| Identification | Back Directory | [Name]
5-(4-Bromophenyl)-4,6-dichloropyrimidine | [CAS]
146533-41-7 | [Synonyms]
macitentan INT
5-(4-broMophenyl)-4
MacitentanImpurity44
Macitentan Impurity 26
Macitentan Intermediate 1
Macitentan Impurity 26 CRS
potassiuM (N-propylsulfaMoyl)aMide
(4-broMophenyl)-4,6-dichloroPyriMidine
4,6-Dichloro-5-(4-bromophenyl)pyrimidine
5-(4-broMophenyl)-4,6-dichloropyriMidine
5-(4-Bromophenyl)-4,6-dichloro-Pyrimidin
5-(4-Bromophenyl)-4,6-dichloro-1,3-diazine
PyriMidine, 5-(4-broMophenyl)-4,6-dichloro-
5-(4-Bromophenyl)-4,6-dichloropyrimidine(BPDCP)
5-(4-Bromophenyl)-4,6-dichloropyrimidine(146533-41-7)
5-(4-Bromo-phenyl)-4,6-dichloro-pyrimidine (Int. for MACITENTAN)
5-(4-bromophenyl)-4,6-dichloropyrimidineQ: What is
5-(4-bromophenyl)-4,6-dichloropyrimidine Q: What is the CAS Number of
5-(4-bromophenyl)-4,6-dichloropyrimidine Q: What is the storage condition of
5-(4-bromophenyl)-4,6-dichloropyrimidine Q: What are the applications of
5-(4-bromophenyl)-4,6-dichloropyrimidine | [Molecular Formula]
C10H5BrCl2N2 | [MDL Number]
MFCD13151897 | [MOL File]
146533-41-7.mol | [Molecular Weight]
303.97 |
| Chemical Properties | Back Directory | [Melting point ]
98.0 to 102.0 °C | [Boiling point ]
368.7±42.0 °C(Predicted) | [density ]
1.677±0.06 g/cm3(Predicted) | [storage temp. ]
Inert atmosphere,2-8°C | [solubility ]
Chloroform (Slightly), DMSO (Slightly) | [form ]
Solid | [pka]
-4.92±0.26(Predicted) | [color ]
Off-White | [Sensitive ]
Light Sensitive | [InChI]
InChI=1S/C10H5BrCl2N2/c11-7-3-1-6(2-4-7)8-9(12)14-5-15-10(8)13/h1-5H | [InChIKey]
WEEFLZORZXLIJE-UHFFFAOYSA-N | [SMILES]
C1=NC(Cl)=C(C2=CC=C(Br)C=C2)C(Cl)=N1 |
| Questions And Answer | Back Directory | [Uses]
5-(4-Bromophenyl)-4,6-dichloropyrimidine is a reactant used in the synthesis of Macitentan, an orally active dual endothelin receptor antagonist. |
| Hazard Information | Back Directory | [Description]
5 - (4-Bromophenyl)-4, 6- dichloropyrimidine is a key intermediate and has a wide range of
applications in the pharmaceutical and chemical fields. | [Synthesis Reference(s)]
[1] Hou, S., Chen, C., Wang, P., Sun, C.-F., Zheng, P., & Xu, S. (2016). Synthesis of 5-(4-bromophenyl) - 4, 6- dichloropyrimidine. 0. https://doi.org/10.2991/ICMMCT-16.2016.151 | [Synthesis]
Dimethyl 2-(4-bromophenyl) malonate (6)
A solution of methyl 2-(4-bromophenyl)acetate (5) (206.8 g, 0.9 mol) in THF (400mL), then it
was added drop-wise to a suspension of sodium hydride (65.0 g,2.71 mol) in THF solution(1000mL)
at room temperature, control the drip rate and the temperature was kept 25 ~ 27 , when dropping ℃
was completed, keep the temperature for 1h, then dimethyl carbonate (DMC) (325.1 g, 3.6 mol) was
added, keep the reaction for 14 h. After cooling to -10 , the s ℃ olution is adjusted to pH 6~7 using
hydrochloric acid (36%) then removed THF under reduced pressure, ethyl acetate (1600mL) was
added to the solution, the organic phase was washed with hydrochloric acid solution (1 mol/L, 36%)
saturated brine and was dried by magnesium sulfate, then it was distilled under reduced pressure to
afford yellow oil. The yellow oil was solidified by cyclohexane, after mixture was filtered and
driedto obtain yellow solid, then re-crystallized with ethanol- acetone (5:2) to obtain 6 as white
solid (192.9 g).yield: 72.3%. M.p.77-79 , ℃ MS; 308.8 [M + Na] +
, 596.7[2M+Na]+
.
5-(4-Bromophenyl) pyrimidine-4, 6-diol (7)
Sodium (46.9g, 2.0mol) was slowly added into methanol (600mL) at 0 . Dimethyl ℃ – 2 - ( 4
–bromophenyl ) malonate(192.9g,0.67mol) was dissolved in methanol (380mL) added into the
solution of sodium methoxide, after dropping, keep the reaction for 1h at roo was added, heated to
40 for 3.5 h. After cooling to room temperature, methanol was ℃ distilled off under reduced
pressure, the solution of citric acid was added into the residue and stirred for 1 hours. The
precipitated solid was suction filtered, and the solid w m temperature, then formamidineas washed
with water, then dried to give a yellow solid. The crude product was added into cyclohexane
(900mL) was stirred for 3h at room temperature, then the precipitated solid was suction filtered, the
solid was washed with cyclohexane and dried to obtain7 as light yellow solid (149.1 g ,84.4%).
M.p.178-180 ℃; MS; 269.0[M+H] +
, 288.9[M + Na] +
.
5-(4-Bromophenyl)-4, 6-dichloropyrimidine (1)
5-(4-Bromophenyl) pyrimidine-4, 6-diol (53.4g, 0.2mol) was slowly added into POCl3 (427mL),
refluxed for 8h. POCl3 was distilled off under reduced pressure, then the black viscous residue was
poured into ice water (1000mL), The solution was adjusted to pH9~10 using potassium carbonate.
The product was filtered off, washed with water and dried under reduced pressure to afford
5-(4-bromophenyl)-4, 6-dichloropyrimidine (1) as white solid (52.6 g, 86.5%). M. P. 101 -102 , ℃
MS: 302 [M+H] +
; 1 H -NMR (300 MHz, DMSO-d 6 ) δ 8.96(s, 1H,Ar-H), 7.72(d, J = 8.5 Hz, 2H,
Ar-H), 7.39(d, J = 8.5Hz, 2H, Ar-H). | [References]
[1] Journal of Medicinal Chemistry, 2012, vol. 55, # 17, p. 7849 - 7861
[2] Monatshefte fur Chemie, 2018, vol. 149, # 3, p. 653 - 661
[3] Bioorganic and Medicinal Chemistry, 2007, vol. 15, # 4, p. 1586 - 1605
[4] Patent: WO2004/50640, 2004, A1. Location in patent: Page 31
[5] Patent: WO2009/24906, 2009, A1. Location in patent: Page/Page column 13-14 |
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