Pyrimidine, 5-bromo-2-(trifluoromethyl)-

5-bromo-2-(trifluoromethyl)pyrimidine:; A mixture of 1.77 g (30.35 mmoles, 1.33 eq.) of KF and 5.79 g (30.35 mmoles, 1.33 eq.) of CuI were stirred and heated together using a heat gun under vacuum (1 mm) for 20 min. After cooling, 20 ml_ of DMF and 20 ml of NMP were added followed by 4.1 ml_ (27.38 mmoles, 1.20 eq.) of CFA mixture of 5-bromo-2-iodo-pyrimidine (30 g, 0.11 mol), TMSCFA mixture of 5-bromo-2-iodopyrimidine (10 g, 35.10 mmol, 1.00 equiv), trimethyl(trifluoromethyl)silane (20 g, 140.65 mmol, 4.00 equiv), KF (4.1 g, 70.57 mmol, 2.00 equiv), and CuT (13 g, 68.26 mmol, 2.00 equiv) in NMP (80 mL) was stirred overnight at 70°C under nitrogen. The reaction was quenched by 200 mL of ammonia hydroxide, extracted with ethyl acetate, dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue was purified by a silica gel column eluting with petroleum ether to afford the title compound 1.1 g (14percent) of 5-bromo-2- (trifluoromethyl)pyrimidine as a light yellow solid.Under nitrogen protection, The reaction flask was charged with 2-amino-5-bromopyrimidine (1.0 mol)And 20percent hydrochloric acid (1.5 mol), After stirring until completely clear, The temperature was controlled at -5 ~ 5 slowly dropwise sodium nitrite (1.2mol) aqueous solution, after the addition was completed, Incubated for 2 hours with stirring, Confirm the reaction is complete.Trifluoromethylboronic acid (2.0 mol) and potassium acetate (2.0 mol) were dissolved in water, Slowly began to drop into the reaction solution, Dropping process, Clear gas escapes, By dropping the speed to control the reaction temperature does not exceed 20 , Dropping is completed, Incubated for 2 hours with stirring, The reaction is completed, Add ethyl acetate extraction, Saturated brine washing, After vacuum distillation, After adding cold water beating, Filtered to afford 2-trifluoromethyl-5-bromopyrimidine as an off-white solid, Yield 67percent.24 g of 2-trifluoromethylpyrimidine was added to 200 ml of acetic acid, 50 g of bromine was added dropwise, and the mixture was heated under reflux overnight, cooled, water and ethyl acetate were added, and the mixture was separated, and the organic phase was collected, dried and concentrated to give 29 g. 5-Bromo-2-trifluoromethylpyrimidine.Add 24g of 2-trifluoromethylpyrimidine to 200ml of acetic acid, 50 g of bromine was added dropwise, and the mixture was stirred under heating and refluxed overnight.Cool, add water and ethyl acetate, extract the liquid, Collect the organic phase, dry, concentrate, 29 g of 5-bromo-2-trifluoromethylpyrimidine were obtained.

5-Bromo-2-trifluoromethylpyrimidine was used in the preparation of pyrimidinone compounds as Lp-PLA2 inhibitors.

Molecular Weight:226.98
XLogP3:1.8
Hydrogen Bond Acceptor Count:5
Exact Mass:225.93535
Monoisotopic Mass:225.93535
Topological Polar Surface Area:25.8
Heavy Atom Count:11
Complexity:130
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes