2,4-Dichloro-6-methyl-5-pyrimidinecarboxylic acid methyl ester Chemical Properties

Boiling point:

292℃

Density 

1.435

Flash point:

131℃

storage temp. 

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

pka

-3.83±0.39(Predicted)

Appearance

White to yellow Solid

2,4-Dichloro-6-methyl-5-pyrimidinecarboxylic acid methyl ester Usage And Synthesis

Uses

2,4-Dichloro-6-methyl-5-pyrimidinecarboxylic Acid Methyl Ester is used in preparation of 4,6,7-Trisubstituted 1,2-dihydropyrrol[3,4-c]pyridin/pyrimidin-3 -one derivatives useful as Btk kinase inhibitors.

Synthesis

General procedure for the synthesis of methyl 2,4-dichloro-6-methylpyrimidine-5-carboxylate from methyl 2,4-dihydroxy-6-methylpyridine-5-carboxylate: 6-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid methyl ester (1 g, 5.43 mmol) was suspended in POCl3 (10 mL) and N,N-dimethylaniline (10 drops ). The reaction mixture was heated at 105 °C for 6 h until a clarified solution was formed. Upon completion of the reaction, the mixture was cooled to room temperature, concentrated under reduced pressure and subsequently poured into ice water and extracted with ethyl acetate (EtOAc). The organic phases were combined, washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give methyl 2,4-dichloro-6-methylpyrimidine-5-carboxylate (940 mg, 78% yield) as a yellow-green solid. Mass spectrometry analysis: [M + H]+ C7H6Cl2N2O2 calculated value was 222, measured values were 221 and 223.

References

[1] Patent: US2011/152273, 2011, A1. Location in patent: Page/Page column 28
[2] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 24, p. 5947 - 5950
[3] Patent: WO2015/131080, 2015, A1. Location in patent: Paragraph 00270; 00274
[4] Patent: US2014/148454, 2014, A1. Location in patent: Paragraph 0676
[5] Patent: WO2014/82739, 2014, A1. Location in patent: Page/Page column 59

2,4-Dichloro-6-methyl-5-pyrimidinecarboxylic acid methyl ester(36745-93-4)Related Product Information

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