| Identification | More | [Name]
5-Bromo-2-chloropyrimidine | [CAS]
32779-36-5 | [Synonyms]
2C5BP
2-CHLORO-5-BROMOPYRIMIDINE
5-BROMO-2-CHLOROPYRIMIDINE
5-BROMO-2-CHLOROPYRIMIDNE
PYRIMIDINE, 5-BROMO-2-CHLORO-
5-BROMO-2-CHLOROPYRIMIDINE(MINIMUM85%)
MAJORIMPURITYIS2,5-DIBROMOPYRIMIDINE
5-BROMO-2-CHLOROPYRIMIDINE(MINIMUM95%)
5-Bromo-2-chloropyrimidine 85%
5-Bromo-2-chloropyrimidine, 98+% | [EINECS(EC#)]
629-214-8 | [Molecular Formula]
C4H2BrClN2 | [MDL Number]
MFCD00483232 | [Molecular Weight]
193.43 | [MOL File]
32779-36-5.mol |
| Chemical Properties | Back Directory | [Appearance]
Off-white to beige crystalline powder | [Melting point ]
73-79 °C (lit.) | [Boiling point ]
95°C 15mm | [density ]
1.859±0.06 g/cm3(Predicted) | [Fp ]
95°C/15mm | [storage temp. ]
Keep in dark place,Sealed in dry,Room Temperature | [solubility ]
soluble in Methanol | [form ]
Crystalline Powder | [pka]
-2.84±0.22(Predicted) | [color ]
Off-white to beige | [Water Solubility ]
insoluble | [Detection Methods]
HPLC,NMR | [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 Data | Back Directory | [Hazard Codes ]
Xi | [Risk Statements ]
R36/37/38:Irritating to eyes, respiratory system and skin . | [Safety Statements ]
S26:In case of contact with eyes, rinse immediately with plenty of water and seek medical advice .
S36/39:Wear suitable protective clothing and eye/face protection .
S37/39:Wear suitable gloves and eye/face protection .
S36:Wear suitable protective clothing . | [RIDADR ]
UN 3335 | [WGK Germany ]
3
| [Hazard Note ]
Irritant | [HazardClass ]
IRRITANT | [HS Code ]
29335900 |
| Hazard Information | Back Directory | [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 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].
| [Synthesis]
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.
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