4-CHLORO-7-((2-(TRIMETHYLSILYL)ETHOXY)METHYL)-7H-PYRROLO[2,3-D]PYRIMIDINE Chemical Properties

Boiling point:

368.3±37.0 °C(Predicted)

Density 

1.17±0.1 g/cm3(Predicted)

storage temp. 

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

pka

3.00±0.30(Predicted)

Appearance

White to off-white Solid

InChI

InChI=1S/C12H18ClN3OSi/c1-18(2,3)7-6-17-9-16-5-4-10-11(13)14-8-15-12(10)16/h4-5,8H,6-7,9H2,1-3H3

InChIKey

YWBDBLXIRAQZIH-UHFFFAOYSA-N

SMILES

C1=NC(Cl)=C2C=CN(COCC[Si](C)(C)C)C2=N1

Safety Information

Hazard Codes 

Xn

Risk Statements 

22

HazardClass 

IRRITANT

4-CHLORO-7-((2-(TRIMETHYLSILYL)ETHOXY)METHYL)-7H-PYRROLO[2,3-D]PYRIMIDINE Usage And Synthesis

Uses

4-Chloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine is used in the design and preparation of ruxolitinib-vorinostat conjugate derivatives which have dual inhibitory activity against Janus kinase (JAK) and histone deacetylase (HDAC).

Uses

4-Chloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine is used in the design and preparation of ruxolitinib-vorinostat conjugate derivatives which have dual inhibitory activity against Janus kinase (JAK) and histone deacetylase (HDAC).

Synthesis

Sodium hydride (340 mg, 60% dispersed in mineral oil) was added in two portions to a solution of 4-chloropyrrolo[2,3-d]pyrimidine (3a) (1.0 g, 6.5 mmol) in anhydrous DMF (15 mL) under the cooling conditions of an ice-salt bath, keeping the reaction temperature at 0 °C. The reaction temperature was controlled not to exceed 10 °C under nitrogen protection with continuous stirring for 1 hour. Subsequently, 2-(trimethylsilyl)ethoxymethyl chloride (SEMCl) (1.4 g, 8.5 mmol) was slowly added via syringe while ensuring that the temperature did not exceed 10 °C. The reaction mixture was gradually warmed to room temperature and stirring was continued overnight. After completion of the reaction, the reaction was quenched with water, extracted with ethyl acetate (EA) and the organic phase was dried over anhydrous sodium sulfate and concentrated. Purification by preparative fast chromatography (eluent: petroleum ether/ethyl acetate = 19:1) afforded 4-chloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine (3b) (1.834 g, oily product) in 97% yield. Mass spectrum (ESI, m/z): 284 [M + H]+.

References

[1] Patent: EP3360878, 2018, A1. Location in patent: Paragraph 0094; 0095
[2] Patent: CN107226814, 2017, A. Location in patent: Paragraph 0051-0052
[3] Journal of Medicinal Chemistry, 2017, vol. 60, # 20, p. 8336 - 8357
[4] Patent: EP3235819, 2017, A1. Location in patent: Paragraph 0122; 0123
[5] Patent: CN107513067, 2017, A. Location in patent: Paragraph 0082; 0083; 0084; 0085

4-CHLORO-7-((2-(TRIMETHYLSILYL)ETHOXY)METHYL)-7H-PYRROLO[2,3-D]PYRIMIDINE(941685-26-3)Related Product Information

• [4-(1H-Pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]methyl pivalate
• 3-(cyanomethyl)-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]cyclobutylmethyl methanesulfonate
• (4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate
• [4-[1-(1-ethoxyethyl)-1H-pyrazol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-7-yl]methyl
• 4-(1H-Pyrazol-4-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine
• (4-(1-(3-(cyanomethyl)-1-(ethylsulfonyl)azetidin-3-yl)-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate