagent 12 generated from 4 and methylmagnesium bromide with the N-Fmoc-D-alanyl chloride 22, followed by reduction of the resulting crude 3-acylindole 26 with NaBH4 in a mixture of MeCN and 2-PrOH at refluxing temperature and subsequent treatment with oxalic acid gave the oxalate of the N-deprotected product, (2R)-3-(2-aminopropyl)-7-benzyloxy-1H- indole [(R)-7] as a crystalline material in 60% yield. After N-protection of the (R)-7 by Boc group, the (2R)-3-[2-(Boc-amino)propyl]-1H-indole 30 was hydrogenated to provide the (2R)-3-(2-aminopropyl)-7-hydroxy-1H-indole 31, which was subsequently alkylated with ClCH2CONEt2 to give 32 in 91% yield. Finally, treatment of 32 with oxalic acid afforded the desired 3 in 79% in >99% ee.
A scalable synthesis of (R)-3-(2-aminopropyl)-7-benzyloxyindole via resolution
Fujii, Akihito,Fujima, Yoshito,Harada, Hiroshi,Ikunaka, Masaya,Inoue, Toru,Kato, Shiro,Matsuyama, Keisuke
, p. 3235 - 3240 (2007/10/03)
(±)-3-(2-Aminopropyl)-7-benzyloxyindole 1, assembled from 7-benzyloxyindole 3 in 59% overall yield, is resolved with O,O′-di-p-toluoyl L-(2R,3R)-tartaric acid 7 into (R)-1, a key intermediate of AJ-9677 2 (selective adrenaline β3-agonist) in 99
