US 12,344,619 B2
Drug delivery and imaging chemical conjugate, formulations and methods of use thereof
Steven Jay Adelman, Doylestown, PA (US); H. Donlon Skerrett, Wayne, PA (US); and William A. Kinney, Newtown, PA (US)
Assigned to NANOPHAGIX, Berwyn, PA (US)
Filed by NANOPHAGIX LLC, Berwyn, PA (US)
Filed on May 26, 2021, as Appl. No. 17/330,417.
Application 17/330,417 is a continuation of application No. 15/580,313, granted, now 11,034,701, previously published as PCT/US2016/037580, filed on Jun. 15, 2016.
Claims priority of provisional application 62/180,111, filed on Jun. 16, 2015.
Prior Publication US 2021/0277016 A1, Sep. 9, 2021
Int. Cl. C07D 491/153 (2006.01); A61K 47/54 (2017.01); A61P 1/00 (2006.01); A61P 9/10 (2006.01); A61P 19/02 (2006.01); A61P 29/00 (2006.01); A61P 35/00 (2006.01); C07D 491/18 (2006.01)
CPC C07D 491/153 (2013.01) [A61K 47/542 (2017.08); A61P 1/00 (2018.01); A61P 9/10 (2018.01); A61P 19/02 (2018.01); A61P 29/00 (2018.01); A61P 35/00 (2018.01); C07D 491/18 (2013.01)] 6 Claims
 
1. A process for preparing a product, comprising the steps:
coupling a secondary alcohol at carbon position 43 of rapamycin with a bromo-substituted acyl chloride to obtain an intermediate A, wherein R is X-L-Br,

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reacting intermediate A at room temperature in one portion to a solution of a sodium salt of a compound of Formula 1 in dimethylformamide:

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wherein,
X is carbonyl or a bond;
Y and Z are each independently selected from the group consisting of bond, oxygen, carbonyl, and amine, and Y having a point of attachment to L;
L is a linker comprising at least one selected from the group consisting of a bond, an alkyl, a branched alkyl, an aryl, an ester, an ether, and an amide;
R1, R2, R3, R4, and R5 are each independently selected from the group consisting of H, F, Cl, Br, I, NR6R7, NR6C(═O)R7, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, wherein R6 and R7 are selected from the group consisting of H, and optionally substituted C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl;
n is 1 or 2;
under reaction conditions effective to obtain a product of the formula

OG Complex Work Unit Chemistry