4,6-dichloropyrimidine-5-carbonitrile

4,6-dichloropyrimidine-5-carbonitrile - Names and Identifiers

Name	4,6-Dichloropyrimidine-5-carbonitrile
Synonyms	4,6-Dichloro-5-cyanopyriM... 4,6-Dichloro-5-cyanopyrimidine 4,6-Dichloropyrimidine-5-carbonitrile 4,6-Dichloro-5-pyrimidinecarbonitrile 4,6-dichloropyrimidine-5-carbonitrile 5-PyriMidinecarbonitrile, 4,6-dichloro- 5-Pyrimidinecarbonitrile, 4,6-dichloro- 4-aMino-2,6-dichloropyriMidine-5-carbonitrile 4,6-Dichloropyrimidine-5-carbonitrile 4,6-Dichloro-5-cyanopyrimidine
CAS	5305-45-3
EINECS	200-110-4
InChI	InChI=1/C5HCl2N3/c6-4-3(1-8)5(7)10-2-9-4/h2H

4,6-dichloropyrimidine-5-carbonitrile - Physico-chemical Properties

Molecular Formula	C5HCl2N3
Molar Mass	173.99
Density	1.60
Melting Point	145 °C
Boling Point	335.2±37.0 °C(Predicted)
Flash Point	156.5°C
Vapor Presure	0.000122mmHg at 25°C
pKa	-7.00±0.26(Predicted)
Storage Condition	under inert gas (nitrogen or Argon) at 2-8°C
Refractive Index	1.59

4,6-dichloropyrimidine-5-carbonitrile - Reference Information

Application

4, 6-dichloropyrimidin-5-methenitrile and its derivatives are an important class of pharmaceutical intermediates, which can be used to prepare drugs, such as RUP3 receptor antagonists and PI3K kinase inhibitors.

preparation

synthesis of N-((4, 6-dihydroxy-pyrimidine -5-yl) methylene)-N-methylammonium chloride salt DCM(600ml) and POCl3(80ml,862mmol) are sequentially added to the reaction bottle, stirred evenly, and protected by nitrogen, cooling to 5-10 ℃, dropping DMF(66.04ml,856mmol) solution dissolved in DCM(200ml), dropping and stirring for 15-20min, heating to 25-30 ℃, stirring for 1-2 hours, adding 4, 6-dihydroxypyrimidine (80g,714mmol) to the reaction solution, reacting at 25-30 ℃ for 22 hours, filtering, washing the filter cake twice with DCM(150ml), and draining, vacuum drying at 40-45 ℃ to obtain 139.4g yellow solid, which is the target compound. 1H

NMR(400MHz,DMSO)δ9.03(s,1H),8.47-8.40(m,1H),3.62(d,J=0.8Hz,3H),3.30(d,J=0.9Hz,3H). LC-MS:[M]: Synthesis of 1684, 6-dihydroxypyrimidine -5-formaldehyde oxime Add hydroxylamine hydrochloride (122.85g,1.768mol), water (240ml) and ethanol (1200ml) to the reaction bottle. After the solution is clarified, add N-((4, 6-dihydroxypyrimidine -5-yl) methylene)-N-methylammonium chloride (120g,0.589mol) in batches, then react at 20-30°C for 17 hours. Filtration, the resulting filter cake was washed twice with ethanol (240ml), and then vacuum dried at 40-45 ℃ to obtain 89.4g of product, which is the target compound. 1H
NMR(400MHz,DMSO)δ11.45(s,1H),8.83(s,1H),8.32(s,1H). LC-MS:[M H]: Synthesis of 1564,6-dihydroxypyrimidine -5-methanonitrile Add POCl3(5ml,53.65mmol), 4,6-dihydroxypyrimidine -5-formaldehyde oxime (1.0g,8.92mmol) to the reaction bottle in sequence, stir, raise the temperature to 80-90 ℃ for reaction for 2 hours, add toluene and acetonitrile in sequence after cooling, and evaporate to nearly dry, add methanol (4ml) to the reaction bottle, stir, filter, wash the filter cake with a small amount of methanol, drain, and obtain 0.323g yellow solid, which is the target compound. Synthesis of 4,6-dichloropyrimidine -5-methonitrile Add acetonitrile (850ml) and POCl3(254.60ml,2.732mol) to the reaction bottle, add DIPEA(377.68ml,2.278mol) dropwise at 20-30 ℃, after the dropwise addition is completed, add 4,6-dihydroxypyrimidine -5-formaldehyde oxime (85g,0.548mol) in batches, after heating to 80-85 ℃ for 3 hours, the solution is concentrated under reduced pressure, and the concentrated solution is dropped into water (1.7L) for quenching, and the product is precipitated from the water. The filtered filter cake was washed twice with water (170ml), the wet product was dissolved in EA(1080ml), decolorized with activated carbon at 45-50 ℃, the filtered filter was concentrated and dried, pulped with a mixed solvent of EA and DCM, and the filtered filter cake was dried under reduced pressure at 45-50 ℃ to obtain 45.3g of solid as the target compound.

Last Update：2024-04-09 01:59:58