Substituted pyrazines and a process for producing the same

Patent metadata

Field	Value
Publication number	US-9346767-B2
Application number	US-201514734471-A
Country	US
Kind code	B2
Filing date	Jun 9, 2015
Priority date	Mar 8, 2011
Publication date	May 24, 2016
Grant date	May 24, 2016

Abstract

Described include (1) a substituted pyrazine compound of general formula (VIII):

and (2) a process for producing the substituted pyrazine compound of general formula (VIII), where R 1 is hydrogen, a halogen, a substituted or unsubstituted hydrocarbon group, or a substituted or unsubstituted heterocyclic group, and R 4 is a protecting group. The process comprises (1) the step of reacting 2-amino-3,5-dibromo-6-chloropyrazine with R 1 MgX and ZnCl 2 in the presence of a palladium catalyst to produce a compound of general formula (V); (2) the step of reacting the compound of general formula (V) with a compound of general formula (VI) to produce a compound of general formula (VII); and (3) the step of reacting the compound of formula (VII) with tributyl(vinyl)tin in the presence or a palladium catalyst to given the compound of general formula (VIII).

First claim

The invention claimed is:

1. A compound represented by formula (VIII):

wherein
R 1 is hydrogen; a halogen; an aryl which may optionally be substituted with at least one substituent selected from the group consisting of a halogen, hydroxy, an alkyl having 1 to 6 carbon atoms, an alkoxy having 1 to 6 carbon atoms, an amino and a dialkylamino having 1 to 6 carbon atoms; an arylalkyl which may optionally be substituted with at least one substituent selected from the group consisting of a halogen, hydroxy, an alkyl having 1 to 6 carbon atoms, an alkoxy having 1 to 6 carbon atoms, an amino and a dialkylamino having 1 to 6 carbon atoms; an arylalkenyl which may optionally be substituted with at least one substituent selected from the group consisting of a halogen, hydroxy, an alkyl having 1 to 6 carbon atoms, an alkoxy having 1 to 6 carbon atoms, an amino and a dialkylamino having 1 to 6 carbon atoms; an alkyl which may optionally be substituted with an alicyclic group; an alkenyl which may optionally be substituted with an alicyclic group; an alicyclic group; a heterocyclic group; or an alkynyl which may optionally be substituted with an alicyclic group, and
R 4 is a protecting group selected from the group consisting of methyl, methoxymethyl, tetrahydropyranyl, benzyl, 4-methoxybenzyl, tert-butyldimethylsilyl, trimethylsilyl, triethylsilyl, phenyldimethylsilyl, tert-butyldiphenylsilyl, and triisopropylsilyl.

2. The compound according to claim 1 , wherein the compound is:

3. A process for producing a compound represented by formula (VIII):

wherein R 1 is hydrogen; a halogen; an aryl which may optionally be substituted with at least one substituent selected from the group consisting of a halogen, hydroxy, an alkyl having 1 to 6 carbon atoms, an alkoxy having 1 to 6 carbon atoms, an amino and a dialkylamino having 1 to 6 carbon atoms; an arylalkyl which may optionally be substituted with at least one substituent selected from the group consisting of a halogen, hydroxy, an alkyl having 1 to 6 carbon atoms, an alkoxy having 1 to 6 carbon atoms, an amino and a dialkylamino having 1 to 6 carbon atoms; an arylalkenyl which may optionally be substituted with at least one substituent selected from the group consisting of a halogen, hydroxy, an alkyl having 1 to 6 carbon atoms, an alkoxy having 1 to 6 carbon atoms, an amino and a dialkylamino having 1 to 6 carbon atoms; an alkyl which may optionally be substituted with an alicyclic group; an alkenyl which may optionally be substituted with an alicyclic group; an alicyclic group; a heterocyclic group; or an alkynyl which may optionally be substituted with an alicyclic group, and
R 4 is a protecting group selected from the group consisting of methyl, methoxymethyl, tetrahydropyranyl, benzyl, 4-methoxybenzyl, tert-butyldimethylsilyl, trimethylsilyl, triethylsilyl, phenyldimethylsilyl, tert-butyldiphenylsilyl, and triisopropylsilyl,
which comprises:
(1) reacting 2-amino-3,5-dibromo-6-chloropyrazine with R 1 MgX and ZnCl 2 , wherein R 1 is the same as defined above and X is a halogen, in the presence of a palladium catalyst to give a compound represented by formula (V):

 wherein R 1 is the same as defined above;
(2) reacting the compound represented by formula (V) with a compound represented by formula (VI):

 wherein R 4 is the same as defined above, in the presence of a palladium catalyst and a base to give a compound represented by formula (VII):

 wherein R 1 and R 4 are the same as defined above; and,
(3) reacting the compound represented by formula (VII) with tributyl(vinyl)tin in the presence of a palladium catalyst to give the compound represented by formula (VIII).

4. The process according to claim 3 , wherein R 1 is selected from the group consisting of phenyl, p-hydroxyphenyl, benzyl, α-hydroxybenzyl, phenylethyl, phenylvinyl, cyclohexyl, cyclohexylmethyl, cyclohexylethyl, methyl, ethyl, propyl, 2-methylpropyl, 2-methylpropenyl, adamantylmethyl, cyclopentylmethyl, and thiophen-2-yl.

5. The process according to claim 3 , wherein R 1 is benzyl.

6. The process according to claim 3 , wherein R 4 is methyl.

Assignees

• Jnc Corp
• Nat Univ Corp Tokyo Med & Dent

Inventors

• Inouye Satoshi
• Miura Yuiko
• Yoshida Suguru
• Hosoya Takamitsu

Classifications

• C07D487/04

  Ortho-condensed systems · CPC title

• C07D241/44 Primary

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring · CPC title

• C07D241/20

  Nitrogen atoms (nitro radicals C07D241/16) · CPC title

• C07D241/54

  Nitrogen atoms · CPC title

• C07D241/38 Primary

  with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms · CPC title