22536-67-0

Basic information

• Product Name: 2,5-Dichloropyrimidine
• Synonyms: 2,5-DICHLOROPYRIMIDINE;Pyrimidine, 2,5-dichloro- (7CI,8CI,9CI);2,5-DICHLOROPYRIMIDINE,PURITY:95% MIN(HPLC);Pyrimidine, 2,5-dichloro-;2,5-chloropyrimidine;2,5-DichloropyriMidine 97+%;2,5-Dichloro-1,3-diazine;2,5-DichloropyriMidine 97+%, 5-DichloropyriMidine 97+%
• CAS NO: 22536-67-0
• Molecular Formula: C₄H₂Cl₂N₂
• Molecular Weight: 148.98
• EINECS: 1312995-182-4
• Product Categories: PYRIMIDINE;Pyrimidine Series;Pyridines, Pyrimidines, Purines and Pteredines;Chlorinated heterocyclic series;Building Blocks;C4 to C5;Chemical Synthesis;Halogenated Heterocycles;Heterocyclic Building Blocks;Pyrimidines;Heterocycle-Pyrimidine series
• Mol File: 22536-67-0.mol

Chemical Properties

• Melting Point: 57.0-57.5°C
• Boiling Point: 190°C
• Flash Point: 140°C
• Appearance: Off-white/Powder
• Density: 1.493
• Vapor Pressure: 0.0152mmHg at 25°C
• Refractive Index: 1.559
• Storage Temp.: Keep in dark place,Sealed in dry,Room Temperature
• PKA: -2.84±0.22(Predicted)
• Water Solubility: Slightly soluble in water.
• CAS DataBase Reference: 2,5-Dichloropyrimidine(CAS DataBase Reference)
• NIST Chemistry Reference: 2,5-Dichloropyrimidine(22536-67-0)
• EPA Substance Registry System: 2,5-Dichloropyrimidine(22536-67-0)

Safety Data

• Hazard Codes: C,N,Xn
• Statements: 22-41-50
• Safety Statements: 26-39-61
• RIDADR: UN 3077 9/PG 3
• WGK Germany: 2
• HazardClass: LACHRYMATOR, CORROSIVE
• PackingGroup: Ⅲ
• Hazardous Substances Data: 22536-67-0(Hazardous Substances Data)

Usage

Uses

Used in Agrochemical Industry:
2,5-Dichloropyrimidine is used as an important raw material and intermediate for the development of agrochemicals. Its chemical properties make it suitable for the synthesis of compounds that can be used as pesticides, herbicides, or other agricultural chemicals to enhance crop protection and yield.
Used in Pharmaceutical Industry:
In the pharmaceutical sector, 2,5-Dichloropyrimidine is utilized as a key intermediate in the synthesis of various drugs. Its unique structure allows for the creation of molecules with specific therapeutic properties, potentially leading to the development of new medications for treating various diseases and conditions.
Used in Dye Industry:
2,5-Dichloropyrimidine is also employed in the dyestuff field as a vital intermediate for the production of different types of dyes. Its chemical structure contributes to the development of dyes with specific color properties, which can be used in various applications such as textiles, plastics, and printing inks.

InChI:InChI=1/C4H2Cl2N2/c5-3-1-7-4(6)8-2-3/h1-2H

Synthetic route

(2-chloropyrimidin-5-yl)boronic acid (1003845-06-4) → 2,5-dichloropyrimidine (22536-67-0)

Conditions	Yield
With N-chloro-succinimide; copper(l) chloride In acetonitrile at 80℃; for 16h;	75%

5-chloropyrimidin-2-amine (5428-89-7) → 2,5-dichloropyrimidine (22536-67-0)

Conditions	Yield
With hydrogenchloride; sodium nitrite

5-chloropyrimidin-2-one (54326-16-8) → 2,5-dichloropyrimidine (22536-67-0)

Conditions	Yield
With trichlorophosphate

2-hydroxypyrimidine hydrochloride (38353-09-2) → 2,5-dichloropyrimidine (22536-67-0)

Conditions	Yield
With chlorine; N,N-dimethyl-aniline; trichlorophosphate Yield given. Multistep reaction;

2-hydroxy-5-chloropyrimidine (54326-16-8) → 2,5-dichloropyrimidine (22536-67-0)

Conditions	Yield
Stage #1: 5-chloro-2-hydroxypyrimidine With N,N-dimethyl-aniline; trichlorophosphate at 120℃; for 1h; Stage #2: With water at 0℃;
Stage #1: 5-chloro-2-hydroxypyrimidine With N,N-dimethyl-aniline; trichlorophosphate at 120℃; for 1h; Stage #2: With water
With trichlorophosphate In N,N-dimethyl-aniline at 120℃; for 1h; Inert atmosphere;	6 g

2,4,5-trichloropyrimidine (5750-76-5) → 2,5-dichloropyrimidine (22536-67-0)

Conditions	Yield
Stage #1: 2,4,5-trichloropyrimidine With hydrogen; palladium 10% on activated carbon In methanol at 50℃; for 2h; Stage #2: With sodium hydrogencarbonate In methanol; water at 20℃;
With acetic acid; zinc In tetrahydrofuran at 20℃; for 2h; Heating; Reflux;
With acetic acid; zinc In tetrahydrofuran for 2h; Reflux;
Stage #1: 2,4,5-trichloropyrimidine With acetic acid; zinc In tetrahydrofuran for 2h; Reflux; Stage #2: With sodium hydrogencarbonate; sodium hydroxide In dichloromethane; water pH=10;
With acetic acid; zinc In tetrahydrofuran at 20℃; Reflux;

2,5-dichloropyrimidine (22536-67-0) + sodium salt of ethyl cyanoacetate → (5-Chloro-pyrimidin-2-yl)-cyano-acetic acid ethyl ester (65364-65-0)

Conditions	Yield
at 70℃; for 3h;	100%

2,5-dichloropyrimidine (22536-67-0) + C26H28N2O3S → C30H29ClN4O3S

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In isopropyl alcohol Reflux;	100%

2,5-dichloropyrimidine (22536-67-0) + 1-((1r,4r)-4-((2-fluoro-4-(1H-tetrazol-1-yl)phenoxy)methyl)cyclohexyl)piperazine dihydrochloride → 5-chloro-2-(4-((1r,4r)-4-((2-fluoro-4-(1H-tetrazol-1-yl)phenoxy)methyl)cyclohexyl)piperazin-1-yl)pyrimidine

Conditions	Yield
With triethylamine In isopropyl alcohol at 80℃; for 3h;	97%

2,5-dichloropyrimidine (22536-67-0) + 5-bromo-1-(4,4,4-trifluorobutyl)indazol-7-ol → 5-bromo-7-(5-chloropyrimidin-2-yl)oxy-1-(4,4,4-trifluorobutyl)indazole

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 1h;	97%

2,5-dichloropyrimidine (22536-67-0) + hexan-1-amine (111-26-2) → 5-chloro-N-hexylpyrimidin-2-amine

Conditions	Yield
With potassium phosphate; (1,3,5-triaza-7-phosphaadamantan-1-ium-1-yl)butane-1-sulfonate; copper(II) acetate monohydrate In water at 30℃; for 22h; Schlenk technique; Inert atmosphere;	97%

2,5-dichloropyrimidine (22536-67-0) + tri-n-butyl(vinyl)tin (7486-35-3) → 2-chloro-4-vinylpyrimidine (131467-02-2)

Conditions	Yield
With 2-chloro-4-pyrimidine In 1,2-dichloro-ethane at 70℃; for 2h;	94%

2,5-dichloropyrimidine (22536-67-0) + sodium phenyl-methanolate (20194-18-7) → 2-benzyloxy-5-chloropyrimidine

Conditions	Yield
In benzyl alcohol Ambient temperature;	94%

2,5-dichloropyrimidine (22536-67-0) + 3-((1r,4r)-4-(piperidin-4-yloxy)cyclohexyloxy)pyrazine-2-carbonitrile hydrochloride → 3-((1r,4r)-4-(1-(5-chloropyrimidin-2-yl)piperidin-4-yloxy)cyclohexyloxy)pyrazine-2-carbonitrile

Conditions	Yield
With triethylamine In isopropyl alcohol at 120℃; for 3h; Microwave irradiation;	93.1%

N,N,N,N,N,N-hexamethylphosphoric triamide (680-31-9) + 2,5-dichloropyrimidine (22536-67-0) → 5-chloro-2-N,N-dimethylaminopyrimidine

Conditions	Yield
Heating;	92%

2,5-dichloropyrimidine (22536-67-0) + 1-butyn-4-ol (927-74-2) → 2-(but-3-ynyloxy)-5-chloropyrimidine (1356542-25-0)

Conditions	Yield
Stage #1: 3-Butyn-1-ol With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: 2,5-dichloropyrimidine In tetrahydrofuran at 20℃; for 17h; Inert atmosphere;	92%
Stage #1: 3-Butyn-1-ol With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: 2,5-dichloropyrimidine In tetrahydrofuran at 20℃; for 17h; Inert atmosphere;	92%
Stage #1: 3-Butyn-1-ol With sodium hydride In tetrahydrofuran at 0℃; for 1h; Stage #2: 2,5-dichloropyrimidine In tetrahydrofuran at 20℃;	57%

2,5-dichloropyrimidine (22536-67-0) + 1-(4,4,4-trifluorobutyl)indazol-7-ol → 7-(5-chloropyrimidin-2-yl)oxy-1-(4,4,4-trifluorobutyl)indazole

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 1h;	91%

2,5-dichloropyrimidine (22536-67-0) + 3-(4,4,4-trifluorobutyl)benzotriazol-4-ol → 7-(5-chloropyrimidin-2-yl)oxy-1-(4,4,4-trifluorobutyl)benzotriazole

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃;	91%

2,5-dichloropyrimidine (22536-67-0) + 1-(4,4,4-trifluorobutyl)-3-(trifluoromethyl)indazol-7-ol → 7-(5-chloropyrimidin-2-yl)oxy-1-(4,4,4-trifluorobutyl)-3-(trifluoromethyl)indazole

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 4h;	90%

Thiophene-2-thiol (7774-74-5) + 2,5-dichloropyrimidine (22536-67-0) → 2-(thien-2-yl)thio-5-chloropyrimidine

Conditions	Yield
With NaOEt	89%

pyrrolidine (123-75-1) + 2,5-dichloropyrimidine (22536-67-0) → 5-chloro-2-(pyrrolidin-1-yl)pyrimidine

Conditions	Yield
With 1,3-bis[(diphenylphosphino)propane]dichloronickel(II); N,N,N′,N′-tetramethyl-N″-tert-butylguanidine; 4-phenyl-N-methylpyridinium iodide; 4,4'-di-tert-butyl-2,2'-bipyridine; zinc In dimethyl sulfoxide at 80℃; for 8h; Reagent/catalyst; Inert atmosphere;	89%

2,5-dichloropyrimidine (22536-67-0) + (S)-3-((4-bromo-2-fluorophenoxy)methyl)pyrrolidine hydrochloride → (S)-2-(3-((4-bromo-2-fluorophenoxy)methyl)pyrrolidin-1-yl)-5-chloropyrimidine

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 150℃; for 3h; Solvent; Microwave irradiation;	88.2%
With triethylamine In N,N-dimethyl acetamide at 150℃; for 3h; Microwave irradiation;	88%

2,5-dichloropyrimidine (22536-67-0) + 1-propynyltributylstannane (64099-82-7) → 5-chloro-2-(prop-1-yn-1-yl)pyrimidine

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride In 1,4-dioxane at 80℃;	88%

2,5-dichloropyrimidine (22536-67-0) + 4-((1r,4r)-4-(piperidin-4-yloxy)cyclohexyloxy)nicotinonitrile dihydrochloride → 4-((1r,4r)-4-(1-(5-chloropyrimidin-2-yl)piperidin-4-yloxy)cyclohexyloxy)nicotinonitrile (1415818-51-7)

Conditions	Yield
With potassium carbonate In isopropyl alcohol at 100℃; for 4h; Microwave irradiation;	87.7%

morpholine (110-91-8) + 2,5-dichloropyrimidine (22536-67-0) → 4-(5-chloropyrimidin-2-yl)morpholine (124595-95-5)

Conditions	Yield
With potassium phosphate; (1,3,5-triaza-7-phosphaadamantan-1-ium-1-yl)butane-1-sulfonate; copper(II) acetate monohydrate In water at 30℃; for 22h; Schlenk technique; Inert atmosphere; chemoselective reaction;	87%

2,5-dichloropyrimidine (22536-67-0) + 4-hydroxy-3-(4,4,4-trifluorobutyl)-3H-isobenzofuran-1-one → 4-[(5-chloro-2-pyrimidinyl)oxy]-3-(4,4,4-trifluorobutyl)-1(3H)-isobenzofuranone

Conditions	Yield
With potassium phosphate In toluene at 110℃; for 3h;	86%

2,5-dichloropyrimidine (22536-67-0) + 4-chloro-1-(4,4,4-trifluorobutyl)indazol-7-ol → 4-chloro-7-(5-chloropyrimidin-2-yl)oxy-1-(4,4,4-trifluorobutyl)indazole

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 1h;	85%

2,5-dichloropyrimidine (22536-67-0) + 9-phenyl-3,3'-bicarbazole (1060735-14-9) → C34H21ClN4

Conditions	Yield
Stage #1: 9-phenyl-3,3'-bicarbazole With sodium hydride In N,N-dimethyl-formamide for 0.5h; Stage #2: 2,5-dichloropyrimidine In N,N-dimethyl-formamide at 20℃; for 4h;	84%

4-piperidinemethanol (6457-49-4) + 2,5-dichloropyrimidine (22536-67-0) → (1-(5-chloropyrimidin-2-yl)piperidin-4-yl)methanol

Conditions	Yield
With triethylamine In acetonitrile for 16h; Reflux;	82.4%
With triethylamine In acetonitrile for 16h; Reflux;	82.4%

2,5-dichloropyrimidine (22536-67-0) + 1-[4-[6-(aminomethyl)-2-methyl-pyrimidin-4-yl]oxyphenyl]-N-methyl-methanesulfonamide → 1-[4-[6-[[(5-chloropyrimidin-2-yl)amino]methyl]-2-methyl-pyrimidin-4-yl]oxyphenyl]-N-methyl-methanesulfonamide

Conditions	Yield
With potassium fluoride In dimethyl sulfoxide at 120℃; for 2h;	82%

3-(piperidin-4-yl)propan-1-ol (7037-49-2) + 2,5-dichloropyrimidine (22536-67-0) → 3-(1-(5-chloropyrimidin-2-yl)piperidin-4-yl)propan-1-ol (1204310-31-5)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 60℃;	82%

2,5-dichloropyrimidine (22536-67-0) + (R)-3-aminopyrrolidine-1-carboxylic acid tert-butyl ester (147081-49-0) → (R)-tert-butyl 3-((5-chloropyrimidin-2-yl)amino)pyrrolidine-1-carboxylate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 30℃;	81%

4-ethylpiperazine (5308-25-8) + 2,5-dichloropyrimidine (22536-67-0) → 5-chloro-2-(4-{2-[(5-chloropyrimidin-2-yl)sulfanyl]ethyl}piperazin-1-yl)pyrimidine

Conditions	Yield
With sodium sulfide In toluene at 40℃; for 12h;	80%

2,5-dichloropyrimidine (22536-67-0) + sodium methylate (124-41-4) → 2-methoxy-5-chloropyrimidine (38373-44-3)

Conditions	Yield
In methanol at 20℃; for 1h; Sealed tube; regioselective reaction;	80%

2,5-dichloropyrimidine (22536-67-0) + (R)-3-hydroxy-1-(piperidin-4-yl)pyrrolidin-2-one hydrochloride → (R)-1-(1-(5-chloropyrimidin-2-yl)piperidin-4-yl)-3-hydroxypyrrolidin-2-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 4h;	80%

2,5-dichloropyrimidine (22536-67-0) + phenylboronic acid (98-80-6) → 2,5-diphenylpyrimidine (29134-16-5)

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In 1,4-dioxane at 90℃; Suzuki coupling;	79%
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In 1,4-dioxane at 90℃;	79%

Upstream product

• 5428-89-7 5-chloropyrimidin-2-amine 
• 54326-16-8 5-chloropyrimidin-2-one 
• 38353-09-2 2-hydroxypyrimidine hydrochloride 
• 54326-16-8 5-chloro-2-hydroxypyrimidine 
• 5750-76-5 2,4,5-trichloropyrimidine 
• 1003845-06-4 (2-chloropyrimidin-5-yl)boronic acid 

Downstream Products

• 38373-44-3 5-chloro-2-methoxypyrimidine 
• 857011-22-4 [2-(5-chloro-pyrimidin-2-yloxy)-ethyl]-dimethyl-amine 
• 34772-97-9 5-chloropyrimidine-2(1H)-thione 
• 45715-16-0 5-chloro-N-methylpyrimidin-2-amine 
• 289-95-2 PYRIMIDINE 
• 1606-49-1 1,4,5,6-tetrahydropyrimidine 
• 17180-94-8 5-chloropyrimidine 
• 111986-56-2 4-((5-chloropyrimidin-2-yl)oxy)-3-methylaniline 
• 110965-58-7 4-((5-chloropyrimidin-2-yl)oxy)-3-fluoroaniline 
• 105355-37-1 3-chloro-4-((5-chloropyrimidin-2-yl)oxy)aniline 
• 112002-80-9 4-(5-Chloro-pyrimidin-2-yloxy)-3-methoxy-phenylamine 
• 131467-02-2 2-chloro-4-vinylpyrimidine 
• 80016-42-8 2-allyloxy-5-chloropyrimidine 
• 79685-95-3 2-phenylthio-5-chloropyrimidine 

Relevant articles and documents

Structure Analysis Restrained by ab Initio Calculations: The Molecular Structure of 2,5-Dichloropyrimidine in Gaseous and Crystalline Phases

A new method to obtain improved structural parametes by supplementing gas-phase electron diffraction (GED) data with restrains based on the results of ab initio calculations is proposed.The procedure involves the use of ab initio parameters with estimated uncertainties as additional observations; this allows previously fixed parameters to refine, with all geometrical parameters included in the final refinement.The refinement of the molecular structure of 2,5-dichloropyrimidine is used as an example to illustrate the principle of this technique.In this simple case, the effects are not very great, but this new approach allowed refinement of all structural parameters.The nine independent structural parameters (rα structure) were found to be: r = 139.3(11) pm, r = 133.2(4) pm, r = 132.5(5) pm, r = 172.2(3) pm, r = 172.8(3) pm, r = 109.9(12) pm, = 127.9(4) deg, = 116.3(7) deg, and = 117.2(5) deg.All structural parameters were found to be in good agreement with both ab initio and crystallographic values, which are presented for comparison.

NOVEL COMPOUNDS AS GPR119 AGONISTS

The present invention relates to novel compounds of formula (I) as GPR119 agonist, composition compositions containing such compounds and method of preparation thereof.

Discovery of BI 207524, an indole diamide NS5B thumb pocket 1 inhibitor with improved potency for the potential treatment of chronic hepatitis C virus infection

The development of interferon-free regimens for the treatment of chronic HCV infection constitutes a preferred option that is expected in the future to provide patients with improved efficacy, better tolerability, and reduced risk for emergence of drug-resistant virus. We have pursued non-nucleoside NS5B polymerase allosteric inhibitors as combination partners with other direct acting antivirals (DAAs) having a complementary mechanism of action. Herein, we describe the discovery of a potent follow-up compound (BI 207524, 27) to the first thumb pocket 1 NS5B inhibitor to demonstrate antiviral activity in genotype 1 HCV infected patients, BILB 1941 (1). Cell-based replicon potency was significantly improved through electronic modulation of the pKa of the carboxylic acid function of the lead molecule. Subsequent ADME-PK optimization lead to 27, a predicted low clearance compound in man. The preclinical profile of inhibitor 27 is discussed, as well as the identification of a genotoxic metabolite that led to the discontinuation of the development of this compound.

SUBSTITUTED CYCLOPROPYL COMPOUNDS USEFUL AS GPR119 AGONISTS

Substituted cyclopropyl compounds of the formula (I): and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing type 2 diabetes and similar conditions. The compounds are useful as agonists of the G-protein coupled receptor GPR-119. Pharmaceutical compositions and methods of treatment are also included

SUBSTITUTED CYCLOPROPYL COMPOUNDS USEFUL AS GPR119 AGONISTS

Substituted cyclopropyl compounds of the formula I: and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing type 2 diabetes and similar conditions. The compounds are useful as agonists of the G-protein coupled receptor GPR-119. Pharmaceutical compositions and methods of treatment are also included.

SUBSTITUTED CYCLOPROPYL COMPOUNDS, COMPOSITIONS CONTAINING SUCH COMPOUNDS AND METHODS OF TREATMENT

Substituted cyclopropyl compounds of the formula I: are disclosed as useful for treating or preventing type 2 diabetes and similar conditions. Pharmaceutically acceptable salts are included as well. The compounds are useful as agonists of the g-protein coupled receptor GPR-119.

SUBSTITUTED CYCLOPROPYL COMPOUNDS, COMPOSITIONS CONTAINING SUCH COMPOUNDS AND METHODS OF TREATMENT

Substituted cyclopropyl compounds of formula (I) are disclosed as useful for treating or preventing type 2 diabetes and similar conditions. Pharmaceutically acceptable salts and solvates are included as well. The compounds are useful as agonists of the g-protein coupled receptor GPR-119.

BIPIPERIDINYL COMPOUNDS, COMPOSITIONS CONTAINING SUCH COMPOUNDS AND METHODS OF TREATMENT

Bipiperidinyl compounds of the formula I, are disclosed as useful for treating or preventing type 2 diabetes and similar conditions. Pharmaceutically acceptable salts and solvates are included as well. The compounds are useful as agonists of the g-protein coupled receptor GPR-119.

VIRAL POLYMERASE INHIBITORS

The present invention relates to compounds represented by formula (I) wherein A, B, D, E, R2, R3, R4, R5, R6, R9, a, b, d and e are as defined herein, their salt or ester and pharmaceutical compositions thereof useful in the treatment of hepatitis C viral (HCV) infection. Said compounds were found to have inhibitory activity against HCV polymerase, especially as inhibitors of HCV NS5B polymerase

VIRAL POLYMERASE INHIBITORS

A compound, represented by formula (I) or an enantiomer, diastereoisomer or tautomer thereof : wherein either A or B is nitrogen and the other B or A is C, and the radicals R1, R2, R3, R5, R6, R7, R9, and R10 are as defined herein, or a salt, ester or derivative thereof as viral polymerase inhibitors. The compound is used as an inhibitor of RNA dependent RNA polymerases, particulary those viral polymerases within the Flaviviridae family, more particulary to HCV polymerase.