Processes for preparing oligomers

1. A process for preparing an oligomeric compound of Formula (A):

wherein n is an integer from 10 to 40, and each R 2 is, independently for each occurrence, selected from the group consisting of:

wherein the process comprises the sequential steps of:

(a) contacting a compound of Formula (A1):

wherein R 1 is a support-medium and R 3 is selected from the group consisting of trityl, monomethoxytrityl, dimethoxytrityl and trimethoxytrityl;

with a deblocking agent to form the compound of Formula (II):

wherein R 1 is a support-medium;

(b) contacting the compound of Formula (II) with a compound of Formula (A2):

wherein R 3 is selected from the group consisting of trityl, monomethoxytrityl, dimethoxytrityl and trimethoxytrityl;

to form a compound of Formula (A3):

wherein R 1 is a support-medium, and R 3 is selected from the group consisting of trityl, monomethoxytrityl, dimethoxytrityl and trimethoxytrityl;

(c) contacting the compound of Formula (A3) with a deblocking agent to form a compound of Formula (IV):

wherein R 1 is a support-medium;

(d) contacting the compound of Formula (IV) with a compound of Formula (A4):

wherein R 3 is selected from the group consisting of trityl, monomethoxytrityl, dimethoxytrityl and trimethoxytrityl, and R 4 is selected from the group consisting of:

to form a compound of Formula (A5):

wherein R 1 is a support-medium, R 3 is selected from the group consisting of trityl, monomethoxytrityl, dimethoxytrityl and trimethoxytrityl, and

R 4 is selected from:

(e) performing n−1 iterations of the sequential steps of:

(e1) contacting the product formed by the immediately prior step with a deblocking agent; and

(e2) contacting the compound formed by the immediately prior step with a compound of Formula (A8):

wherein R 3 is selected from the group consisting of trityl, monomethoxytrityl, dimethoxytrityl and trimethoxytrityl, and R 4 is, independently for each compound of Formula (A8), selected from the group consisting of:

to form a compound of Formula (A9):

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 for each occurrence, selected from the group consisting of:

and

(f) contacting the compound of Formula (A9) with a deblocking agent to form a compound of Formula (A10):

wherein n is an integer from 10 to 40, R 1 is a support-medium, and R 4 is, independently for each occurrence, selected from the group consisting of:

(g) contacting the compound of Formula (A10) with a cleaving agent to form a compound of Formula (A11):

wherein n is an integer from 10 to 40, and R 4 is, independently for each occurrence, selected from the group consisting of:

and

(h) contacting the compound of Formula (A11) with a deprotecting agent to form the oligomeric compound of Formula (A).

2. The process of claim 1 , wherein step (d) or step (e2) further comprises contacting the compound of Formula (IV) or the compound formed by the immediately prior step, respectively, with a capping agent.

3. The process of claim 1 , wherein the deblocking agent used in each step is a solution comprising a halogenated acid.

4. The process of claim 1 , wherein the deblocking agent used in each step is cyanoacetic acid.

5. The process of claim 3 , wherein the halogenated acid is selected from the group consisting of chloroacetic acid, dichloroacetic acid, trichloroacetic acid, fluoroacetic acid, difluoroacetic acid, and trifluoroacetic acid.

6. The process of claim 1 , wherein at least one of steps (a), (c), (e1), and (f) further comprises the step of contacting the deblocked compound of each step with a neutralization agent.

7. The process of claim 1 , wherein each of steps (a), (c), (e1), and (f) further comprises the step of contacting the deblocked compound of each step with a neutralization agent.

8. The process of claim 6 , wherein the neutralization agent is a monoalkyl, dialkyl, or trialkyl amine.

9. The process of claim 1 , wherein the capping agent is an acid anhydride.

10. The process of claim 1 , wherein the compounds of Formula (A4) and Formula (A8) are each, independently, in a solution comprising ethylmorpholine and dimethylimidazolidinone.

11. The process of claim 1 , wherein the cleavage agent comprises dithiothreitol and 1,8-diazabicyclo[5.4.0]undec-7-ene.

12. The process of claim 1 , wherein the deprotecting agent comprises NH 3 .

13. The process of claim 1 , wherein the support-medium comprises polystyrene with 1% crosslinked divinylbenzene.

14. The process of claim 1 , wherein the compound of Formula (A4) is of Formula (A4a):

wherein:

R 3 is selected from the group consisting of trityl, monomethoxytrityl, dimethoxytrityl and trimethoxytrityl, and

R 4 is selected from:

15. The process of claim 1 , wherein the compound of Formula (A5) is of Formula (A5a):

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 selected from:

16. The process of claim 1 , wherein the compound of Formula (A8) is of Formula (A8a):

wherein:

R 3 is selected from the group consisting of trityl, monomethoxytrityl, dimethoxytrityl and trimethoxytrityl, and

R 4 is, independently at each occurrence of the compound of Formula (A8a), selected from the group consisting of:

17. The process of claim 1 , wherein the compound of formula (A9) is of Formula (A9a):

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 for each occurrence, selected from the group consisting of:

18. The process of claim 1 , wherein the compound of Formula (A10) is of Formula (A10a):

wherein:

n is an integer from 10 to 40,

R 1 is a support-medium, and

R 4 is, independently for each occurrence, selected from the group consisting of:

19. The process of claim 1 , wherein the compound of Formula (A11) is of Formula (A11a):

wherein:

n is an integer from 10 to 40, and

R 4 is, independently for each occurrence, selected from the group consisting of:

20. 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:

21. A compound selected from:

wherein n is an integer from 10 to 40, R 1 is a support-medium, X is 0 or S, R 5 is —OCH 2 CH 2 CN or —CH 2 C(═O)OC(CH 3 ) 2 CH 2 CN, each A, independently at each occurrence, is selected from the group consisting of:

R 3 is selected from the group consisting of trityl, monomethoxytrityl, dimethoxytrityl and trimethoxytrityl, and R 4 is, independently for each occurrence, selected from the group consisting of:

22. A compound selected from:

or a pharmaceutically acceptable salt thereof,

wherein:

each R 1 is independently a support-medium; and

each R 3 is independently selected from the group consisting of hydrogen, trityl, monomethoxytrityl, dimethoxytrityl and trimethoxytrityl.