IP Library Granted Patent US 8,354,556
Granted Patent B2
US 8,354,556 · App. 12/908,977 · Granted Jan 15, 2013

Processes for preparing a polymeric compound

Inventors: Robert W. Kavash (Radnor, PA); Haizhong Tang (Radnor, PA); Carol Mulrooney (Radnor, PA); Dahui Liu (Radnor, PA)
Assignee: PolyMedix, Inc.
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Quick Facts
Patent No.
US 8,354,556
App. No.
12/908,977
Granted
Jan 15, 2013
Kind
B2
Abstract

The present invention provides methods for preparing a polymeric compound of Formula I: or pharmaceutically acceptable salt thereof. The present invention also provides useful intermediates for preparing the compound of Formula I or pharmaceutically acceptable salt thereof.

Claims (94)

1. A method for preparing a compound of Formula I:

or pharmaceutically acceptable salt thereof, comprising:

a) removing the Cbz groups from a compound of Formula II:

or pharmaceutically acceptable salt thereof, under a hydrogenation/hydrogenolysis condition to form the compound of Formula I, or pharmaceutically acceptable salt thereof; and

b) optionally isolating the compound of Formula I, or pharmaceutically acceptable salt thereof.

2. The method of claim 1 further comprising:

c) removing the Boc group from a compound of Formula III:

or pharmaceutically acceptable salt thereof, in the presence of an acid to form the compound of Formula II, or pharmaceutically acceptable salt thereof.

3. The method of claim 2 further comprising:

d) reacting a compound of Formula IV:

or pharmaceutically acceptable salt thereof, with a compound of Formula V:

or pharmaceutically acceptable salt thereof, in the presence of a coupling reagent and an organic base to form the compound of Formula III, or pharmaceutically acceptable salt thereof.

4. The method of claim 3 further comprising:

e) reacting a compound of Formula IV:

or pharmaceutically acceptable salt thereof, with ammonia or an ammonia producing reagent, in the presence of an activating reagent and an organic base to form a compound of Formula VI:

or pharmaceutically acceptable salt thereof; and

f) removing the Boc group from the compound of Formula VI, or pharmaceutically acceptable salt thereof, in the presence of an acid to form the compound of Formula V, or pharmaceutically acceptable salt thereof.

5. The method of claim 4 further comprising:

g) hydrolyzing a compound of Formula VII:

or pharmaceutically acceptable salt thereof, in the presence of a base to form the compound of Formula IV.

6. The method of claim 5 further comprising:

h) reacting a compound of Formula VIII:

or pharmaceutically acceptable salt thereof, with a compound of Formula IX:

or pharmaceutically acceptable salt thereof, in the presence of a coupling reagent and an organic base to form the compound of Formula VII, or pharmaceutically acceptable salt thereof.

7. The method of claim 6 further comprising:

i) hydrolyzing a compound of Formula X:

or pharmaceutically acceptable salt thereof, in the presence of a base to form the compound of Formula IX; and

j) removing the Boc group from a compound of Formula X, or pharmaceutically acceptable salt thereof, in the presence of an acid to form the compound of Formula VIII, or pharmaceutically acceptable salt thereof.

8. The method of claim 7 further comprising:

k) reacting a compound of Formula XI:

or pharmaceutically acceptable salt thereof, with a compound of Formula XII:

or pharmaceutically acceptable salt thereof, in the presence of a coupling reagent and an organic base to form the compound of Formula X, or pharmaceutically acceptable salt thereof.

9. A method for preparing a compound of formula I:

or pharmaceutically acceptable salt thereof, comprising:

a1) removing the Cbz groups from a compound of Formula II-1:

or pharmaceutically acceptable salt thereof, under a hydrogenation/hydrogenolysis condition to form the compound of Formula I, or pharmaceutically acceptable salt thereof; and

b1) optionally isolating the compound of Formula I, or pharmaceutically acceptable salt thereof.

10. The method of claim 9 further comprising:

c1) reacting a compound of Formula III-1:

or pharmaceutically acceptable salt thereof, with a compound of Formula IV-1:

or pharmaceutically acceptable salt thereof, in the presence of a coupling reagent and an organic base to form the compound of Formula II-1, or pharmaceutically acceptable salt thereof.

11. The method of claim 10 further comprising:

d1) reacting a compound of Formula VI-1:

or pharmaceutically acceptable salt thereof, with a compound of Formula VII-1:

or pharmaceutically acceptable salt thereof, in the presence of a coupling reagent and an organic base to form a compound of Formula V-1:

or pharmaceutically acceptable salt thereof; and

e1) removing the Boc group from the compound of Formula V-1, or pharmaceutically acceptable salt thereof, in the presence of an acid to form the compound of Formula III-1, or pharmaceutically acceptable salt thereof.

12. The method of claim 10 further comprising:

f1) reacting a compound of Formula VIII-1:

or pharmaceutically acceptable salt thereof, with a compound of Formula VII-1:

or pharmaceutically acceptable salt thereof, in the presence of a coupling reagent and an organic base to form a compound of Formula IX-1:

or pharmaceutically acceptable salt thereof; and

g1) removing the Boc group from the compound of Formula IX-1, or pharmaceutically acceptable salt thereof, in the presence of an acid to form the compound of Formula VI-1, or pharmaceutically acceptable salt thereof.

13. The method of claim 12 further comprising:

h1) reacting a compound of Formula XI-1:

or pharmaceutically acceptable salt thereof, with a compound of Formula XII-1:

or pharmaceutically acceptable salt thereof, optionally in the presence of an organic base to form a compound of Formula X-1:

or pharmaceutically acceptable salt thereof; and

i1) removing the Boc group from the compound of Formula X-1 or pharmaceutically acceptable salt thereof, in the presence of an acid to form the compound of Formula VIII-1, or pharmaceutically acceptable salt thereof.

14. The method of claim 12 further comprising:

j1) reacting a compound of Formula XI-1:

or pharmaceutically acceptable salt thereof, with a compound of Formula XIII-1:

or pharmaceutically acceptable salt thereof, to form the compound of Formula VII-1, or pharmaceutically acceptable salt thereof.

15. The method of claim 14 further comprising:

k1) reacting a compound of Formula XIV-1:

or pharmaceutically acceptable salt thereof, with a compound of Formula XIII-1:

or pharmaceutically acceptable salt thereof, to form the compound of Formula IV-1, or pharmaceutically acceptable salt thereof.

16. The method of claim 9 further comprising:

c2) reacting a compound of Formula III-2:

or pharmaceutically acceptable salt thereof, with a compound of Formula IV-2:

or pharmaceutically acceptable salt thereof, in the presence of a coupling reagent and an organic base to form the compound of Formula II-1, or pharmaceutically acceptable salt thereof.

17. The method of claim 16 further comprising:

d2) removing the Boc group from a compound of Formula V-2:

or pharmaceutically acceptable salt thereof, under an acidic condition to form the compound of Formula III-2, or pharmaceutically acceptable salt thereof.

18. The method of claim 17 , further comprising:

e2) reacting a compound of Formula VI-2:

or pharmaceutically acceptable salt thereof, with a compound of Formula VII-2:

or pharmaceutically acceptable salt thereof, in the presence of a coupling reagent and an organic base to form the compound of Formula V-2, or pharmaceutically acceptable salt thereof.

19. The method of claim 18 further comprising:

f2) removing the Boc group from a compound of Formula VIII-2:

or pharmaceutically acceptable salt thereof, under an acidic condition to form the compound of Formula VI-2, or pharmaceutically acceptable salt thereof.

20. The method of claim 19 further comprising:

g2) reacting a compound of Formula IX-2:

or pharmaceutically acceptable salt thereof, with a compound of Formula VII-2:

or pharmaceutically acceptable salt thereof, in the presence of a coupling reagent and an organic base to form the compound of Formula VIII-2, or pharmaceutically acceptable salt thereof.

21. The method of claim 20 further comprising:

h2) removing the Boc group from a compound of Formula X-2:

or pharmaceutically acceptable salt thereof, under an acidic condition to form the compound of Formula IX-2, or pharmaceutically acceptable salt thereof.

22. The method of claim 21 further comprising:

i2) reacting a compound of Formula VII-2:

or pharmaceutically acceptable salt thereof, with a compound of Formula XI-2:

or pharmaceutically acceptable salt thereof, in the presence of a coupling reagent and an organic base to form the compound of Formula X-2, or pharmaceutically acceptable salt thereof.

23. A compound chosen from:

or pharmaceutically acceptable salt thereof.

Assignments (3)
BANKRUPTCY COURT ORDER/ASSET PURCHASE AGREEMENT Recorded Nov 12, 2013
From: POLYMEDIX, INC.
To: CELLCEUTIX CORPORATION
Reel/Frame 031626/0106 →
INTELLECTUAL PROPERTY SECURITY AGREEMENT Recorded Jan 17, 2013
From: POLYMEDIX, INC.; POLYMEDIX PHARMACEUTICALS, INC.
To: MIDCAP FINANCIAL SBIC, LP, AS ADMINISTRATIVE AGENT
Reel/Frame 029660/0322 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 3, 2011
From: KAVASH, ROBERT W.; TANG, HAIZHONG; MULROONEY, CAROL; LIU, DAHUI
To: POLYMEDIX, INC.
Reel/Frame 025572/0292 →
Continuity (2)
Provisional Application 61253975 · Oct 22, 2009
Related Publication 20110098498A1 · Apr 28, 2011