5750-76-5

Basic information

• Product Name: 2,4,5-Trichloropyrimidine
• Synonyms: 2,4,5-TRICHLOROPYRIMIDINE;2,5,6-TRICHLOROPYRIMIDINE;2,4,5-TRICHLOROPYRIMIDINE, 97+%;2,4,5-Trichloropyrimidine, 99+%;2,4,5-Trichloropyrimidine ,98%;2,4,5-Trichloro-1,3-diazine;2,4,5-three chloropyriMidine;2,4,5-TrichloropyriMidine 99%
• CAS NO: 5750-76-5
• Molecular Formula: C₄HCl₃N₂
• Molecular Weight: 183.42
• EINECS: 1312995-182-4
• Product Categories: Heterocycles;pharmacetical;Halides;Pyrazines, Pyrimidines & Pyridazines;Pyrimidine;Pyrimidine series;Halogenated;Organohalides;Pyrazines, Pyrimidines & Pyridazines;Building Blocks;Halogenated Heterocycles;Heterocyclic Building Blocks;Pyrimidines;PyrimidinesHeterocyclic Building Blocks;Heterocycle-Pyrimidine series
• Mol File: 5750-76-5.mol
• Article Data: 21

Chemical Properties

• Boiling Point: 84°C 1mm
• Flash Point: >230 °F
• Appearance: Colorless to pale yellow liquid
• Density: 1.6001 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.0221mmHg at 25°C
• Refractive Index: n20/D 1.574(lit.)
• Storage Temp.: Inert atmosphere,Store in freezer, under -20°C
• PKA: -4.26±0.29(Predicted)
• Water Solubility: Not miscible or difficult to mix in water.
• BRN: 4449
• CAS DataBase Reference: 2,4,5-Trichloropyrimidine(CAS DataBase Reference)
• NIST Chemistry Reference: 2,4,5-Trichloropyrimidine(5750-76-5)
• EPA Substance Registry System: 2,4,5-Trichloropyrimidine(5750-76-5)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• RIDADR: 3267
• WGK Germany: 3
• HazardClass: 8
• PackingGroup: III
• Hazardous Substances Data: 5750-76-5(Hazardous Substances Data)

Usage

Chemical Properties

Colorless to pale yellow liquid

Uses

2,4,5-Trichloropyrimidine is used in the synthesis of potent and selective anaplastic lymphoma kinase (ALK-5) inhibitors, used as an anti-tumor treatment. Also used in the synthesis of EGFR inhibitors.

InChI:InChI=1/C4HCl3N2/c5-2-1-8-4(7)9-3(2)6/h1H

Synthetic route

5-chlorouracil (1820-81-1) → 2,4,5-trichloropyrimidine (5750-76-5)

Conditions	Yield
With phosphorus pentachloride; trichlorophosphate Neat (no solvent); Heating / reflux;	95%
With phosgene; Triphenylphosphine oxide In nitrobenzene at -5 - 125℃; for 0.833333h; Inert atmosphere;	93%
With N,N-diethylaniline; trichlorophosphate at 110℃; for 24h;	81%

2,4-dihydroxy-5-chloropyrimidine (1820-81-1) → 2,4,5-trichloropyrimidine (5750-76-5)

Conditions	Yield
With dmap; thionyl chloride; bis(trichloromethyl) carbonate for 10h; Reflux; Green chemistry;	91%
With pyridine; trichlorophosphate at 160℃; for 2h; Autoclave; neat (no solvent);	89%

2-cyanoethyl isocyanide dichloride → 2,4,5-trichloropyrimidine (5750-76-5)

Conditions	Yield
With hydrogenchloride In chloroform; chlorine
With hydrogenchloride; thionyl chloride In chlorine

disulfur dichloride (10025-67-9) + sulphur dichloride + (2-cyanoethyl)-methyl-dithiocarbamic acid methyl ester → 2,4,5-trichloropyrimidine (5750-76-5)

4-fluoro-N-methylaniline (459-59-6) + 2,4,5-trichloropyrimidine (5750-76-5) → 2,5-dichloro-N-(4-fluorophenyl)-N-methylpyrimidin-4-amine (1341200-86-9)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In isopropyl alcohol for 12h; Reflux;	100%

4-difluoromethoxyaniline (22236-10-8) + 2,4,5-trichloropyrimidine (5750-76-5) → 2,5-dichloro-N-(4-(difluoromethoxy)phenyl)pyrimidin-4-amine (1341200-83-6)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In isopropyl alcohol for 12h; Reflux;	100%

4-fluoroboronic acid (1765-93-1) + 2,4,5-trichloropyrimidine (5750-76-5) → 2,5-dichloro-4-(4-fluorophenyl)pyrimidine (1341200-89-2)

Conditions	Yield
With palladium diacetate; sodium carbonate; triphenylphosphine In tetrahydrofuran; water for 12h; Suzuki coupling; Reflux;	100%

2,4,5-trichloropyrimidine (5750-76-5) + 4-fluoroaniline (371-40-4) → 2,5-dichloro-N-(4-fluorophenyl)pyrimidine-4-amine (280582-13-0)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In isopropyl alcohol for 12h; Reflux;	100%
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃;	85%
Stage #1: 2,4,5-trichloropyrimidine With tetra-(n-butyl)ammonium iodide In dimethyl sulfoxide at 20℃; Stage #2: 4-fluoroaniline With triethylamine In dimethyl sulfoxide at 20℃; for 3h;	65%
With sodium carbonate In ethanol at 20℃; for 16h;	57%
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃;	57%

5-aminohexahydrocyclopenta[c]pyrrole-2(1H)-carboxylic acid tert-butyl ester + 2,4,5-trichloropyrimidine (5750-76-5) → tert-butyl 5-((2,5-dichloropyrimidin-4-yl)amino)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate

Conditions	Yield
With triethylamine In ethanol at 20℃;	100%
With triethylamine In ethanol at 20℃;	100%
With triethylamine In ethanol at 20℃;	100%

(S)-10-amino-2-cyclopropyl-3,3-difluoro-7-methyl-1,2,3,4-tetrahydro-[1,4]oxazepino[2,3-c]quinolin-6(7H)-one + 2,4,5-trichloropyrimidine (5750-76-5) → (S)-2-cyclopropyl-10-((2,5-dichloropyrimidin-4-yl)amino)-3,3-difluoro-7-methyl-1,2,3,4-tetrahydro-[1,4]oxazepino[2,3-c]quinolin-6(7H)-one

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one at 140℃; for 1h; Inert atmosphere; Microwave irradiation; Sealed tube;	100%
With N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one at 140℃; for 1h; Inert atmosphere; Microwave irradiation;	88%

2,2,2-trifluoroethanol (75-89-8) + 2,4,5-trichloropyrimidine (5750-76-5) → 2,5-dichloro-4-(2,2,2-trifluoroethoxy)pyrimidine

Conditions	Yield
With potassium carbonate at 20℃; for 2h;	100%

2-fluoro-6-nitroaniline (17809-36-8) + 2,4,5-trichloropyrimidine (5750-76-5) → 2,5-dichloro-N-(2-fluoro-6-nitrophenyl)pyrimidin-4-amine

Conditions	Yield
Stage #1: 2-fluoro-6-nitroaniline With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.5h; Stage #2: 2,4,5-trichloropyrimidine In N,N-dimethyl-formamide; mineral oil at 0℃; for 2h;	100%

2,4,5-trichloropyrimidine (5750-76-5) + aniline (62-53-3) → 4-Anilino-2,5-dichloropyrimidine (280581-45-5)

Conditions	Yield
With potassium phosphate; TPGS-750-M In water at 20℃; for 24h; Inert atmosphere;	99%
With N-ethyl-N,N-diisopropylamine In isopropyl alcohol for 12h; Reflux;	92%
Stage #1: 2,4,5-trichloropyrimidine With tetra-(n-butyl)ammonium iodide In dimethyl sulfoxide at 20℃; Stage #2: aniline With triethylamine In dimethyl sulfoxide at 20℃; for 3h;	89%

2,4,5-trichloropyrimidine (5750-76-5) + tert-butyl ((1r,4r)-4-(aminomethyl)cyclohexyl)carbamate (177583-27-6) → {4-[(2,5-dichloro-pyrimidin-4-ylamino)-methyl]-cyclohexyl}-carbamic acid tert-butyl ester (874822-31-8)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In ethanol at 40℃; for 1h;	99%

2,4,5-trichloropyrimidine (5750-76-5) + 4-chloro-aniline (106-47-8) → 2,5-dichloro-N-(4-chlorophenyl)pyrimidin-4-amine (1341200-80-3)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In isopropyl alcohol for 12h; Reflux;	99%
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 16h;	61%
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃;	61%

(R)-1-(4-methoxyphenyl)ethylamine (6298-96-0, 22038-86-4, 35600-82-9, 41851-59-6) + 2,4,5-trichloropyrimidine (5750-76-5) → (S)-2,5-dichloro-N-(1-(4-methoxyphenyl)ethyl)pyrimidin-4-amine

Conditions	Yield
With potassium phosphate; TPGS-750-M In water at 20℃; for 20h; Inert atmosphere;	99%

2,4,5-trichloropyrimidine (5750-76-5) + phenol (108-95-2) → 2,5-dichloro-4-phenoxypyrimidine

Conditions	Yield
With potassium carbonate In acetone at 20℃; for 6h;	99%
Stage #1: 2,4,5-trichloropyrimidine With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.25h; Inert atmosphere; Stage #2: phenol In N,N-dimethyl-formamide at 20℃; for 3h; Inert atmosphere;	92%
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 4h;

3-((5-methyl-4-nitro-1H-pyrazol-3-yl)oxy)propan-1-amine hydrochloride + 2,4,5-trichloropyrimidine (5750-76-5) → 2,5-dichloro-N-(3-((5-methyl-4-nitro-1H-pyrazol-3-yl)oxy)propyl)pyrimidin-4-amine

Conditions	Yield
Stage #1: 3-((5-methyl-4-nitro-1H-pyrazol-3-yl)oxy)propan-1-amine hydrochloride With N-ethyl-N,N-diisopropylamine In isopropyl alcohol at 0℃; for 0.166667h; Inert atmosphere; Stage #2: 2,4,5-trichloropyrimidine In isopropyl alcohol at 0 - 20℃; Inert atmosphere;	99%

sodium thiomethanolate + 2,4,5-trichloropyrimidine (5750-76-5) → 2,5-dichloro-4-(methylthio)pyrimidine (1245830-98-1)

Conditions	Yield
In tetrahydrofuran; water at 0 - 20℃; for 4h;	99%

4-fluoro-2-{[(oxan-2-yl)oxy]methyl}-1-(propan-2-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzimidazole + 2,4,5-trichloropyrimidine (5750-76-5) → 6-(2,5-dichloropyrimidin-4-yl)-4-fluoro-2-{[(oxan-2-yl)oxy]methyl}-1-(propan-2-yl)-1H-benzimidazole

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane; water at 90℃; for 16h; Inert atmosphere;	99%

cis-2-(3a,6a-dimethyl-1-oxohexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)acetamide + 2,4,5-trichloropyrimidine (5750-76-5) → cis-2-(5-(2,5-dichloropyrimidin-4-yl)-3a,6a-dimethyl-1-oxohexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)acetamide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile at 50℃; for 12h; Inert atmosphere;	99%

2,4,5-trichloropyrimidine (5750-76-5) + methylamine (74-89-5) → 2-chloro-5-chloro-N-methylpyrimidin-4-amine (940927-35-5)

Conditions	Yield
In tetrahydrofuran at 0 - 20℃; regioselective reaction;	98%
In tetrahydrofuran at 0 - 20℃; for 6h; regioselective reaction;	85%
In ethanol at 0℃;	83%

2-(2-ethynylphenyl)propanamide (1566543-62-1) + 2,4,5-trichloropyrimidine (5750-76-5) → 2-(2-((2,5-dichloropyrimidin-4-yl)ethynyl)phenyl)propanamide (1566543-95-0)

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In 1,4-dioxane at 60℃; for 2.5h; Inert atmosphere;	98%

2,4,5-trichloropyrimidine (5750-76-5) + naphthalen-2-ylamine (91-59-8) → 2,5-dichloro-N-(naphthalene-2-yl)pyrimidin-4-amine

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In isopropyl alcohol for 2h; Reflux;	98%
With sodium carbonate In ethanol at 20℃; regioselective reaction;	88%
With sodium carbonate In ethanol at 20℃;	88%
With sodium carbonate In ethanol	88%
With N-ethyl-N,N-diisopropylamine In isopropyl alcohol for 3h; Heating;	79.6%

5-(1,1-dioxothiomorpholin-4-yl)pentylamine + 2,4,5-trichloropyrimidine (5750-76-5) → N-(2,5-dichloropyrimidin-4-yl)-5-(1,1-dioxothiomorpholin-4-yl)pentylamine

Conditions	Yield
With triethylamine In ethanol at 70℃; for 4h;	98%

4-fluoro-1-isopropyl-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)-1H-benzo[d]imidazole (1231930-37-2) + 2,4,5-trichloropyrimidine (5750-76-5) → 6-(2,5-dichloropyrimidin-4-yl)-4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazole

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane; water at 90℃; for 16h; Inert atmosphere;	98%
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In water; N,N-dimethyl-formamide at 60℃; for 2h; Inert atmosphere;	31%

4-(4-amino-5-isopropoxy-2-methylphenyl)-piperidine-1-carboxylic acid tert-butyl ester (1032903-63-1) + 2,4,5-trichloropyrimidine (5750-76-5) → 4-(4-((4,5-dichloropyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidine-1-carboxylic acid tert-butyl ester

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In isopropyl alcohol at 80℃; for 24h; Reagent/catalyst; Temperature; Solvent; Inert atmosphere;	97.9%

2,4,5-trichloropyrimidine (5750-76-5) + (R)-2-amino-2-(4-fluorophenyl)ethanol (174770-74-2) → (2R)-2-[(2,5-dichloropyrimidin-4-yl)amino]-2-(4-fluorophenyl)ethanol

Conditions	Yield
With triethylamine In ethanol at 20℃; for 12h;	97%

5-methoxy-1H-pyrazol-3-amine (41307-23-7) + 2,4,5-trichloropyrimidine (5750-76-5) → 2,5-dichloro-N-(5-methoxy-1H-pyrazol-3-yl)pyrimidin-4-amine (915720-77-3)

Conditions	Yield
With triethylamine In ethanol at 18 - 25℃; for 12h; regioselective reaction;	97%
With triethylamine In ethanol at 18 - 25℃; for 12h;
With triethylamine In ethanol at 20℃; for 12h;

2,4,5-trichloropyrimidine (5750-76-5) + Cyclopropylamine (765-30-0) → 2,5-dichloro-N-cyclopropylpyrimidin-4-amine (1050602-55-5)

Conditions	Yield
With potassium carbonate In acetonitrile at -10 - 20℃;	97%
In ethanol at 0℃;	63%
With N-ethyl-N,N-diisopropylamine for 12h; Reflux;	45%

morpholine (110-91-8) + 2,4,5-trichloropyrimidine (5750-76-5) → 4-(2,5-dichloropyrimidin-4-yl)morpholine (1215126-57-0)

Conditions	Yield
With potassium phosphate monohydrate; C64H118O20 In water at 45℃; for 3h; Reagent/catalyst;	97%
With potassium phosphate; TPGS-750-M In water at 20℃; for 20h; Inert atmosphere;	86%
In ethanol at 0℃; for 3h;	70%
With triethylamine In tetrahydrofuran at 25℃; for 1h; Inert atmosphere;

2,4,5-trichloropyrimidine (5750-76-5) + 3,5-Dimethoxyaniline (10272-07-8) → 2,5-dichloro-N4-(3,5-dimethoxyphenyl)pyrimidin-4-amine

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In isopropyl alcohol for 2h; Reflux;	97%
With N-ethyl-N,N-diisopropylamine In isopropyl alcohol for 0.166667h; Reflux;	85%
With N-ethyl-N,N-diisopropylamine In isopropyl alcohol for 0.166667h; Reflux;	85%

2,4,5-trichloropyrimidine (5750-76-5) + 3,4,5-Trimethoxyaniline (24313-88-0) → 2,5-dichloro-N4-(3,4,5-trimethoxyphenyl)pyrimidin-4-amine

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In isopropyl alcohol for 14h; Reflux;	97%
With N-ethyl-N,N-diisopropylamine In isopropyl alcohol for 14h; Reflux;	97%
With N-ethyl-N,N-diisopropylamine In isopropyl alcohol for 2h; Reflux;	32%

3-fluoro-4-methoxyaniline (366-99-4) + 2,4,5-trichloropyrimidine (5750-76-5) → 2,5-dichloro-N-(3-fluoro-4-methoxyphenyl)pyrimidin-4-amine

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In isopropyl alcohol for 2h; Reflux;	97%

Upstream product

• 10025-67-9 disulfur dichloride 
• 1820-81-1 2,4-dihydroxy-5-chloropyrimidine 
• 1820-81-1 5-chlorouracil 

Downstream Products

• 269055-74-5 4-[(4,5-dichloro-2-pyrimidinyl)amino]benzonitrile 
• 5750-74-3 2,5-dichloro-4-methoxypyrimidine 
• 122372-10-5 2,5-dichloro-4-phenylpyrimidine 
• 937366-57-9 3-(2,5-dichloropyrimidine-4-yl)-1H-indole 
• 335592-59-1 4-[4-(1-tert-butoxycarbonylamino-1-methylethyl)phenyl]-2,5-dichloropyrimidine 
• 663611-49-2 methyl 4-(2,5-dichloropyrimidin-4-yl)benzoate 
• 761440-08-8 2-[(2,5-dichloropyrimidin-4-yl)amino]-N-methyl-benzamide 
• 860624-17-5 1-(2,5-dichloro-pyrimidin-4-yl)-piperidine-4-carboxylic acid [1-(3-chloro-phenyl)-2-hydroxy-ethyl]-amide 
• 874822-31-8 {4-[(2,5-dichloro-pyrimidin-4-ylamino)-methyl]-cyclohexyl}-carbamic acid tert-butyl ester 
• 358978-09-3 2,5-Dichloro-4-(4-methoxy-phenoxy)-pyrimidine 
• 543712-81-8 2,5-dichloro-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine 
• 1042434-89-8 2-[(2,5-dichloro-4-pyrimidinyl)amino]-4,5-difluorobenzamide 
• 1022947-10-9 ethyl 2-[(2,5-dichloro-4-pyrimidinyl)amino]benzoate 
• 1042434-80-9 2-((2,5-dichloropyrimidin-4-yl)amino)-N,N-dimethylbenzamide 

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