4-CHLORO-2-(TRIFLUOROMETHYL)PYRIMIDINE Chemical Properties

Boiling point:

115.4±40.0 °C(Predicted)

Density 

1.504g/ml

storage temp. 

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

solubility 

Chloroform (Slightly), Methanol (Slightly)

pka

-3.28±0.20(Predicted)

form 

Oil

color 

Clear Colourless

InChI

InChI=1S/C5H2ClF3N2/c6-3-1-2-10-4(11-3)5(7,8)9/h1-2H

InChIKey

OVEGSCLVOXWLIV-UHFFFAOYSA-N

SMILES

C1(C(F)(F)F)=NC=CC(Cl)=N1

Safety Information

HazardClass 

IRRITANT

HS Code 

2933998090

4-CHLORO-2-(TRIFLUOROMETHYL)PYRIMIDINE Usage And Synthesis

Uses

4-Chloro-2-(trifluoromethyl)pyrimidine is used to prepare trifluoromethyl(pyrimidin-??2-??yl)??azetidine-??2-??carboxamides as potent, orally bioavailable TGR5 (GPBAR1) agonists.

Synthesis

General procedure for the synthesis of 4-chloro-2-(trifluoromethyl)pyrimidines from 2-(trifluoromethyl)pyrimidin-4-ol: Intermediate 39a: potassium 2-[4-(trifluoromethyl)pyrimidin-2-yl]acetate [00458] 2-(Trifluoromethyl)-4-pyrimidinol (4.00 g, 24.38 mmol) was dissolved in phosphorochloridic acid (20 mL, 214.57 mmol) and a drop of N,N-dimethylformamide was added as a catalyst. The reaction mixture was heated to 120 °C and kept at this temperature for 2 hours. Upon completion of the reaction, the mixture was cooled to room temperature and subsequently concentrated under vacuum to remove the excess phosphoryl chloride. The residue was diluted with ethyl acetate (100 mL) and washed sequentially with water (100 mL) and saturated brine (100 mL). The organic layer was dried with anhydrous sodium sulfate, filtered and concentrated in vacuum. The residue was purified by column chromatography using a heptane solution of 50% ethyl acetate as eluent to give 4-chloro-2-(trifluoromethyl)pyrimidine (2.52 g, 13.8 mmol, 56% yield) as a light brown liquid. 1H NMR (DMSO-d6, 400MHz) δ/ppm: 9.07 (1H, d, J = 5.6Hz), 8.11 (1H, d, J = 5.6Hz). MS Method 3: RT: 3.61 min, m/z 182.0 [M + H]+.

References

[1] Patent: CN106883185, 2017, A. Location in patent: Paragraph 0022
[2] Patent: WO2006/99231, 2006, A1. Location in patent: Page/Page column 89
[3] Patent: WO2016/51193, 2016, A1. Location in patent: Paragraph 00456; 00457; 00458
[4] Patent: WO2006/136442, 2006, A1. Location in patent: Page/Page column 29-30
[5] Patent: WO2006/72831, 2006, A1. Location in patent: Page/Page column 55-56

4-CHLORO-2-(TRIFLUOROMETHYL)PYRIMIDINE(1514-96-1)Related Product Information

• 4-CHLORO-2-(TRIFLUOROMETHYL)QUINAZOLINE
• 4-CHLORO-5,6-DIMETHYL-2-(TRIFLUOROMETHYL)PYRIMIDINE
• Ethyl 4-chloro-2-(trifluoromethyl)pyrimidine-5-carboxylate
• 4-CHLORO-2-(TRIFLUOROMETHYL)PYRIMIDINE
• 2-CHLORO-4-(TRIFLUOROMETHYL)PYRIMIDINE-5-CARBONYL CHLORIDE
• Acetamide, 2,2-dichloro-N-[p-cinnamoyl-β-hydroxy-α-(hydroxymethyl)phenethyl]-,D-threo-(8CI)
• ETHYL 2-CHLORO-4-(TRIFLUOROMETHYL)PYRIMIDINE-5-CARBOXYLATE,Ethyl 2-chloro-4-(trifluoromethyl)pyrimidine-
• 2-Chloro-4-(trifluoromethyl)pyrimidine 99%,2-Chloro-4-(trifluoromethyl)pyrimidine99%,2-CHLORO-4-(TRIFLUOROMETHYL)PYRIMIDINE
• 4-CHLOROBENZYL 2-CHLORO-4-(TRIFLUOROMETHYL)PYRIMIDINE-5-CARBOXYLATE
• 6-Chloro-4-(trifluoromethyl)pyrimidine
• 2-AMINO-4-CHLORO-6-TRIFLUOROMETHYL-PYRIMIDINE
• BENZYL 2-CHLORO-4-(TRIFLUOROMETHYL)PYRIMIDINE-5-CARBOXYLATE
• METHYL 2-CHLORO-4-(TRIFLUOROMETHYL)PYRIMIDINE-5-CARBOXYLATE,Methyl2-chloro-4-(trifluoromethyl)pyrimidine-5
• 2-Trifluoromethylpyrimidine
• 4,8-DICHLORO-2-TRIFLUOROMETHYL-QUINAZOLINE
• 4,6-dichloro-2-(trifluoromethyl)pyrimidine
• 4,6-DICHLORO-5-NITRO-2-(TRIFLUOROMETHYL)PYRIMIDINE
• QUINAZOLINE, 6-BROMO-4-CHLORO-2-(TRIFLUOROMETHYL)-