Method for preparation of 5-substituted pyrimidines

Patent metadata

Field	Value
Publication number	US-9169216-B2
Application number	US-201214006171-A
Country	US
Kind code	B2
Filing date	Mar 8, 2012
Priority date	Mar 22, 2011
Publication date	Oct 27, 2015
Grant date	Oct 27, 2015

Abstract

The present invention provides a method to prepare 5-substituted pyrimidines by reacting a 5-acylpyrimidine with a suitable nucleophile to afford a 5-methanolpyrimidine, such as flurprimidol.

First claim

What is claimed is:

1. A method for preparing a 5-acylpyrimidine comprising:
(a) reacting a pyrimidine of formula (II):

wherein X is halo or a sulfonate leaving group, and a compound of formula
(R 1 CH 2 )(Li + ) x (M ++ ) y (X − ) z   (V)

wherein R 1 is an organic group, M is a metal cation, each X is halo, and x, y and z are selected so that the net charge of the compound (V) is 0, wherein the coupling is carried out in the presence of an effective catalytic amount of a complexed metal, to yield a compound of formula VI;

and
(b) oxidizing the compound of formula (VI) to yield a 5-acylpyrimidine compound of formula (VII):

2. The method of claim 1 further comprising reacting the compound of formula VII with a solvate of the formula (Li(R 2 —ZnX)MgX 2 ) y .(.ether)) z wherein R 2 is an organic group and each X is halo, and x and y are selected so that the low-lying d-orbitals of the transition metal are filled, to yield a compound of formula (I):

3. The method of claim 1 wherein X is halo.

4. The method of claim 3 wherein X is Br or Cl.

5. The method of claim 1 wherein M ++ in compound (V) is Zn ++ or Mg ++ .

6. The method of claim 1 wherein R 1 is aryl or (substituted)aryl.

7. The method of claim 6 wherein R 1 is (substituted)phenyl.

8. The method of claim 1 wherein the metal in the complexed metal is palladium, nickel or iron.

9. The method of claim 8 wherein the metal is complexed with triphenyphosphine or acetylacetone.

10. The method of claim 9 wherein the catalyst is (Ph 3 P) 4 Pd, (PPh 3 ) 2 NiCl 2 or Fe(acac) 2 .

11. The method of claim 2 wherein the compound of formula (VI) is oxidized with SeO 2 , KMnO 4 or CrO 3 .

12. The method of claim 2 wherein the ether comprises THF or diethyl ether.

13. The method of claim 1 wherein R 1 is phenyl, 4-trifluorophenyl, 4-methoxyphenyl or 4-halophenyl or 4-trifluoromethylphenyl.

14. The method of claim 13 wherein R 1 is 4-chlorophenyl.

15. The method of claim 14 wherein R 2 is isopropyl, halo-substituted phenyl or cyclopropyl.

16. The method of claim 15 wherein R 2 is 2-chlorophenyl or 3,5-dichlorophenyl.

17. The method of claim 2 wherein R 1 is 4-trifluoromethylphenyl and R 2 is isopropyl.

18. The method of claim 2 wherein R 1 is 4-chlorophenyl or 4-fluorophenyl and R 2 is 2-chlorophenyl.

19. The method of claim 2 wherein R 1 is 4-methoxyphenyl and R 2 is cyclopropyl.

20. The method of claim 2 wherein R 1 is phenyl and R 2 is 3,4-dichlorophenyl.

Assignees

• Vince Robert
• Vartak Ashish P
• Univ Minnesota

Inventors

• Vince Robert
• Vartak Ashish P

Classifications

• C07D239/26 Primary

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