# US 11,028,057 B2 · Process for the synthesis of 6-chloromethyluracil

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- Number: US 11,028,057 B2
- Document ID: US11028057B2
- Status: Granted
- Kind: B2
- Application number: 16/975,800
- Filed: 2019-02-13
- Published: 2020-12-31
- Granted: 2021-06-08
- Earliest claimed: 2018-02-28
- Assignees: Procos S.P.A.
- Applicants: Procos S.P.A.
- Inventors: Fabio Morana; Stefano Gobbato; Jacopo Roletto; Paolo Paissoni
- Web page: https://patentgrep.com/patent/US11028057B2

## CPC

- C07D 239/46: Two or more oxygen, sulphur or nitrogen atoms
- C07D 239/54: as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
- C07D 239/22: with hetero atoms directly attached to ring carbon atoms
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The invention relates to a process for the synthesis of 6-chloromethyluracil (6-(chloromethyl)pyrimidin-2,4(1H,3H)-dione) from ethyl 4-chloroacetoacetate and S-methylisothiourea hemisulfate via isolation of the novel intermediate 6-(chloromethyl)-6-hydroxy-2-(methylthio)-5,6-dihydropyrimidin-4(1H)-one, and its subsequent treatment with aqueous sulfuric acid. Formula (I).

## Claims

### Claim 1

A process for the preparation of 6-chloromethyluracil comprising the following steps:
a) reacting ethyl 4-chloroacetoacetate and S-methylisothiourea hemisulfate to yield the isolated intermediate 6-(chloromethyl)-6-hydroxy-2-(methylthio)-5,6-dihydropyrimidin-4(1H)-one;
b) reacting said 6-(chloromethyl)-6-hydroxy-2-(methylthio)-5,6-dihydropyrimidin-4(1H)-one with aqueous sulfuric acid to yield 6-chloromethyluracil.

### Claim 2 (depends on 1)

The process according to claim 1, wherein step a) is carried out in the presence of an inorganic base at a temperature ranging between −10° C. and 10° C.

### Claim 3 (depends on 2)

The process according to claim 2, wherein the inorganic base is selected from sodium carbonate, potassium carbonate, sodium bicarbonate and potassium bicarbonate.

### Claim 4 (depends on 3)

The process according to claim 3, wherein the inorganic base is sodium carbonate.

### Claim 5 (depends on 1)

The process according to claim 1, wherein step b) is carried out at a temperature of 40-120° C.

### Claim 6 (depends on 1)

The process according to claim 1, wherein step b) involves in situ conversion of 6-(chloromethyl)-6-hydroxy-2-(methylthio)-5,6-dihydropyrimidin-4(1H)-one to the intermediate 6-chloromethyl-2-(methylthio)pyrimidin-4(1H)-one or its tautomeric form 6-(chloromethyl)-2-(methylthio)pyrimidin-4-ol, which are then converted to 6-chloromethyluracil.

### Claim 7

The compound 6-(chloromethyl)-6-hydroxy-2-(methylthio)-5,6-dihydropyrimidin-4(1H)-one.