Processes for making alkylated arylpiperazine and alkylated arylpiperidine compounds including novel intermediates

Patent metadata

Field	Value
Publication number	US-9957283-B1
Application number	US-201715784585-A
Country	US
Kind code	B1
Filing date	Oct 16, 2017
Priority date	Jun 16, 2014
Publication date	May 1, 2018
Grant date	May 1, 2018

Abstract

Novel processes, and intermediates, for making alkylated arylpiperazine and alkylated arylpiperidine compounds of the general formulas (I) and (VII), respectively

wherein, R 1 and R 2 are individually selected from hydrogen, alkyl, substituted or alkyl; n=0, 1, or 2; Y=NR 3 R 4 , OR 5 , or SR 5 , where R 3 and R 4 are individually selected from acyl or sulfonyl, and where R 5 is aryl or heteroaryl, or heterocyclic; and Ar is an aryl, heteroaryl, or heterocyclic compound.

First claim

What is claimed is:

1. A method of preparing

wherein
Y is selected from the group consisting of

and
Ar is selected from the group consisting of

provided that when Y is

then Ar is

or when Y is

then Ar is

or when Y is

then Ar is

comprising
(i) alkylating 1,3,2-dioxathiane 2,2-dioxide having the formula

with

in the presence of base selected from potassium carbonate, sodium carbonate, magnesium carbonate, calcium carbonate, potassium hydroxide, sodium hydroxide, magnesium hydroxide or calcium hydroxide, to form the corresponding alkylation compound of the formula

wherein Q is potassium, sodium, magnesium or calcium,
(ii) hydrolyzing the alkylation compound of step (i) with aqueous acid to obtain the corresponding hydroxyl compound of formula

wherein Y is selected from the group consisting of

(iii) converting the compound of formula

of step (ii) to the corresponding alkylating agent compound of formula

wherein LG is an aryl sulfonate or alkyl sulfonate, and
(iv) alkylating the compound of formula

of step (iii) with the compound of formula

wherein Ar is selected from the group consisting of

in the presence of base selected from potassium carbonate, sodium carbonate, magnesium carbonate, calcium carbonate, potassium hydroxide, sodium hydroxide, magnesium hydroxide or calcium hydroxide,
provided that when Y is

then Ar is

or when Y is

then Ar is

or when Y is

then Ar is

2. The process of claim 1 wherein the base of steps (i) and (iv) is potassium carbonate.

3. The process of claim 1 wherein LG is methylsulfonate.

4. The process of claim 1 wherein Y is

and Ar is

5. The process of claim 1 wherein Y is

and Ar is

6. The process of claim 1 wherein Y is

and Ar is

Assignees

• Johnson Matthey Plc

Inventors

• Coughlin Daniel J
• Wilt Jeremy C
• Gou Da-Ming
• Collier Steven

Classifications

• C07D241/04

  having no double bonds between ring members or between ring members and non-ring members · CPC title

• C07D417/08

  linked by a carbon chain containing alicyclic rings · CPC title

• C07D209/52

  condensed with a ring other than six-membered · CPC title

• C07D471/12

  in which the condensed system contains three hetero rings · CPC title

• C07D275/06

  with hetero atoms directly attached to the ring sulfur atom · CPC title