US 12,077,558 B2
Phosphorus (V)-based reagents, processes for the preparation thereof, and their use in making stereo-defined organophosphorus (V) compounds
Michael Anthony Schmidt, Cranbury, NJ (US); Bin Zheng, Kendall Park, NJ (US); Kyle Knouse, New Oxford, PA (US); Justine deGruyter, College Station, TX (US); Martin D. Eastgate, Titusville, NJ (US); Phil Baran, San Diego, CA (US); William R. Ewing, Yardley, PA (US); Richard E. Olson, Cambridge, MA (US); and Ivar M. McDonald, Woodstock, CT (US)
Assigned to Bristol-Myers Squibb Company, Princeton, NJ (US); and The Scripps Research Institute, La Jolla, CA (US)
Filed by Bristol-Myers Squibb Company, Princeton, NJ (US); and The Scripps Research Institute, La Jolla, CA (US)
Filed on Feb. 10, 2023, as Appl. No. 18/167,772.
Application 18/167,772 is a division of application No. 16/382,692, filed on Apr. 12, 2019, granted, now 11,613,554.
Claims priority of provisional application 62/729,314, filed on Sep. 10, 2018.
Claims priority of provisional application 62/697,896, filed on Jul. 13, 2018.
Claims priority of provisional application 62/668,098, filed on May 7, 2018.
Claims priority of provisional application 62/657,551, filed on Apr. 13, 2018.
Prior Publication US 2023/0242569 A1, Aug. 3, 2023
Int. Cl. C07H 21/00 (2006.01); C07H 19/11 (2006.01); C07H 19/213 (2006.01)
CPC C07H 21/00 (2013.01) 20 Claims
 
1. A stereochemically pure compound of formula IV:

OG Complex Work Unit Chemistry
wherein
(a) R1, R2, R3, R4, R5, and R6 are independently hydrogen, CD3, CF3, linear or branched C1-C20 alkyl, optionally substituted with one or more, the same or different, Ra groups; linear or branched C2-C12 alkenyl; optionally substituted with one or more, the same or different, Ra groups; linear or branched C2-C12 alkynyl, optionally substituted with one or more, the same or different, Ra groups; aryl, optionally substituted with one or more, the same or different, Ra groups; heteroaryl, optionally substituted with one or more, the same or different, Ra groups; heterocyclyl, optionally substituted with one or more, the same or different, Ra groups; or C3-C8 cycloalkyl, optionally substituted with one or more, the same or different, Ra groups; or
(b) any two of R1, R2, R3, R4, R5, and R6 together with the carbons to which they are attached form a C4-C8 cycloalkyl group, optionally substituted with one or more, the same or different, Ra groups, while the remaining R1, R2, R3, R4, R5, and R6 are as defined in (a);
Ra is hydrogen, deuterium, CD3, C1-C6 alkyl, OH, halogen, CN, CF3, O—C1-C6 alkyl, O-aryl, O-heteroaryl, O—C3-C8 cycloalkyl, O-heterocyclyl, —NRbRb, —COORb or —CONRbRb;
Rb is independently at each occurrence, the same or different, hydrogen, linear or branched C1-C12 alkyl, aryl, heteroaryl, heterocyclyl or C3-C8 cycloalkyl;
X1 is O, X2 is S; or X1 is S, X2 is O;
Y is O, S or NRc;
Rc is hydrogen;
m is 0, 1 or 2, and
Nu is a nucleoside, wherein the phosphorus atom is covalently bonded to a 5′- or 3′-oxygen atom on the nucleoside sugar;
with the proviso that the compound of formula IV does not include the following compounds:

OG Complex Work Unit Chemistry