US 12,269,839 B2
Chiral phosphoramidite auxiliaries and methods of their use
Sukumar Sakamuri, San Diego, CA (US); Curt W. Bradshaw, San Diego, CA (US); Dingguo Liu, San Diego, CA (US); and Laxman Eltepu, San Diego, CA (US)
Assigned to SIRIUS THERAPEUTICS, INC., Cambridge, MA (US)
Filed by Sirius Therapeutics, Inc., Boston, MA (US)
Filed on Jan. 9, 2023, as Appl. No. 18/094,723.
Application 18/094,723 is a continuation of application No. 16/627,091, granted, now 11,597,744, previously published as PCT/US2018/040592, filed on Jul. 2, 2018.
Claims priority of provisional application 62/527,078, filed on Jun. 30, 2017.
Prior Publication US 2023/0242567 A1, Aug. 3, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07H 19/11 (2006.01); C07H 19/213 (2006.01); C07H 21/04 (2006.01)
CPC C07H 19/11 (2013.01) [C07H 19/213 (2013.01); C07H 21/04 (2013.01)] 13 Claims
 
1. A method of preparing a composition comprising a nucleoside phosphoramidite, the method comprising coupling an oxazaphospholane with a nucleoside, wherein the nucleoside phosphoramidite is of the following structure:

OG Complex Work Unit Chemistry
wherein
B1 is a nucleobase;
Y1 is H or C1-6 alkyl;
custom character is a single carbon-carbon bond or a double carbon-carbon bond;
each of R1 and R2 is independently an optionally substituted C1-6 alkyl or optionally substituted C6-10 aryl, or R1 and R2, together with the atoms to which each is attached, combine to form an optionally substituted C6-10 aryl; and
each of R3 and R4 is H;
R5 is H, O-protected hydroxyl, optionally substituted C1-6 alkoxy, or halogen; and
R6 is a hydroxyl protecting group,
wherein the oxazaphospholane has a structure of Formula (VIIIA) or (VIIIB),

OG Complex Work Unit Chemistry
wherein X is halogen or pseudohalogen.