- KCNT1 INHIBITORS AND METHODS OF USE
-
The present invention is directed to, in part, compounds and compositions useful for preventing and/or treating a neurological disease or disorder, a disease or condition relating to excessive neuronal excitability, and/or a gain-of-function mutation in a gene (e.g., KCNT1). Methods of treating a neurological disease or disorder, a disease or condition relating to excessive neuronal excitability, and/or a gain-of-function mutation in a gene such as KCNT1 are also provided herein.
- -
-
Paragraph 000386; 000830
(2020/11/23)
-
- Direct [3+2]-cycloaddition of electron-deficient alkynes with CF3CHN2: Regioselective one-pot synthesis of 3-trifluoromethylpyrazoles
-
A direct and facile cycloaddition reaction of electron-deficient terminal alkynes with 2,2,2-trifluorodiazoethane under mild conditions to afford a series of 5-substituted 3-trifluoromethylpyrazoles in high yields is described. The potential application of this cycloaddition reaction was demonstrated via the efficient synthesis of a key intermediate of the antiviral drug AS-136A and a fluorinated analog of Tebufenpyrad.
- Li, Feng,Wang, Jingjing,Pei, Wenlong,Li, Hong,Zhang, Huiling,Song, Manman,Guo, Linyun,Zhang, Anan,Liu, Lantao
-
p. 4344 - 4347
(2017/10/17)
-
- A Unified Continuous Flow Assembly-Line Synthesis of Highly Substituted Pyrazoles and Pyrazolines
-
A rapid and modular continuous flow synthesis of highly functionalized fluorinated pyrazoles and pyrazolines has been developed. Flowing fluorinated amines through sequential reactor coils mediates diazoalkane formation and [3+2] cycloaddition to generate more than 30 azoles in a telescoped fashion. Pyrazole cores are then sequentially modified through additional reactor modules performing N-alkylation and arylation, deprotection, and amidation to install broad molecular diversity in short order. Continuous flow synthesis enables the safe handling of diazoalkanes at elevated temperatures, and the use of aryl alkyne dipolarphiles under catalyst-free conditions. This assembly-line synthesis provides a flexible approach for the synthesis of agrochemicals and pharmaceuticals, as demonstrated by a four-step, telescoped synthesis of measles therapeutic, AS-136A, in a total residence time of 31.7 min (1.76 g h?1).
- Britton, Joshua,Jamison, Timothy F.
-
supporting information
p. 8823 - 8827
(2017/07/17)
-
- Synthesis of Celecoxib, Mavacoxib, SC-560, Fluxapyroxad, and Bixafen Enabled by Continuous Flow Reaction Modules
-
Multi-step continuous flow synthesis enables a parallel approach to obtain agrochemicals and pharmaceuticals containing 3-fluoroalkyl pyrazole cores. In this system, fluorinated amines are transformed into pyrazole cores through a telescoped in situ generation and consumption of diazoalkanes. Once synthesized, additional continuous flow and batch reactions add complexity to the pyrazole core via C–N arylation and methylation, TMS cleavage, and amidation. Using this modular assembly line approach, Bixafen and Fluxapyroxad were synthesized in 38 % yield over four continuous flow steps in an overall reaction time of 56 min. Finally, coupling selected continuous flow processes with an offline (batch) Ullmann coupling afforded Celecoxib, Mavacoxib, and SC-560 in 33–54 % yield over two to three steps.
- Britton, Joshua,Jamison, Timothy F.
-
p. 6566 - 6574
(2017/12/02)
-
- Fluoroalkyl-Substituted Diazomethanes and Their Application in a General Synthesis of Pyrazoles and Pyrazolines
-
A novel continuous-flow approach for the synthesis of fluoroalkyl-substituted diazomethanes has been developed. Utilizing a cheap, self-made microreactor fluoroalkyl-substituted amines were transformed into the corresponding diazomethanes using tert-butyl nitrite and acetic acid as catalyst. These diazomethanes were employed in [2+3] cycloaddition reactions with olefins and alkynes, yielding valuable pyrazolines and pyrazoles in good to excellent yields.
- Mertens, Lucas,Hock, Katharina J.,Koenigs, Rene M.
-
supporting information
p. 9542 - 9545
(2016/07/14)
-
- Silver-mediated cycloaddition of alkynes with CF3CHN 2: Highly regioselective synthesis of 3-trifluoromethylpyrazoles
-
Silver screen: The title reaction provides a convenient and efficient method for the construction of 5-substituted 3-trifluoromethylpyrazoles under mild reaction conditions. By using this protocol, the marketed drug Celecoxib (antiarthritic) could be easily synthesized (see scheme; DMF=N,N- dimethylformamide). Copyright
- Li, Feng,Nie, Jing,Sun, Long,Zheng, Yan,Ma, Jun-An
-
p. 6255 - 6258
(2013/07/05)
-
- Facile conversion of trifluoroacetyltriphenylsilane 2,4,6-triisepropylbenzenesulfonylhydrazone to 2,2,2-trifluorodiazoethane. An unusual example of the Bamford-Stevens reaction
-
Trifluoroacetyltriphenylsilane 2,4,6-triisepropylbenzenesulfonylhydrazone(1) reacted with dipolarophiles in the presence of Et3N to produce trifluorcmethylated pyrazoles or pyrazolines in good yields. The reaction was found to proceed through t
- Jin, Fuqiang,Xu, Yuanyao,Ma, Yiling
-
p. 6161 - 6164
(2007/10/02)
-
