IP Library › Granted Patent US 8,742,109
Granted Patent B2
US 8,742,109 · App. 13/620,391 · Granted Jun 3, 2014

Synthetic methods for spiro-oxindole compounds

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Quick Facts
Patent No.
US 8,742,109
App. No.
13/620,391
Granted
Jun 3, 2014
Kind
B2
Abstract

This invention is directed to methods of preparing certain spiro-oxindole derivatives, which are useful for the treatment and/or prevention of sodium channel-mediated diseases or conditions, such as pain.

Claims (23)

1. A method of preparing a compound of formula (II):

or a pharmaceutically acceptable salt thereof, as a single stereoisomer or enantiomer or a mixture thereof;

wherein the method comprises:

a) treating a compound of formula (14):

or a pharmaceutically acceptable salt thereof, with an alkylating agent under suitable conditions to form a compound of formula (15):

or a pharmaceutically acceptable salt thereof; and

b) treating the compound of formula (15), or a pharmaceutically acceptable salt thereof, with a compound of formula (16):

or a pharmaceutically acceptable salt thereof, under suitable conditions to provide the compound of formula (II), or a pharmaceutically acceptable salt thereof, as a single stereoisomer or enantiomer or a mixture thereof.

2. The method of claim 1 further comprising a preparation of the compound of formula (14), or a pharmaceutically acceptable salt thereof, wherein the method comprises treating a compound of formula (13):

or a pharmaceutically acceptable salt thereof, under suitable conditions to form the compound of formula (14), or a pharmaceutically acceptable salt thereof.

3. The method of claim 2 further comprising a preparation of the compound of formula (13), or a pharmaceutically acceptable salt thereof, wherein the method comprises:

c) reacting a compound of formula (12):

with a Grignard reagent of formula (3):

under suitable conditions to form an intermediate product; and

d) reacting the intermediate product of c) with a compound of formula (I):

or a pharmaceutically acceptable salt thereof, under suitable conditions to form the compound of formula (13), or a pharmaceutically acceptable salt thereof.

4. The method of claim 3 further comprising a preparation of the compound of formula (12), or a pharmaceutically acceptable salt thereof, wherein the method comprises treating a compound of formula (II):

with an oxidizing agent under suitable conditions to form the compound of formula (12), or a pharmaceutically acceptable salt thereof.

5. The method of claim 4 further comprising a preparation of the compound of formula (II), wherein the method comprises treating a compound of formula (10):

with a suitable alkylating reagent under suitable conditions to form the compound of formula (II).

6. The method of claim 1 further comprising resolving a compound of formula (II) under suitable conditions to yield a compound of formula (II-S):

or a pharmaceutically acceptable salt thereof; and a compound of formula (II-R):

or a pharmaceutically acceptable salt thereof.