US 12,331,072 B2
Deprotection method and resin removal method in solid-phase reaction for peptide compound or amide compound, and method for producing peptide compound
Kotaro Iwasaki, Tokyo (JP); and Shio Komiya, Tokyo (JP)
Assigned to CHUGAI SEIYAKU KABUSHIKI KAISHA, Tokyo (JP)
Filed by Chugai Seiyaku Kabushiki Kaisha, Tokyo (JP)
Filed on May 30, 2023, as Appl. No. 18/203,371.
Application 18/203,371 is a continuation of application No. 17/297,231, granted, now 11,732,002, previously published as PCT/JP2019/046805, filed on Nov. 29, 2019.
Claims priority of application No. 2018-225518 (JP), filed on Nov. 30, 2018; application No. 2019-101971 (JP), filed on May 31, 2019; and application No. 2019-158173 (JP), filed on Aug. 30, 2019.
Prior Publication US 2023/0303619 A1, Sep. 28, 2023
Int. Cl. C07K 1/06 (2006.01); C07C 231/00 (2006.01)
CPC C07K 1/06 (2013.01) [C07C 231/00 (2013.01)] 36 Claims
 
1. A method of producing a peptide compound in which a protecting group removable by a silylating agent is removed, the method comprising the step of contacting a starting peptide compound comprising natural amino acid residues and/or amino acid analog residues with the silylating agent in a solvent and thereby removing the protecting group from the starting peptide compound,
wherein the silylating agent is prepared by:
(i) mixing a silyl compound with an electrophilic species scavenger, or
(ii) mixing an acid with a silyl-containing electrophilic species scavenger,
wherein the starting peptide compound comprises at least one protecting group removable by the silylating agent, and
wherein the starting peptide compound comprises at least one N-alkylated amino acid residue;
wherein the electrophilic species scavenger in (i) has a formula of formula (11) as defined below; and
wherein the silyl-containing electrophilic species scavenger in (ii) is a compound having a formula of formula (11) as defined below, provided that the compound has a silyl group:

OG Complex Work Unit Chemistry
wherein in formula 11,
RB is a substituted silyl group and RC is a substituted silyl group, or
RB and RC, together with the nitrogen atom and oxygen atom to which they are attached, form a 5- to 7-membered ring; and
RD is optionally substituted methylene.