IP Library › Granted Patent US 8,183,401
Granted Patent B2
US 8,183,401 · App. 10/586,237 · Granted May 22, 2012

Exemestane and its intermediates and methods of making the same

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Quick Facts
Patent No.
US 8,183,401
App. No.
10/586,237
Granted
May 22, 2012
Kind
B2
Abstract

A method is provided for preparing an aromatase inhibitor of formula (I) wherein each of R 1 , R 2 , R 3 , R 4 , independently, is hydrogen, halogen or C 1 -C 6 alkyl. In one form, the aromatase inhibitor is exemestane wherein each of R 1 , R 2 , R 3 , R 4 is hydrogen. In the method, a compound of formula (II) wherein R 1 , R 2 , R 3 , R 4 are as defined above and R is alkylene, is reacted with a deprotonating agent and a compound of the formula R 5 SO 2 X wherein R 5 is C 1 -C 5 alkyl and X is halogen so as to obtain a compound of formula (III) wherein R 1 , R 2 , R 3 , R 4 , R 5 are as defined above. The compound of Formula (III) is then reacted with a base to form an aromatase inhibitor of formula (I).

Claims (44)

1. A method for preparing a compound of formula (I)

wherein each of R 1 , R 2 , R 3 , R 4 , independently, is hydrogen, halogen or C 1 -C 6 alkyl, the method comprising:

reacting a compound of formula (II)

wherein R 1 , R 2 , R 3 , R 4 are as defined above and R is alkylene, with a deprotonating agent and a compound of the formula R 5 SO 2 X wherein R 5 is C 1 -C 5 alkyl and X is halogen so as to obtain a compound of formula (III)

wherein R 1 , R 2 , R 3 , R 4 , R 5 are as defined above; and

reacting the compound of formula (III) with a base.

2. The method of claim 1 wherein:

wherein each of R 1 , R 2 , R 3 , R 4 is hydrogen.

3. The method of claim 1 wherein:

R is methylene.

4. The method of claim 1 wherein:

the deprotonating agent is an amine.

5. The method of claim 1 wherein:

the deprotonating agent is a tertiary amine.

6. The method of claim 1 wherein:

the deprotonating agent is a trialkyl amine.

7. The method of claim 1 wherein:

R 5 is methyl.

8. The method of claim 1 wherein:

R 5 is methyl and X is chlorine.

9. The method of claim 1 wherein:

wherein each of R 1 , R 2 , R 3 , R 4 is hydrogen,

R is methylene,

the deprotonating agent is a trialkyl amine,

R 5 is methyl, and

X is chlorine.

10. The method of claim 1 wherein:

the base is an alkali metal hydroxide.

11. The method of claim 1 wherein:

the base is potassium hydroxide.

12. The method of claim 1 wherein:

the compound of formula (III) is reacted with the base in a solvent.

13. The method of claim 1 wherein:

the solvent is an alkanol.

14. A method for preparing a compound of formula

the method comprising:

reacting a compound of formula (V)

with a deprotonating agent and a compound of the formula R 5 SO 2 X wherein R 5 is C 1 -C 5 alkyl and X is halogen so as to obtain a compound of formula (VI)

and then reacting the compound of formula (VI) with a base in a solvent.

15. The method of claim 14 wherein:

R 5 is methyl and X is chlorine.

16. The method of claim 15 wherein:

the base is an alkali metal hydroxide, and

the solvent is an alkanol.

Assignments (10)
ASSIGNMENT OF SECURITY INTEREST IN INTELLECTUAL PROPERTY, RECORDED ON SEPTEMBER 1, 2017, AT REEL/FRAME 043746/0621 Recorded Mar 17, 2025
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From: WILMINGTON TRUST, NATIONAL ASSOCIATION, AS COLLATERAL AGENT
To: CURIA WISCONSIN, INC.
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SECURITY INTEREST Recorded Sep 6, 2021
From: CURIA GLOBAL, INC. (FKA ALBANY MOLECULAR RESEARCH, INC.); CURIA MASSACHUSETTS, INC. (FKA AMRI BURLINGTON, INC.); CURIA WISCONSIN, INC. (FKA CEDARBURG PHARMACEUTICALS, INC.); CURIA INDIANA, LLC (FKA AMRI SSCI, LLC); CURIA NEW MEXICO, LLC (FKA OSO BIOPHARMACEUTICALS MANUFACTURING, LLC); CURIA IP HOLDINGS, LLC
To: WILMINGTON TRUST, NATIONAL ASSOCIATION, AS COLLATERAL AGENT
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RELEASE OF SECURITY INTEREST Recorded Oct 29, 2020
From: MORGAN STANLEY SENIOR FUNDING, INC., AS COLLATERAL AGENT
To: ALBANY MOLECULAR RESEARCH, INC.; AMRI BURLINGTON, INC.; CEDARBURG PHARMACEUTICALS, INC.; EUTICALS INC.; OSO BIOPHARMACEUTICALS MANUFACTURING, LLC
Reel/Frame 054252/0687 →
CORRECTIVE ASSIGNMENT TO CORRECT THE INCORRECT PATENT NO. 7541537 PREVIOUSLY RECORDED AT REEL: 034045 FRAME: 0951. ASSIGNOR(S) HEREBY CONFIRMS THE SECURITY INTEREST. Recorded Aug 14, 2018
From: ALBANY MOLECULAR RESEARCH, INC.; ALO ACQUISITION LLC; AMRI BURLINGTON, INC.; AMRI RENSSELAER, INC.; CEDARBURG PHARMACEUTICALS, INC.; OSO BIOPHARMACEUTICALS MANUFACTURING, LLC
To: BARCLAYS BANK PLC, AS THE COLLATERAL AGENT
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FIRST LIEN SECURITY AGREEMENT Recorded Sep 1, 2017
From: ALBANY MOLECULAR RESEARCH, INC.; AMRI BURLINGTON, INC.; CEDARBURG PHARMACEUTICALS, INC.; EUTICALS INC.; OSO BIOPHARMACEUTICALS MANUFACTURING, LLC-BY ITS SOLE MEMBER: ALO ACQUISITION LLC
To: BARCLAYS BANK, PLC AS COLLATERAL AGENT
Reel/Frame 043746/0621 →
SECOND LIEN SECURITY AGREEMENT Recorded Sep 1, 2017
From: ALBANY MOLECULAR RESEARCH, INC.; AMRI BURLINGTON, INC.; CEDARBURG PHARMACEUTICALS, INC.; EUTICALS INC.; OSO BIOPHARMACEUTICALS MANUFACTURING LLC-BY ITS SOLE MEMBER:ALO ACQUISITION LLC
To: MORGAN STANLEY SENIOR FUNDING, INC.
Reel/Frame 043746/0657 →
RELEASE OF SECURITY INTEREST Recorded Aug 31, 2017
From: BARCLAYS BANK PLC, AS COLLATERAL AGENT
To: ALBANY MOLECULAR RESEARCH, INC.; ALO ACQUISITION LLC; AMRI BURLINGTON, INC.; AMRI RENSSELAER, INC.; CEDARBURG PHARMACEUTICALS, INC.; OSO BIOPHARMACEUTICALS MANUFACTURING, LLC; AMRI SSCI, LLC; EUTICALS INC.
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SECURITY INTEREST Recorded Oct 24, 2014
From: ALBANY MOLECULAR RESEARCH, INC.; ALO ACQUISITION LLC; AMRI BURLINGTON, INC.; AMRI RENSSELAER, INC.; CEDARBURG PHARMACEUTICALS, INC.; OSO BIOPHARMACEUTICALS MANUFACTURING, LLC
To: BARCLAYS BANK PLC, AS THE COLLATERAL AGENT
Reel/Frame 034045/0951 →