4-CHLORO-5-METHOXY-2-(METHYLSULFANYL)PYRIMIDINE Chemical Properties

Melting point:

73-77°

Boiling point:

285.5±20.0 °C(Predicted)

Density 

1.36±0.1 g/cm3(Predicted)

storage temp. 

under inert gas (nitrogen or Argon) at 2-8°C

pka

-0.39±0.29(Predicted)

Appearance

Light yellow to brown Solid

Safety Information

Risk Statements 

36/37/38

Safety Statements 

26-36

HazardClass 

IRRITANT

HS Code 

29335990

4-CHLORO-5-METHOXY-2-(METHYLSULFANYL)PYRIMIDINE Usage And Synthesis

Chemical Properties

White solid

Synthesis

The general procedure for the synthesis of 4-chloro-5-methoxy-2-(methylthio)pyrimidine from 5-methoxy-4-hydroxy-2-methylthiopyrimidine was as follows: 1. To a round-bottomed flask containing ethyl formate (6 mL, 0.062 mol) and ether (30 mL) in an ice-water bath was added Na (1.4 g, 0.062 mol), followed by dropwise addition of methyl 2-methoxyacetate (6.5 g, 0.062 mol). The reaction mixture was stirred for 4 hours at room temperature. 2. Upon completion of the reaction, the reaction was quenched by the addition of ice water (25 mL) and the aqueous phase was separated. 3. To the aqueous phase, S-methylisothiourea (5.6 g, 0.062 mol) and KOH (2.2 g, 0.062 mol) were added sequentially and the reaction was heated to 65 °C for 1 hour. 4. After cooling, the reaction mixture was neutralized with 37% HCl, the crude product was collected by vacuum filtration and recrystallized from 95% ethanol to give Intermediate 2 as white needle-like crystals (4.3 g, 40.1% yield). 5. Intermediate 2 (1.7 g, 0.01 mol) was slowly added to POCl3 (4.6 g, 0.03 mol) in an ice-water bath, and the reaction was heated to 80 °C for 1 hour. 6. After the reaction was completed, it was cooled to room temperature, neutralized with 25% ammonia, filtered the precipitated solid, recrystallized with petroleum ether and decolorized with activated carbon to obtain Intermediate 3 as a light yellow solid (1.8 g, 95.2% yield). 7. Intermediate 3 was dissolved in methanol (10 mL), 50% hydrazine hydrate solution (1.6 g, 0.015 mol) was added dropwise under an ice-water bath, and the reaction was heated to 50 °C. The reaction progress was monitored by TLC. 8. Upon completion of the reaction, the reaction was cooled, the solvent was removed under reduced pressure, and the solid was recrystallized from ethyl acetate and petroleum ether to afford 5-methoxy-2-(methylthio)pyrimidin-4-ylhydrazine (4,1.1 g, 96.2% yield).

References

[1] Letters in Drug Design and Discovery, 2016, vol. 13, # 4, p. 329 - 334
[2] Patent: WO2004/50640, 2004, A1. Location in patent: Page 22
[3] Patent: WO2007/88999, 2007, A1. Location in patent: Page/Page column 167

4-CHLORO-5-METHOXY-2-(METHYLSULFANYL)PYRIMIDINE(87026-45-7)Related Product Information

• Propylthiouracil
• 4-Chloropyrimidine
• 4-Chloro-2-methylthiopyrimidine
• 4-CHLORO-2-[(2,6-DICHLOROBENZYL)SULFANYL]-5-METHOXYPYRIMIDINE
• ETHYL 2-[(4-CHLORO-5-METHOXY-2-PYRIMIDINYL)SULFANYL]ACETATE
• 4-CHLORO-2-[(2,4-DICHLOROBENZYL)SULFANYL]-5-METHOXYPYRIMIDINE
• 4-CHLORO-5-METHOXY-2-(METHYLSULFANYL)PYRIMIDINE
• 4-CHLORO-2-[(4-CHLOROBENZYL)SULFANYL]-5-METHOXYPYRIMIDINE
• 4-CHLORO-2-[(3,4-DICHLOROBENZYL)SULFANYL]-5-METHOXYPYRIMIDINE