5-fluoro-4-imino-3-(alkyl/substituted alkyl)-1-(arylsulfonyl)-3,4-dihydropyrimidin-2(1H)-one and processes for their preparation

Patent metadata

Field	Value
Publication number	US-9840476-B2
Application number	US-201615173529-A
Country	US
Kind code	B2
Filing date	Jun 3, 2016
Priority date	Dec 31, 2013
Publication date	Dec 12, 2017
Grant date	Dec 12, 2017

Abstract

Provided herein are 5-fluoro-4-imino-3-(alkyl/substituted alkyl)-1-(arylsulfonyl)3,4-dihydropyrimidin-2(1H)-one and processes for their preparation which may include the use of an alkali alkoxide and an alkylating agent

First claim

What is claimed is:

1. A method of making compounds of Formula III, including the steps of:
contacting a compound of Formula II with an alkali alkoxide and an alkylating agent,

and
forming a compound of Formula III:

wherein R 1 is selected from the group consisting of:

and
R 2 is selected from the group consisting of:

2. The method of claim 1 , wherein the contacting step is carried out between 22° C. and 60° C.

3. The method of claim 1 , wherein the contacting step further includes a solvent selected from the group consisting of: DMF, DMSO, DMA, NMP, and CH 3 CN.

4. The method of claim 1 , wherein the alkali alkoxide is selected from the group consisting of: KO t Bu, CH 3 ONa, CH 3 CH 2 ONa, CH 3 CH 2 OLi, CH 3 OLi, CH 3 CH 2 OK, and CH 3 CH 2 ONa.

5. The method of claim 1 , wherein the alkylating agent is selected from the group consisting of: alkyl halides and benzyl halides.

6. The method of claim 5 , wherein the alkylating agent is an alkyl halide.

7. The method of any one of claims 3 , 4 , 5 , or 6 , wherein the alkali alkoxide is KO t Bu, and the solvent is DMF.

8. The method of claim 7 , wherein the molar ratio of the compound of Formula II to the alkali alkoxide is from about 3:1 to about 1:1 and the molar ratio of the compound of Formula II to the alkylating agent is from about 1:1 to about 3:1.

9. The method of claim 8 , wherein a molar ratio of the compound of Formula II to alkali alkoxide is about 2:1 and a molar ratio of the compound of Formula II to alkylating agent is about 1:3.

10. The method of claim 9 , further including the step of diluting a completed reaction mixture with CH 3 CN and 2.5% aqueous Na 2 S 2 O 3 .

11. The method of claim 10 , wherein the ratio of DMF to CH 3 CN is from about 1:1 to about 3:1 and the ratio of DMF to 2.5% aqueous Na 2 S 2 O 3 is from about 1:2 to about 2:1.

12. The method of claim 11 , wherein the ratio of DMF to CH 3 CN is about 2:1 and the ratio of DMF to 2.5% aqueous Na 2 S 2 O 3 is about 1:1.

13. The method of claim 2 , wherein the contacting step is carried out between 22° C. and 45° C.

14. The method of claim 3 , wherein the solvent selected from the group consisting of: DMF, DMA, and NMP.

15. The method of claim 6 , wherein the alkyl halide is methyl iodide.

16. The method of claim 6 , wherein the alkyl halide is ethyl iodide.

17. The method of claim 5 , wherein the alkylating agent is a benzyl halide.

18. The method of claim 17 , wherein the benzyl halide is benzyl bromide.

19. The method of claim 1 , wherein R is

and R 2 is

20. The method of claim 3 , wherein the solvent is DMF.

Assignees

• Adama Makhteshim Ltd
• Adama Makteshim Ltd

Inventors

• Choy Nakyen
• Ross Jr Ronald

Classifications

• C07D239/24 Primary

  having three or more double bonds between ring members or between ring members and non-ring members · CPC title

• A01N43/54

  1,3-Diazines; Hydrogenated 1,3-diazines · CPC title

• C07D239/47 Primary

  One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine · CPC title

• C07D409/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C07D333/10

  Thiophene · CPC title