115932-00-8Relevant articles and documents
Efficient, Protecting Group Free Kilogram-Scale Synthesis of the JAK1 Inhibitor GDC-4379
Angelaud, Remy,Burkhard, Johannes,Gosselin, Francis,Lao, David,Marx, Andreas,Ochsenbein, Miriam,Ranjan, Rohit,Stumpf, Andreas,Xu, Di
, p. 2537 - 2550 (2021/11/24)
The development of an improved kilogram-scale synthesis of the JAK1 inhibitorGDC-4379for the treatment of asthma is described. The new process is highlighted by a step-economical construction of a 3-substituted-4-aminopyrazole employing a telescoped oximation and hydrazine condensation of a 1,3-dielectrophile to generate nitrosopyrazole and a novel copper-catalyzed NaBH4reduction of the nitroso group. The endgame process features an amidation of aminopyrazole with acid chloride under Schotten-Baumann conditions to provide access to the penultimate intermediate. A selective N-1 alkylation of the pyrazole moiety was accomplished under phase-transfer conditions, which deliveredGDC-4379with a defined particle-size distribution suitable for micronization after recrystallization and wet milling.
SUBSTITUTED HETEROARYL COMPOUNDS AND METHODS OF USE
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Paragraph 389, (2015/06/03)
The present invention provides novel heterocyclic compounds, pharmaceutical acceptable salts and formulations thereof useful in preventing, treating or lessening the severity of a JAK-mediated disease. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of JAK-mediated disease.
4,5-dihydro and 4,5,6,7-tetrahydropyrazolo(1,5-A)-pyrimidines
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, (2008/06/13)
Novel compounds having the following structural formula: STR1 wherein - - - may represent the presence of a double bond between the C6 and C7 position, Ia, or the absence of a double bond between the C6 and C7 position, Ib; R1 is selected from the group consisting essentially of hydrogen, bromo, chloro, carbamoyl, carboxyl, carboxyalkoxyl where alkoxyl is (C1 -C3), cyano, --CO--CF3, COONa, STR2 --CO--C(CH3)3, and STR3 where X is hydrogen, cyano, halogen and nitro; R2, R4 and R5 may be hydrogen and lower alkyl (C1 -C3); R3 is hydrogen, alkyl (C1 -C3), STR4 where R7 and R8 may be the same or different and are selected from the group consisting essentially of hydrogen, halogen, alkyl (C1 -C3), nitro, alkoxy (C1 -C3), trifluoro-methyl, acetylamino or N-alkylacetylamino where alkyl is (C1 -C3), and R3 may also be selected from a monovalent radical selected from the class consisting essentially of 3-thienyl, 2-pyridinyl, 3-pyridinyl and 4-pyridinyl, either of said pyridinyl radicals being optionally substituted with an alkyl radical R9, where alkyl is (C1 -C4), and the structures of the monovalent 2-pyridinyl, 3-pyridinyl and 4-pyridinyl moieties are depicted respectively as: STR5 R6 is hydrogen or alkyl-(C1 -C3); pharmaceutical compositions of matter containing the above-defined compounds; methods for using the compounds as anxiolytic agents, antihypertensive agents or antidepressant agents in mammals; processes for the preparation of the compounds.
