ChemicalBook Product Catalog Pharmaceutical intermediates Heterocyclic compound Pyrimidines Chloropyrimidine 5-Bromo-2-chloropyrimidine

5-Bromo-2-chloropyrimidine

Product Name5-Bromo-2-chloropyrimidine
CAS32779-36-5
MFC4H2BrClN2
MW193.43
EINECS629-214-8
MOL File32779-36-5.mol

Chemical Properties

Melting point	73-79 °C (lit.)
Boiling point	95°C 15mm
Density	1.859±0.06 g/cm3(Predicted)
Flash point	95°C/15mm
storage temp.	Keep in dark place,Sealed in dry,Room Temperature
solubility	soluble in Methanol
pka	-2.84±0.22(Predicted)
form	Crystalline Powder
color	Off-white to beige
Water Solubility	insoluble
BRN	507955
Stability	Hygroscopic
InChI	InChI=1S/C4H2BrClN2/c5-3-1-7-4(6)8-2-3/h1-2H
InChIKey	XPGIBDJXEVAVTO-UHFFFAOYSA-N
SMILES	C1(Cl)=NC=C(Br)C=N1
CAS DataBase Reference	32779-36-5(CAS DataBase Reference)

Safety Information

Hazard Codes	Xi
Risk Statements	36/37/38
Safety Statements	26-36/39-37/39-36
RIDADR	UN 3335
WGK Germany	3
HazardClass	IRRITANT
HS Code	29335990
Storage Class	11 - Combustible Solids
Hazard Classifications	Eye Irrit. 2 Skin Irrit. 2 STOT SE 3

MSDS

Provider	Language
ACROS	English
SigmaAldrich	English
ALFA	English

Usage And Synthesis

Description

5-Bromo-2-chloropyrimidine is a halogenated pyrimidine analogue containing chloro and bromo substituents at positions 2 and 5 of the benzene ring structure. The compound is used as a pharmaceutical intermediate in the preparation of macitentan, an endothelin receptor antagonist drug for the treatment of pulmonary hypertension.

Chemical Properties

Off-white to beige crystalline powder

Uses

5-Bromo-2-chloropyrimidine is applied as a pharmaceutical intermediate, in the synthesis of pharmaceutical goods such as inhibitors. It is also employed in the cross-coupling reactions of indium organometallics with 2,5-dihalopyrimidines.

Uses

5-Bromo-2-chloropyrimidine is a intermediate in the synthesis of pharmaceutical goods such as inhibitors.

Preparation

Under nitrogen protection, 35 g (0.2 mol) of 2-hydroxy-5-bromopyrimidine, 61.3 g (0.4 mol) of phosphorus oxychloride, and 200 mL of toluene were added into the reaction flask. At 35 ℃, triethylamine 40.5g was added and then heated up at 80-85 ℃. Stir the reaction for 6 hours, sampling HPLC to detect the raw material (less than 2%), and lower the temperature. After concentrating the mixture under reduced pressure to remove most of the toluene and Phosphorus oxychloride, put the reaction solution into 10°C water, and adjust pH=8-9 with 20% sodium carbonate aqueous solution. Finally, 5-Bromo-2-chloropyrimidine was obtained after purification.

Reactivity Profile

5-Bromo-2-chloropyrimidine, a 2,5-dihalopyrimidine, is a useful organic electrophiles. It could react with tri(3-indolyl)indium reagent through cross-coupling reaction. Other aryl- and heteroarylindium reagents, such as thiophenyl-, pyridyl-, naphthyl-, and alkynylindium reagents, also reacted with 5-bromo-2- chloropyrimidine to afford the corresponding 2-chloro-5-substituted pyrimidines[1].
5-Bromo-2-chloropyrimidine

Synthesis

38353-06-9

32779-36-5

General procedure for the synthesis of 5-bromo-2-chloropyrimidine from 5-bromopyrimidin-2(1H)-one: Phosphoryl chloride (225 mL, 2.4 mol, 1.4 eq.) was slowly added to a reaction flask containing a mixture of 5-bromo-2-hydroxypyrimidine (30 g, 0.17 mol) and dimethylaniline (7.5 mL). The reaction mixture was heated to reflux under nitrogen protection for 4 hours. Upon completion of the reaction, the dark brown reaction mixture was cooled to room temperature and then carefully poured into ice water. The mixture was extracted with ether to separate the organic phase. The organic phase was subsequently washed with sodium bicarbonate solution to remove acidic impurities. The washed organic phase was dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford the target product 5-bromo-2-chloropyrimidine (25 g, 75% yield). [Ref: Goodby, J.W.; Hird, M.; Lewis, R.A.; Toyne, K.J. J. Chem. Soc., Chem. Commun. 1996, 2719.]

References

[1] Mosquera A, et al. Cross-Coupling Reactions of Indium Organometallics with 2,5-Dihalopyrimidines: Synthesis of Hyrtinadine A. Organic Letters, 2008; 10: 3745–3748.

5-Bromo-2-chloropyrimidine

Chemical Properties

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Usage And Synthesis

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