US 11,939,325 B2
Process for making biologically active compounds and intermediates thereof
Alexandros Makriyannis, Watertown, MA (US); and Kiran Vemuri, Boston, MA (US)
Assigned to MAKScientific, LLC, Burlington, MA (US)
Filed by MAKScientific, LLC, Burlington, MA (US)
Filed on Jul. 26, 2021, as Appl. No. 17/443,336.
Claims priority of provisional application 63/056,896, filed on Jul. 27, 2020.
Prior Publication US 2022/0024910 A1, Jan. 27, 2022
Int. Cl. C07D 417/12 (2006.01); C07B 59/00 (2006.01); C07D 401/12 (2006.01)
CPC C07D 417/12 (2013.01) [C07B 59/002 (2013.01); C07D 401/12 (2013.01); C07B 2200/05 (2013.01)] 12 Claims
 
1. A process for preparing a compound represented by Formula IA, its solvates, polymorphs and isotopic variations thereof:

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comprising:
reacting a compound represented by Formula II:

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with a compound represented by Formula III:

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to provide a compound represented by Formula VII:

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and
reacting the compound of Formula VII with an alkyne to provide a compound represented by formula I:

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or
reacting a compound represented by Formula II:

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with a compound represented by Formula III:

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to provide a compound represented by Formula I:

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and
reacting the compound of Formula I with an alkali metal hydroxide to provide a compound represented by Formula V:

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and
reacting the compound of Formula V with a substituted hydrazine to provide a compound represented by the Formula IA; or
reacting the compound of Formula I with a substituted hydrazine to provide a compound represented by Formula VI:

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and
reacting the compound of Formula VI with a divinyl derivative to provide a compound represented by the Formula IA, wherein
R is selected from the group consisting of H, CH3 and CH2CH3;
R1 is selected from the group consisting of H, CN, OH, phthalimido, amide, carboxylic ester, nitrate ester, halogen, methoxy, mesylate and tosylate;
R2 is selected from the group consisting of H, CH3, CH2CH3, OCH3 and CN;
X1 is selected from the group consisting of CH2, O and SO2;
X2 is halogen or

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n is an integer from 1-4; and
Y is selected from the group consisting of a C1-C4 alkyl group, a C1-C4 perfluoroalkyl group, and a phenyl group that is unsubstituted or substituted with a methyl, chloro or nitro group.