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

Patent metadata

Field	Value
Publication number	US-9850215-B2
Application number	US-201615173493-A
Country	US
Kind code	B2
Filing date	Jun 3, 2016
Priority date	Dec 31, 2013
Publication date	Dec 26, 2017
Grant date	Dec 26, 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 carbonate 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 carbonate and an alkylating agent,

and
forming a compound of Formula III:

wherein R 1 is selected from the group consisting of:

and

and
R 2 is selected from the group consisting of:

wherein the molar ratio of the compound of Formula II to the alkali carbonate is from 3:1 to 1:1.

2. The method of claim 1 , wherein
a) the contacting step is carried out between 22° C. and 60° C.;
b) the contacting step further includes a solvent selected from the group consisting of: DMF, DMSO, DMA, NMP, and CH 3 CN;
c) the alkali carbonate is selected from the group consisting of: Na 2 CO 3 , K 2 CO 3 , Cs 2 CO 3 , and Li 2 CO 3 ;
d) the alkylating agent is selected from the group consisting of: alkyl halides and benzyl halides; and/or
e) the method further includes the step of diluting a completed reaction mixture with CH 3 CN and 2.5% aqueous Na 2 S 2 O 3 .

3. The method of claim 2 , wherein the alkyl halides and benzyl halides are selected from the group consisting of: methyl iodide, ethyl iodide, and benzyl bromide.

4. The method of claim 2 , wherein the alkali carbonate is Cs 2 CO 3 , and the solvent is DMF.

5. The method of claim 1 , wherein the molar ratio of the compound of Formula II to the alkylating agent is from 1:1 to 3:1.

6. The method of claim 1 , wherein the molar ratio of the compound of Formula II to the alkali carbonate is 2:1 and the molar ratio of the compound of Formula II to the alkylating agent is 1:3.

7. The method of claim 3 , wherein the method further includes the step of diluting a completed reaction mixture with CH 3 CN and 2.5% aqueous Na 2 S 2 O 3 and the ratio of DMF to CH 3 CN is from 1:1 to 3:1 and the ratio of DMF to 2.5% aqueous Na 2 S 2 O 3 is from 1:2 to 2:1.

8. A method of preparing a compound of Formula II, including the steps or:
contacting a compound of Formula I:

with bis-N,O-trimethylsilylacetamide; and
forming a compound of Formula II:

wherein R 1 is selected from the group consisting of:

and
wherein the molar ratio of compound I to bis-N,O-trimethylsilylacetamide is 1:1.1 and the contacting step is carried out at 22° C. to 70° C.

9. The method of claim 8 , wherein
a) the contacting step further includes contacting compound I with CH 3 CN; and/or
b) the method further comprises a step of contacting a bis-N,O-trimethylsilylacetamide treated reaction mixture with an arylsulfonyl chloride.

10. The method of claim 9 , wherein the molar ratio of the compound of Formula I to the arylsulfonyl chloride is from 1:2 to 2:1.

11. The method of claim 2 , wherein
a) the contacting step is carried out between 22° C. and 45° C.;
b) the solvent selected from the group consisting of: DMF, DMA, and NMP;
c) the alkali carbonate is Li 2 CO 3 ; and/or
d) the alkylating agent is an alkyl halide and the alkyl halide is methyl iodide.

12. The method of claim 7 , wherein the ratio of DMF to CH 3 CN is 2:1 and the ratio of DMF to 2.5% aqueous Na 2 S 2 O 3 is 1:1.

13. The method of claim 10 , wherein the molar ratio of the compound of Formula I to the arylsulfonyl chloride is 1:1.1.

Assignees

• Adama Makhteshim 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

• C07D239/47 Primary

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

• A01N43/54

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

• C07D333/10

  Thiophene · CPC title

• C07D409/06

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