937046-98-5Relevant articles and documents
Regioselective mono-bromination of pyrrolo[2,1-f][1,2,4]triazin-4-amine
Bi, Lei,Fang, Sheng,Zhang, Ran,Yin, Xianzhen,Fu, Chenchao,Yao, Lei
, p. 7083 - 7084 (2014)
Pyrrolo[2,1-f][1,2,4]triazin-4-amine is regioselectively brominated when treated with 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione in different solvents. The brominated product, 5,7-dibromopyrrolo[2,1-f][1,2,4]triazin-4-amine predominates when the reaction is run in dichloromethane. The subsequent debromination process utilizes lithium-bromine exchange to give the desired product 5-bromo-pyrrolo[2,1- f][1,2,4]triazin-4-amine.
Continuous Flow C-Glycosylation via Metal-Halogen Exchange: Process Understanding and Improvements toward Efficient Manufacturing of Remdesivir
Kappe, C. Oliver,Von Keutz, Timo,Williams, Jason D.
, p. 2362 - 2368 (2020/11/02)
As remdesivir is the first approved treatment for COVID-19 (SARS-CoV-2), its production is likely to be of vital importance in the near future. Continuous flow processing has been demonstrated as a key technology in the manufacturing of high-volume active pharmaceutical ingredients and is considered for use in this synthetic sequence. In particular, the challenging C-glycosylation of a pyrrolotriazinamine via metal-halogen exchange was identified as a transformation with significant potential benefit, as exemplified by calorimetric analysis of each reaction step. Multiple simplifications of this process were attempted in batch but in general were found to be unfruitful. The five-feed process was then transferred to a flow setup, where specific conditions were found to circumvent solid formation and permit stable processing. Detailed optimization of stoichiometries provided an improvement upon batch conditions with a total residence time of 1 min.
Preparation method 7-bromopyrrolo [2,1-f][1, 2, 4]-thiazine -4- amine (by machine translation)
-
, (2020/03/12)
[, ] The preparation method 7 - of [2,1 - f][1, 2, 4]-(, amino - ((((((((aopipelineao :1) aminopyrrolo 2,5 - thiopyrrole I,) obtained by reacting the intermediate 1 - Boc - 1 - with the formamidine in the following step ;2) can obtain the intermediate I (II, amino-(EC 1 - Boc - 1 -) to obtain the intermediate ;3), namely, II amino-(III, aminopyrrolopyrrole - 2 2-methanonitrile hydrochloride 1 -) to form the intermediate ;4) through the reaction of the intermediates III and the bromination reagent to obtain a final product IV, of the present invention. in an acidic condition and reacting the intermediate body with the bromination reagent. to obtain a final product (4 -aminopyrrolopyridine - 4 4) intermediate, [2,1 - f][1, 2, 4] [2,1 - f][1, 2, 4] obtained by the reaction of the intermediate body with the. bromination reagent and ;5) amino- pyrrolidine. IV-amine,aminopyrroyl hydrochloride 7 . (by machine translation)
SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF
-
Page/Page column 92, (2019/04/11)
Disclosed herein are compounds of the Formula (I) and pharmaceutically acceptable salts thereof: (I) where the variables in Formula (I) are described herein. Methods of synthesizing such compounds and methods of using them to treat diseases and/or conditi
Development of 4-Heteroarylamino-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octanes] as α7 Nicotinic Receptor Agonists
Hill, Matthew D.,Fang, Haiquan,King, H. Dalton,Iwuagwu, Christiana I.,McDonald, Ivar M.,Cook, James,Zusi, F. Christopher,Mate, Robert A.,Knox, Ronald J.,Post-Munson, Debra,Easton, Amy,Miller, Regina,Lentz, Kimberley,Clarke, Wendy,Benitex, Yulia,Lodge, Nicholas,Zaczek, Robert,Denton, Rex,Morgan, Daniel,Bristow, Linda,Macor, John E.,Olson, Richard
supporting information, p. 133 - 137 (2017/12/12)
We describe the synthesis of quinuclidine-containing spiroimidates and their utility as α7 nicotinic acetylcholine receptor (nAChR) partial agonists. A convergent synthetic route allowed for rapid SAR investigation and provided a diverse set of fused 6,5-heteroaryl analogs. Two potent and selective α7 nAChR partial agonists, (1′S,3′R,4′S)-N-(7-bromopyrrolo[2,1-f ][1,2,4]triazin-4-yl)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine (20) and (1′S,3′R,4′S)-N-(7-chloropyrrolo[2,1-f ][1,2,4]triazin-4-yl)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine (21), were identified. Both agonists improved cognition in a preclinical rodent model of learning and memory. Additionally, 5-HT3A receptor SAR suggested the presence of a steric site that when engaged led to significant loss of affinity at that receptor.
SUBSTITUTED 4-AMINO-PYRROLOTRIAZINE DERIVATIVES USEFUL FOR TREATING HYPER-PROLIFERATIVE DISORDERS AND DISEASES ASSOCIATED WITH ANGIOGENESIS
-
Page/Page column 164, (2010/11/27)
This invention relates to novel pyrrozolotriazine compounds, pharmaceutical compositions containing such compounds and and the use of those compounds or compositions for treating hyper-proliferative and/or angiogenesis disorders, as a sole agent or in combination with other active ingredients.
