US 12,391,716 B2
Process of preparing nucleic acid oligomer
Takuya Miyagawa, Osaka (JP)
Assigned to SUMITOMO CHEMICAL COMPANY, LIMITED, Chuo-ku (JP)
Appl. No. 17/792,484
Filed by SUMITOMO CHEMICAL COMPANY, LIMITED, Chuo-ku (JP)
PCT Filed Jan. 29, 2021, PCT No. PCT/JP2021/003351
§ 371(c)(1), (2) Date Jul. 13, 2022,
PCT Pub. No. WO2021/153770, PCT Pub. Date Aug. 5, 2021.
Claims priority of application No. 2020-012789 (JP), filed on Jan. 29, 2020.
Prior Publication US 2023/0095584 A1, Mar. 30, 2023
Int. Cl. C07H 1/00 (2006.01); C07H 13/00 (2006.01); C07H 21/02 (2006.01)
CPC C07H 1/00 (2013.01) [C07H 13/00 (2013.01); C07H 21/02 (2013.01)] 23 Claims
 
1. A process for preparing, by a phosphoramidite method, a nucleic acid compound having at its 5′-terminus a nucleotide represented by the following formula (I):

OG Complex Work Unit Chemistry
wherein
G1 and G2 each independently represent a protecting group for a hydroxy group, and Ba represents a nucleic acid base which may be optionally protected with a protecting group,
R represents a protected hydroxy group, a hydrogen atom, a fluorine atom, a methoxy group, a 2-methoxyethyl group, or a OQ′ group,
Q′ represents a methylene group attached to a carbon atom at 4′-position of ribose, an ethylene group attached to a carbon atom at 4′-position of ribose, or an ethylidene group attached to a carbon atom at 4′-position of ribose, and
* represents a bond directing to 3′ terminus side of a nucleic acid,
the process comprising:
reacting a precursor having a phosphite triester bond represented by the following formula (II):

OG Complex Work Unit Chemistry
wherein
G1, G2, Ba, R and * are the same in the formula (I)
wherein the reacting the precursor having a phosphite triester bond is conducted in an oxidation solution which is at 40° C. or higher and comprises iodine, pyridine and water.