Methods for making oxetan-3-ylmethanamines

Patent metadata

Field	Value
Publication number	US-9376409-B2
Application number	US-201314399343-A
Country	US
Kind code	B2
Filing date	May 1, 2013
Priority date	May 9, 2012
Publication date	Jun 28, 2016
Grant date	Jun 28, 2016

Abstract

This invention relates to methods for making oxetan-3-ylmethanamines having the formula (I) wherein R1? and R2? are as defined herein. The methods of the invention provide the compounds of formula (I) in high yields and under conditions amenable for large-scale commercial production.

First claim

What is claimed is:

1. A method of making the compound of formula (I):

the method comprising the following steps:
1) reacting the compound of formula (V):

with a compound of formula (VI):
H—N(R 3 ) 2   (VI)

and a compound of formula (VII):

followed by reaction with acetic acid to provide the compound of formula (IV):

2) reacting the compound of formula (IV) from step 1) above with a reducing reagent to provide the compound of formula (III):

3) reacting the compound of formula (III) from step 2) above with an arylsulfonyl chloride and a deprotonating reagent to provide the compound of formula (II);

and 4) reacting the compound of formula (II) from step 3) above with hydrogen gas in the presence of a transition metal catalyst to provide the compound of formula (I),
wherein:
R 1 is selected from hydrogen, —(C 1 -C 6 )alkyl, —CF 3 , —(C 3 -C 6 )carbocyclyl, and phenyl;
R 2 is selected from hydrogen, —(C 1 -C 6 )alkyl, —CF 3 , —(C 3 -C 6 )carbocyclyl, and phenyl;
wherein at least one of R 1 and R 2 is hydrogen; and
each R 3 is independently selected from phenylmethyl, 4-methoxyphenylmethyl, 1-naphthylmethyl, and diphenylmethyl.

2. A method of making a compound of formula (I):

the process comprising:
reacting a compound of formula (II):

with hydrogen gas in the presence of a transition metal catalyst to provide the compound of formula (I);
wherein:
R 1 is selected from hydrogen, —(C 1 -C 6 )alkyl, —CF 3 , —(C 3 -C 6 )carbocyclyl, and phenyl;
R 2 is selected from hydrogen, —(C 1 -C 6 )alkyl, —CF 3 , —(C 3 -C 6 )carbocyclyl, and phenyl;
wherein at least one of R 1 and R 2 is hydrogen; and
each R 3 is independently selected from phenylmethyl, 4-methoxyphenylmethyl, 1-naphthylmethyl, and diphenylmethyl.

3. A method of making the compound of formula (II):

the process comprising:
reacting a compound of formula (III):

with an arylsulfonyl chloride and a deprotonating reagent to provide the compound of formula (II),
wherein:
R 1 is selected from hydrogen, —(C 1 -C 6 )alkyl, —CF 3 , —(C 3 -C 6 )carbocyclyl, and phenyl;
R 2 is selected from hydrogen, —(C 1 -C 6 )alkyl, —CF 3 , —(C 3 -C 6 )carbocyclyl, and phenyl;
wherein at least one of R 1 and R 2 is hydrogen; and
each R 3 is independently selected from phenylmethyl, 4-methoxyphenylmethyl, 1-naphthylmethyl, and diphenylmethyl.

4. A compound of formula (4):

and acid addition salts thereof.

Assignees

• Boehringer Ingelheim Int

Inventors

• Eriksson Magnus Carl Arne
• Kapadia Suresh R
• Reeves Jonathan Timothy
• Zeng Xingzhong

Classifications

• C07C229/24

  having more than one carboxyl group bound to the carbon skeleton, e.g. aspartic acid · CPC title

• C07C215/10

  with one amino group and at least two hydroxy groups bound to the carbon skeleton · CPC title

• C07C215/28

  and containing six-membered aromatic rings · CPC title

• C07C227/10

  with simultaneously increasing the number of carbon atoms in the carbon skeleton · CPC title

• C07D305/06 Primary

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring atoms · CPC title