CARBOHYDRATE CONJUGATED RNA AGENTS AND PROCESS FOR THEIR PREPARATION

1 . A compound of formula (A)

wherein

each occurrence of X is hydrogen or a hydroxy protecting group;

each occurrence of Y is an amine protecting group, (e.g., acetyl);

n is 0-20;

each occurrence of q, r and s is independently 1-7;

L is a linking group; and

R 1 is an iRNA agent;

wherein the compound of formula (A) is free or substantially free of one or more of

(i) metal impurities,

(ii) each of the following two urea side products

 and

(iii) each of the following saccharide compounds

2 . The compound according to claim 1 , wherein the compound of formula (A) contains no more than 0.5% of any individual urea side product or saccharide compound.

3 . The compound according to claim 1 , wherein the compound of formula (A) contains no more than 0.2% of any individual urea side product or saccharide compound.

4 . The compound according to claim 1 , wherein the compound of formula (A) contains no more than 1000 ppm of any individual metal.

5 . The compound according to claim 1 , wherein the compound of formula (A) contains no more than 100 ppm of any individual metal.

6 . The compound according to claim 1 , wherein the compound of formula (A) contains no more than 10 ppm of any individual metal.

7 . The compound according to claim 1 , wherein the compound of formula (A) contains no more than 1 ppm of any individual metal.

8 - 21 . (canceled)

22 . A process for preparing a compound of formula (I):

wherein

X is a hydroxyl protecting group;

Y is an amine protecting group;

Prt is a hydroxyl protecting group;

n is 0-15;

q, r and s are each, independently, 1-7; and

is a solid support;

said process comprising

(1) treating a compound of formula II:

with a compound of formula III:

in the presence of a base to afford a compound of formula (IV):

wherein Z is an acid protecting group;

(2) deprotecting Z in the compound of formula (IV), followed by coupling with a hydroxyl proline of formula (V):

(3) coupling the product of step (2) with succinic anhydride; and

(4) coupling the product of step (3) to a solid support to afford a compound of formula (I).

23 . The process of claim 22 , wherein X is Bz or Ac.

24 . The process of claim 22 , wherein Y is Ac.

25 . The process of claim 22 , wherein n is 7; and q, r, and s are each 1.

26 . The process of claim 22 , wherein Prt is a 4,4′-Dimethoxytrityl protecting group.

27 . A compound selected from

(i) a compound of formula (VIII):

wherein

A is a C 6 -C 14 alkylene linker,

each R is, independently, an acid protecting group, and

R x is an acid protecting group;

(ii) a compound of formula (XII):

wherein

Z is an acid protecting group,

n is 0-20,

each occurrence of q, r and s is independently 1-7, and

P is an amino protecting group with a sulfonic acid;

(iii) a compound of formula (II):

wherein

Z is an acid protecting group,

n is 0-20, and

each occurrence of q, r and s is independently 1-7; and

(iv) a compound of formula (XIII):

wherein

X is a hydroxyl protecting group,

Y is an amine protecting group,

Prt is a hydroxyl protecting group,

n is 0-15, and

q, r and s are each, independently, 1-7.

28 . The compound of claim 27 , wherein the compound is a compound of formula (VIII):

wherein

A is a C 6 -C 14 alkylene linker,

each R is, independently, an acid protecting group, and

R x is an acid protecting group.

29 . The compound of claim 27 , wherein the compound is a compound of formula (XII):

wherein

Z is an acid protecting group,

n is 0-20,

each occurrence of q, r and s is independently 1-7, and

P is an amino protecting group with a sulfonic acid.

30 . The compound of claim 27 , wherein the compound is a compound of formula (II):

wherein

Z is an acid protecting group,

n is 0-20, and

each occurrence of q, r and s is independently 1-7.

31 . The compound of claim 27 , wherein the compound is a compound of formula (XIII):

wherein

X is a hydroxyl protecting group,

Y is an amine protecting group,

Prt is a hydroxyl protecting group,

n is 0-15, and

q, r and s are each, independently, 1-7.