On August 31, 2017, Chappie, Thomas Allen; Patel, Nandini Chaturbhai; Verhoest, Patrick Robert; Helal, Christopher John; Sciabola, Simone; Lachapelle, Erik Alphie; Wager, Travis T.; Hayward, Matthew Merrill published a patent.Reference of Ethyl 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate The title of the patent was 6,7-Dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide compounds as PDE4 inhibitors and their preparation. And the patent contained the following:
The invention is directed to PDE4B inhibitors of formula Ior a pharmaceutically acceptable salt thereof. The invention is also directed to pharmaceutical compositions comprising the compounds, methods of treatment using the compounds, and methods of preparing the compounds Compounds of formula I wherein R1 is (un)substituted C3-8 cycloalkyl, (un)substituted C6-10 aryl, (un)substituted 5- to 10-membered heteroaryl, etc.; R2 and R3 are independently H, (un)substituted C1-6 alkyl, (un)substituted C3-8 cycloalkyl, (un)substituted C6-10 aryl, etc.; n is 0, 1, 2 and 3; each R4 is independently halo, CN, OH, SF5, NO2, etc.; and pharmaceutically acceptable salts thereof, are claimed. Example compound II was prepared by cross-coupling of azetidin-1-yl(3-bromo-6,7-dihydro-5H-pyrazolo[5,1-b]oxazin-2-yl)methanol with 4-chloro-2-methylphenylboronic acid. The invention compounds were evaluated for their PDE4 inhibitory activity. From the assay, it was determined that compound II exhibited IC50 values of 211 nM, 241 nM and 653 nM towards PDE4B1, PDE4A3 and PDE4C1, resp. The experimental process involved the reaction of Ethyl 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate(cas: 153597-59-2).Reference of Ethyl 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate
The Article related to pyrazolooxazinecarboxamide preparation pde4 inhibitor, Heterocyclic Compounds (More Than One Hetero Atom): Oxazines (Including Morpholine) and other aspects.Reference of Ethyl 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate
Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics