Processes for preparing oligomers
Provided herein are processes for preparing an oligomer (e.g., a morpholino oligomer). The synthetic processes described herein may be advantageous to scaling up oligomer synthesis while maintaining overall yield and purity of a synthesized oligomer.
1. A compound of Formula (B1):
or a pharmaceutically acceptable salt thereof
wherein
R 11 is selected from the group consisting of halo, CN, and NO 2 ;
R 12 is C 1-6 -alkyl;
R 13 is H or C 1-6 -alkyl; and
R 14 is a first linker bound to a support-medium,
R 3 is selected from the group consisting of trityl, monomethoxytrityl, dimethoxytrityl and trimethoxytrityl.
2. The compound of claim 1 , wherein the compound of Formula (B1) is of Formula (I):
wherein R 1 is a support-medium.
3. A compound of Formula (II-B):
or a pharmaceutically acceptable salt thereof
wherein
R 11 is selected from the group consisting of halo, CN, and NO 2 ;
R 12 is C 1-6 -alkyl;
R 13 is H or C 1-6 -alkyl; and
R 14 is a first linker bound to a support-medium.
4. The compound of claim 3 , wherein the compound of Formula (II-B) is Formula (II):
wherein R 1 is a support-medium.
5. A compound of Formula (B3):
or a pharmaceutically acceptable salt thereof
wherein
w is selected from O or C;
t is 1, 2, 3, 4, or 5;
R 11 is selected from the group consisting of halo, CN, and NO 2 ;
R 12 is C 1-6 -alkyl;
R 13 is H or C 1-6 -alkyl;
R 14 is a first linker bound to a support-medium;
R 8 is selected from:
wherein R 4 is selected from the group consisting of:
and
R 3 is selected from the group consisting of trityl, monomethoxytrityl, dimethoxytrityl and trimethoxytrityl.
6. The compound of claim 5 , wherein the compound of Formula (B3) is of Formula (III):
wherein R 1 is a support-medium.
7. A compound selected from:
wherein:
n is an integer from 10 to 40;
R 1 is a support-medium;
R 3 is selected from the group consisting of trityl, monomethoxytrityl, dimethoxytrityl and trimethoxytrityl; and
R 4 is, independently at each occurrence, selected from the group consisting of:
8. A compound selected from:
wherein:
R 11 is selected from the group consisting of halo, CN, and NO 2 ;
R 12 is C 1-6 -alkyl;
R 13 is H or C 1-6 -alkyl;
R 14 is a first linker bound to a support-medium;
R 1 is selected from —O(C 1 -C 6 alkyl), halo, —O(C 1 -C 6 alkyl)-O(C 1 -C 6 alkyl), and —O(C 1 -C 6 alkyl)-C(O)—NH—C 1 -C 6 alkyl
R 2 is H or R 1 and R 2 join to form a cycloalkyl or heterocyclic ring having from 4 to 7 ring atoms optionally containing an oxygen;
R 5 , R 6 , and R 7 are each hydrogen, or R 5 and R 7 join to form a cycloalkyl ring having from 4 to 7 ring atoms and R 6 and R 7 join to for a cycloalkyl ring having from 3 to 4 ring atoms,
R 9 is —OCH 2 CH 2 CN or —CH 2 C(═O)OC(CH 3 ) 2 CH 2 CN;
R 4 is, independently at each occurrence, selected from the group consisting of:
R 8 is, independently at each occurrence, selected from the group consisting of H, trityl, monomethoxytrityl, dimethoxytrityl and trimethoxytrityl;
n is 10 to 40; and
X is O or S.