IP Library › Granted Patent US 7,304,158
Granted Patent B2
US 7,304,158 · App. 11/411,952 · Granted Dec 4, 2007

Method for making 2-(7-chloro-1,8-naphthyridine-2-yl)-3-(5-methyl-2-oxo-hexyl)-1-isoindolinone)

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Quick Facts
Patent No.
US 7,304,158
App. No.
11/411,952
Granted
Dec 4, 2007
Kind
B2
Abstract

The present invention relates to methods for making racemic 2-(7-chloro -1,8-naphthyridin-2-yl)-3-(5-methyl-2-oxohexyl)-1-isoindolinone and (+)-2-(7 -chloro-1,8-naphthyridine-2-yl)-3-(5-methyl-2-oxo-hexyl)-1-isoindolinone.

Claims (18)

1. A method of making 2-amino-7-hydroxy-1,8-naphthyridine sulfuric acid salt, the method comprising the steps of

(a) dissolving 2,6-diaminopyridine in sulfuric acid to form a solution; and

(b) adding malic acid to the solution to obtain 2-amino-7-hydroxy-1,8-naphthyridine sulfuric acid salt.

2. A method of making racemic 2-(7-chloro-1,8-naphthyridin-2-yl)-3-(5-methyl-2-oxohexyl)-1-isoindolinone, the method comprising the steps of:

a) reacting 2-amino-7-hydroxy-1,8-naphthyridine sulfuric acid salt with a phthalyl reactant in a solvent to form phthalimidyl naphthyridine 2

b) reacting phthalimidyl naphthyridine 2 with a chlorinating agent to form chloride 3

c) reacting chloride 3 with a reducing agent to form hydroxyindolinone 4

d) reacting hydroxyindolinone 4 with a 5-methyl-2-oxo-hexyl triphenyiphosphonium halide to form racemic 2-(7-chloro-1,8-naphthyridin-2-yl)-3-(5-methyl-2-oxohexyl)-1-isoindolinone.

3. The method of claim 2 wherein in step a the phthalyl reactant is phthalic anhydride; in step b the chlorinating agent is phosphorus oxychloride; in step c the reducing agent is potassium borohydride; and in step d the 5-methyl-2-oxo-hexyl derivative is [(5-methyl-2-oxo)-hexyl]triphenyiphosphonium bromide.

4. A method of making racemic 2-(7-chloro-1,8-naphthyridin-2-yl)-3-(5-methyl-2-oxohexyl)-1-isoindolinone, the method comprising the steps of:

a) reacting phthalimidyl naphthyridine 2

with a chlorinating agent to form chloride 3

b) reacting chloride 3 with a reducing agent to form hydroxyindolinone 4

c) reacting hydroxyindolinone 4 with a 5-methyl-2-oxo-hexyltriphenylphosphonium halide to form racemic 2-(7-chloro-1,8-naphthyridin-2-yl)-3-(5-methyl-2-oxohexyl)-1-isoindolinone.

5. A method of making racemic 2-(7-chloro-1,8-naphthyridin-2-yl)-3-(5-methyl-2-oxohexyl)-1-isoindolinone, the method comprising the steps of:

a) reacting chloride 3

with a reducing agent to form hydroxyindolinone 4

b) reacting hydroxyindolinone 4 with a 5-methyl-2-oxo-hexyltriphenylphosphonium halide to form racemic 2-(7-chloro-1,8-naphthyridin-2-yl)-3-(5-methyl-2-oxohexyl)-1-isoindolinone.

Assignments (13)
RELEASE OF SECURITY INTEREST Recorded Apr 26, 2024
From: WILMINGTON TRUST, NATIONAL ASSOCIATION
To: ACTIENT PHARMACEUTICALS LLC; ASTORA WOMEN’S HEALTH HOLDINGS, LLC; ASTORA WOMEN’S HEALTH LLC; AUXILIUM PHARMACEUTICALS, LLC; AUXILIUM US HOLDINGS, LLC; BIOSPECIFICS TECHNOLOGIES CORP.; BIOSPECIFICS TECHNOLOGIES LLC; DAVA INTERNATIONAL, LLC; DAVA PHARMACEUTICALS, LLC; ENDO GENERIC HOLDINGS, INC. (FORMERLY KNOWN AS PAR PHARMACEUTICALS COMPANIES, INC.); ENDO PHARMACEUTICALS INC.; ENDO PHARMACEUTICALS SOLUTIONS INC. (FORMERLY KNOWN AS INDEVUS PHARMACEUTICALS, INC.); GENERICS BIDCO I, LLC; GENERICS INTERNATIONAL (US), INC.; PAR PHARMACEUTICAL, INC.; PAR STERILE PRODUCTS, LLC (FORMERLY KNOWN AS JHP PHARMACEUTICALS, LLC); QUARTZ SPECIALTY PHARMACEUTICALS, LLC; SLATE PHARMACEUTICALS, LLC; VINTAGE PHARMACEUTICALS, LLC
Reel/Frame 067240/0001 →
SECURITY INTEREST Recorded Jun 8, 2017
From: ENDO PHARMACEUTICALS SOLUTIONS INC.
To: WILMINGTON TRUST, NATIONAL ASSOCIATION, AS COLLATERAL TRUSTEE
Reel/Frame 042743/0001 →
RELEASE OF SECURITY INTEREST Recorded Apr 28, 2017
From: DEUTSCHE BANK AG NEW YORK BRANCH
To: ENDO PHARMACEUTICALS, INC.; ENDO PHARMACEUTICALS SOLUTIONS, INC.; ASTORA WOMEN'S HEALTH HOLDINGS, LLC
Reel/Frame 042362/0001 →
GRANT OF SECURITY INTEREST IN PATENTS Recorded Mar 20, 2014
From: ENDO PHARMACEUTICALS SOLUTIONS, INC.; ENDO PHARMACEUTICALS, INC.; AMS RESEARCH CORPORATION; AMERICAN MEDICAL SYSTEMS, INC.; LASERSCOPE
To: DEUTSCHE BANK AG NEW YORK BRANCH, AS COLLATERAL AGENT
Reel/Frame 032491/0440 →
RELEASE OF PATENT SECURITY INTEREST Recorded Mar 3, 2014
From: MORGAN STANLEY SENIOR FUNDING, INC., AS ADMINISTRATIVE AGENT
To: ENDO PHARMACEUTICALS SOLUTIONS INC.
Reel/Frame 032380/0226 →
RELEASE OF SECURITY INTEREST RECORDED AT REEL/FRAME 25434/842 Recorded Jul 11, 2011
From: JPMORGAN CHASE BANK N.A., AS ADMINISTRATIVE AGENT
To: ENDO PHARMACEUTICALS SOLUTIONS INC.
Reel/Frame 026571/0616 →
SECURITY AGREEMENT Recorded Jul 7, 2011
From: ENDO PHARMACEUTICALS SOLUTIONS INC.
To: MORGAN STANLEY SENIOR FUNDING, INC., AS ADMINISTRATIVE AGENT
Reel/Frame 026557/0373 →
RELEASE OF PATENT SECURITY INTEREST RECORDED AT REEL/FRAME 23390/220 Recorded Dec 3, 2010
From: JPMORGAN CHASE BANK, N.A., AS ADMINISTRATIVE AGENT
To: ENDO PHARMACEUTICALS SOLUTIONS INC.
Reel/Frame 025441/0710 →
SECURITY AGREEMENT Recorded Dec 1, 2010
From: ENDO PHARMACEUTICALS SOLUTIONS INC.
To: JPMORGAN CHASE BANK, N.A., AS ADMINISTRATIVE AGENT
Reel/Frame 025434/0842 →
SECURITY AGREEMENT Recorded Oct 19, 2009
From: ENDO PHARMACEUTICALS SOLUTIONS INC.
To: JPMORGAN CHASE BANK, N.A., AS ADMINISTRATIVE AGENT
Reel/Frame 023390/0220 →
CHANGE OF NAME Recorded Oct 2, 2009
From: INDEVUS PHARMACEUTICALS INC.
To: ENDO PHARMACEUTICALS SOLUTIONS INC.
Reel/Frame 023312/0681 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 27, 2006
From: WARNER LAMBERT COMPANY LLC (FORMERLY KNOWN AS WARNER-LAMBERT COMPANY)
To: INDEVUS PHARMACEUTICALS, INC.
Reel/Frame 019931/0393 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 27, 2006
From: JENNINGS, SANDRA MARIE; STUK, TIMOTHY LEE
To: WARNER-LAMBERT COMPANY
Reel/Frame 017834/0508 →