US 11,746,124 B2
Chemoselective thiol-conjugation with alkene or alkyne-phosphonamidates
Christian Hackenberger, Berlin (DE); Marc André Kasper, Berlin (DE); Maria Glanz, Berlin (DE); Tom Sauer, Rudolstadt (DE); Dominik Schumacher, Munich (DE); Jonas Helma-Smets, Munich (DE); Heinrich Leonhardt, Munich (DE); and Andreas Stengl, Munich (DE)
Assigned to FORSCHUNGSVERBUND BERLIN E.V., Berlin (DE); and LUDWIG-MAXIMILIANS-UNIVERSITÄT MÜNCHEN, München (unknown)
Filed by FORSCHUNGSVERBUND BERLIN E.V., Berlin (DE); and LUDWIG-MAXIMILIANS-UNIVERSITÄT MÜNCHEN, Munich (DE)
Filed on Aug. 30, 2021, as Appl. No. 17/460,791.
Application 17/460,791 is a division of application No. 16/328,199, granted, now 11,161,873, previously published as PCT/EP2017/071937, filed on Sep. 1, 2017.
Claims priority of application No. 16001917 (EP), filed on Sep. 1, 2016.
Prior Publication US 2022/0106356 A1, Apr. 7, 2022
Int. Cl. C07F 9/44 (2006.01); C07K 1/107 (2006.01); A61K 47/68 (2017.01); A61K 47/64 (2017.01); A61K 38/07 (2006.01)
CPC C07K 1/1077 (2013.01) [A61K 38/07 (2013.01); A61K 47/64 (2017.08); A61K 47/6803 (2017.08); A61K 47/6849 (2017.08); A61K 47/6855 (2017.08); A61K 47/6889 (2017.08); C07F 9/448 (2013.01); C07F 9/4461 (2013.01); C07F 9/4473 (2013.01)] 26 Claims
OG exemplary drawing
 
1. A compound of formula (V)

OG Complex Work Unit Chemistry
wherein:
custom character represents a triple bond;
X represents R3—C;
R1 independently represents an optionally substituted aliphatic or aromatic residue; optionally, R1 represents C1-C8-alkyl optionally substituted with at least one of (C1-C8-alkoxy)n wherein n is 1, 2, 3, 4, 5 or 6, F, Cl, Br, I, —NO2, —N(C1-C8-alkyl)H, —NH2, —N(C1-C8-alkyl)2, ═O, C3-C8-cycloalkyl, —S—S—(C1-C8-alkyl), hydroxy-(C1-C8-alkoxy)n wherein n is 1, 2, 3, 4, 5 or 6, C2-C8-alkynyl or optionally substituted phenyl; or
optionally, R1 represents phenyl optionally independently substituted with at least one of C1-C8-alkyl, (C1-C8-alkoxy)n wherein n is 1, 2, 3, 4, 5 or 6, F, Cl, I, Br, —NO2, —N(C1-C8-alkyl)H, —NH2 or —N(C1-C8-alkyl)2; or
optionally, R1 represents a 5- or 6-membered heteroaromatic system;
R3 represents H or C1-C8-alkyl;
and
● represents an aliphatic or aromatic residue.
 
12. A process for the preparation of a compound of formula (V), said process comprising the steps of:
(I) reacting compound of formula (III)

OG Complex Work Unit Chemistry
wherein:
custom character represents a double bond or a triple bond;
X represents R3—C when custom character is a triple bond; or
X represents CR3(R4) when custom character is a double bond;
R1 independently represents an optionally substituted aliphatic or aromatic residue;
optionally, R1 represents C1-C8-alkyl optionally substituted with at least one of (C1-C8-alkoxy)n wherein n is 1, 2, 3, 4, 5 or 6, F, Cl, Br, I, —NO2, —N(C1-C8-alkyl)H, —NH2, —N(C1-C8-alkyl)2, ═O, C3-C8-cycloalkyl, —S—S—(C1-C8-alkyl), hydroxy-(C1-C8-alkoxy)n wherein n is 1, 2, 3, 4, 5 or 6, C2-C8-alkynyl or optionally substituted phenyl; or
optionally, R1 represents phenyl optionally independently substituted with at least one of C1-C8-alkyl, (C1-C8-alkoxy)n wherein n is 1, 2, 3, 4, 5 or 6, F, Cl, I, Br, —NO2, —N(C1-C8-alkyl)H, —NH2 or —N(C1-C8-alkyl)2; or
optionally, R1 represents a 5- or 6-membered heteroaromatic system;
R3 represents H or C1-C8-alkyl; and
R4 represents H or C1-C8-alkyl;
with an azide of formula (IV)

OG Complex Work Unit Chemistry
wherein
● represents an aliphatic or aromatic residue;
to prepare a compound of formula (V)

OG Complex Work Unit Chemistry
wherein ●, custom character, R1, and X are as defined above.