Process for making pyrimidine derivatives

Details Process for making pyrimidine derivatives Process for making pyrimidine derivatives

2000-03-16

2001-08-14

Ford, John M. (Department: 1624)

Organic compounds -- part of the class 532-570 series

Organic compounds

Nitrogen attached directly or indirectly to the purine ring...

C544S320000, C544S298000

Reexamination Certificate

active

06274734

ABSTRACT:

BACKGROUND OF THE INVENTION
The present invention provides a new process for the preparation of pyrimidine derivatives.
SUMMARY OF THE INVENTION
The subject process for manufacturing a compound of the formula:
R
1
, R
2
, R
3
each independently is hydrogen, C
1-7
-alkyl, or C
1-7
-alkoxy, and
A is —CN,
which comprises reacting a compound of the formula:
 wherein R
1
, R
2
and R
3
are as above and X is chlorine, with an alkali cyanide in the presence of 1-azabicyclo[2,2,2]octane or 1,4-diazabicyclo[2,2,2]octane.
Of particular concern is a process for manufacturing 2-cyanopyrimidine, which comprises reacting 2-chloropyrimidine with an alkali cyanide in the presence of 1-azabicyclo-[2,2,2]octane or 1,4-diazabicyclo[2,2,2]octane.
Another particularly useful process is for manufacturing 4-tertbutyl-N-6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-(pyrimidin-2-yl)-pyrimidin-4-yl-benzenesulphonamide, This process comprises manufacturing 2-cyanopyrimidine by reacting 2-chloropyrimidine with an alkali cyanide in the presence of 1-azabicyclo[2,2,2]octane or 1,4-diazabicyclo[2,2,2]octane. The 2-cyano pyrimidine is then converted by means of NH
3
/NH
4
Cl in a sodium methanolate/methanol solution into pyrimidin-2-carboxamidine hydrochloride. The pyrimidine-2-caroboxamidine hydrochloride is then converted in the presence of sodium methanolate with diethyl (o-methoxy-phenoxy-malonate) into rac-5-(2-methoxy-phenoxy)-2-pyrimidin-2-yl-tetrahydro-pyrimidin-4,6-dione. This product is then reacted with N,N-diisopropyl-N-ethylamine and phosphorus pentachloride to give 4,6-dichloro-5-(2-methoxy-phenoxy)-2,2′-bipyrimidine. This in turn is reacted with p-tert.butylbenzenesulphonamide to give 4-tert.butyl-N-6-chloro-5-[2-(2-methoxy-phenoxy)-2-(pyrimidin-2-yl)-pyrimidin-4-yl]-benzenesulphonamide which is reacted with sodium ethylene glycolate to give 4-tert.butyl-N-6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-(pyrimidin-2-yl)-pyrimidin-4-yl-benzenesulphonamide.
Intermediates in the above process include a compound of the formula:
wherein R
1
, R
2
, R
3
each independently is hydrogen, C
1-7
-alkyl, or C
1-7
-alkoxy, and salts thereof; and a compound of the formula:
wherein R
1
, R
2
, R
3
each independently is hydrogen, C
1-7
-alkyl, or C
1-7
-alkoxy, and salts thereof.


REFERENCES:
patent: 3178254 (1965-04-01), Hoelzle et al.

Affiliated with

Also associated with

Rating

Process for making pyrimidine derivatives does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Process for making pyrimidine derivatives, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for making pyrimidine derivatives will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2480213