37552-81-1

Basic information

• Product Name: 4-Chloro-6-trifluoromethylpyrimidine
• Synonyms: PYRIMIDINE, 4-CHLORO-6-(TRIFLUOROMETHYL)-;IFLAB-BB F2124-0884;4-CHLORO-6-TRIFLUOROMETHYLPYRIMIDINE;6-Chloro-4-(trifluoromethyl)pyrimidine;4-CHLORO-6-(TRIFLUOROMETHYL)PYRIMIDINE ,98%;4-chloro-6-trifluorMethylpyriMidine;4-Chloro-6-(trifluoromethyl)-1,3-diazine
• CAS NO: 37552-81-1
• Molecular Formula: C₅H₂ClF₃N₂
• Molecular Weight: 182.53
• EINECS: 1312995-182-4
• Product Categories: Pyrimidine series;Pyrimidines;Pyrimidine;Boronic Acid;Heterocyclic Compounds;Fluorine series;alkyl chloride
• Mol File: 37552-81-1.mol

Chemical Properties

• Melting Point: -53--52 °C
• Boiling Point: 166.912 °C at 760 mmHg
• Flash Point: 54.747 °C
• Appearance: Colorless to pale yellow/Liquid
• Density: 1.504 g/cm³
• Vapor Pressure: 2.3mmHg at 25°C
• Refractive Index: 1.445
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• PKA: -4.62±0.18(Predicted)
• CAS DataBase Reference: 4-Chloro-6-trifluoromethylpyrimidine(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Chloro-6-trifluoromethylpyrimidine(37552-81-1)
• EPA Substance Registry System: 4-Chloro-6-trifluoromethylpyrimidine(37552-81-1)

Safety Data

• Statements: 36/37/38
• Safety Statements: 26-36/37/39
• Hazardous Substances Data: 37552-81-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
4-Chloro-6-trifluoromethylpyrimidine is used as a key building block for the synthesis of various pharmaceuticals due to its ability to enhance the biological activity of the resulting compounds. Its presence in the molecular structure can improve the potency, selectivity, and pharmacokinetic properties of the final drug products.
Used in Agrochemical Industry:
In the agrochemical sector, 4-Chloro-6-trifluoromethylpyrimidine is utilized as an intermediate in the development of new pesticides and other agrochemicals. Its unique chemical properties allow for the creation of compounds with improved efficacy and selectivity in controlling pests and diseases in agriculture.
Used in Organic Synthesis:
4-Chloro-6-trifluoromethylpyrimidine is employed as a versatile intermediate in organic synthesis, enabling the production of a broad range of organic compounds with diverse applications. Its reactivity and functional group compatibility make it a valuable component in the synthesis of complex organic molecules.
Used in Medicinal Chemistry Research and Development:
4-Chloro-6-trifluoromethylpyrimidine is used as a valuable chemical in research and development within the field of medicinal chemistry. It aids in the discovery and optimization of new drug candidates, contributing to the advancement of therapeutic agents with novel mechanisms of action and improved therapeutic profiles.

InChI:InChI=1/C5H2ClF3N2/c6-4-1-3(5(7,8)9)10-2-11-4/h1-2H

Synthetic route

4-trifluoromethyl-1,6-dihydropyrimidine-6-oxide (1546-78-7) → 4-chloro-6-(trifluoromethyl)pyrimidine (37552-81-1)

Conditions	Yield
With trichlorophosphate for 2h; Heating;	73%
With thionyl chloride; N,N-dimethyl-formamide In toluene at 80℃; for 4h;

4-hydroxy-6-trifluoromethylpyrimidine (1546-78-7) → 4-chloro-6-(trifluoromethyl)pyrimidine (37552-81-1)

Conditions	Yield
With quinoline; trichlorophosphate In toluene at 100℃; for 5h;	21.6%
With trichlorophosphate for 2h; Heating / reflux;
With quinoline; trichlorophosphate In toluene at 100℃; for 5h;

P,P-dichlorophenylphosphine oxide (824-72-6) + 4-trifluoromethyl-1,6-dihydropyrimidine-6-oxide (1546-78-7) → 4-chloro-6-trifluoropyrimidine + 4-chloro-6-(trifluoromethyl)pyrimidine (37552-81-1)

4-chloro-6-(trifluoromethyl)pyrimidine (37552-81-1) → 4-amino-6-(trifluoromethyl)pyrimidine (672-41-3)

Conditions	Yield
With ammonia In water; acetonitrile at 25℃; for 12h;	98%
With ammonia In methanol at 120℃; for 0.0833333h; Microwave irradiation;
With ammonia In methanol at 70℃; for 15h; Sealed tube;	920 mg
With ammonia In methanol at 25℃; for 12h;

(piperidin-4-yl)carbamic acid tert-butyl ester (73874-95-0) + 4-chloro-6-(trifluoromethyl)pyrimidine (37552-81-1) → tert-butyl 1-(6-(trifluoromethyl)pyrimidin-4-yl)piperidin-4-ylcarbamate (1329672-93-6)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one for 0.5h;	92%
With N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one for 0.5h;	92%

(R)-tert-butyl 2-(4-aminophenyl)morpholine-4-carboxylate (1260220-42-5) + 4-chloro-6-(trifluoromethyl)pyrimidine (37552-81-1) → (R)-tert-butyl 2-(4-(6-trifluoromethylpyrimidin-4-ylamino)phenyl)moipholine-4-carboxylate (1400997-86-5)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In ISOPROPYLAMIDE at 80℃;	89%

tert-butyl (2S)-2-(4-aminophenyl)morpholine-4-carboxylate (1260220-43-6) + 4-chloro-6-(trifluoromethyl)pyrimidine (37552-81-1) → (R)-tert-butyl 2-(4-(6-trifluoromethylpyrimidin-4-ylamino)phenyl)moipholine-4-carboxylate (1400997-86-5)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In ISOPROPYLAMIDE at 80℃;	89%

2,2-dimethylpropylamine (5813-64-9) + 4-chloro-6-(trifluoromethyl)pyrimidine (37552-81-1) → N-neopentyl-6-(trifluoromethyl)pyrimidin-4-amine

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 2h; Inert atmosphere;	88%

4-chloro-6-(trifluoromethyl)pyrimidine (37552-81-1) → 4-hydrazinyl-6-(trifluoromethyl)pyrimidine

Conditions	Yield
With hydrazine hydrate In ethanol at 20℃; for 2h;	88%

2-((1H-indol-3-yl)methyl)-2,7-diazaspiro[4.4]nonan-1-one (1383575-65-2) + 4-chloro-6-(trifluoromethyl)pyrimidine (37552-81-1) → 2-((1H-indol-3-yl)methyl)-7-(6-(trifluoromethyl)pyrimidin-4-yl)-2,7-diazaspiro[4.4]nonan-1-one (1383574-27-3)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine at 190℃; for 2h; Inert atmosphere; Microwave irradiation;	72%
With N-ethyl-N,N-diisopropylamine In acetonitrile at 190℃; for 2h; Inert atmosphere; microwave irradiation;	72%

methanol (67-56-1) + carbon monoxide (201230-82-2) + 4-chloro-6-(trifluoromethyl)pyrimidine (37552-81-1) → methyl 6-(trifluoromethyl)pyrimidine-4-carboxylate

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate at 70℃; for 6h; Inert atmosphere;	69.6%

1-(2-trifluoromethylindol-5-yl)methylamine (1192152-66-1) + 4-chloro-6-(trifluoromethyl)pyrimidine (37552-81-1) → 6-(trifluoromethyl)-N-{[2-(trifluoromethyl)-1H-indol-5-yl]methyl}pyrimidin-4-amine (1289105-95-8)

Conditions	Yield
With triethylamine for 5h; Reflux;	68%
With potassium carbonate In dimethyl sulfoxide at 130℃; for 1h; Microwave irradiation;

(S)-tert-butyl 3-methyl-2-oxoimidazolidine-4-carboxylate (845543-47-7) + 4-chloro-6-(trifluoromethyl)pyrimidine (37552-81-1) → 1,1-dimethylethyl 3-methyl-2-oxo-1-[6-(trifluoromethyl)-4-pyrimidinyl]-4-imidazolidinecarboxylate

Conditions	Yield
With caesium carbonate; tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane Heating / reflux;	67.5%

piperazine (110-85-0) + 4-chloro-6-(trifluoromethyl)pyrimidine (37552-81-1) → 4-piperazin-1-yl-6-(trifluoromethyl)pyrimidine (845616-55-9)

Conditions	Yield
With triethylamine In DMF (N,N-dimethyl-formamide) at 100℃; for 5h;	56.6%

(4-(3-phenylpropyl)piperidin-4-yl)methanol hydrochloride + 4-chloro-6-(trifluoromethyl)pyrimidine (37552-81-1) → (4-(3-phenylpropyl)-1-(6-(trifluoromethyl)pyrimidin-4-yl)piperidin-4-yl)methanol

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide at 120℃; for 24h; Sealed tube;	55%

(3-(3-phenylpropyl)piperidin-3-yl)methanol + 4-chloro-6-(trifluoromethyl)pyrimidine (37552-81-1) → (3-(3-phenylpropyl)-1-(6-(trifluoromethyl)pyrimidin-4-yl)piperidin-3-yl)methanol

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide at 120℃; for 17.4h; Sealed tube;	45%

(Methylsulfonyl)essigsaeure-methylester (62020-09-1) + 4-chloro-6-(trifluoromethyl)pyrimidine (37552-81-1) → methyl 2-methanesulfonyl-2-(6-(trifluoromethyl)pyrimidin-4-yl) acetate

Conditions	Yield
Stage #1: Methyl α-(methylsulfonyl)acetate With sodium hydride In N,N-dimethyl-formamide for 0.0833333h; Stage #2: 4-chloro-6-(trifluoromethyl)pyrimidine In N,N-dimethyl-formamide at 20℃;	36%

carbon dioxide (124-38-9) + 4-chloro-6-(trifluoromethyl)pyrimidine (37552-81-1) → 4-chloro-6-(trifluoromethyl)pyrimidine-5-carboxylic acid (887626-22-4)

Conditions	Yield
Stage #1: 4-chloro-6-(trifluoromethyl)pyrimidine With n-butyllithium In tetrahydrofuran; hexane at -75℃; for 0.75h; Stage #2: carbon dioxide In tetrahydrofuran; hexane at -78℃; Stage #3: With hydrogenchloride In water pH=2;	31%

(E)-3-methoxy-2-(2-hydroxyphenyl)-acrylic acid methyl ester (114077-42-8) + 4-chloro-6-(trifluoromethyl)pyrimidine (37552-81-1) → methyl (E)-3-methoxy-2-[2-[6-(trifluoromethyl)pyrimidin-4-yl]oxyphenyl]prop-2-enoate

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 48h;	27%

1,5-anhydro-2,3-dideoxy-3-{[(1R,3S)-3-{[(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-yl]carbonyl}-3-(2,2-difluoroethyl)cyclopentyl]amino}-4-O-methyl-D-erythro-pentitol hydrochloride + 4-chloro-6-(trifluoromethyl)pyrimidine (37552-81-1) → 1,5-anhydro-2,3-dideoxy-3-{[(1R,3S)-3-(2,2-difluoroethyl)-3-({(1S,4S)-5-[6-(trifluoromethyl)pyrimidin-4-yl]-2,5-diazabicyclo[2.2.1]hept-2-yl}carbonyl)cyclopentyl]amino}-4-O-methyl-D-erythro-pentitol (1228111-74-7)

Conditions	Yield
With caesium carbonate; tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane; dimethyl sulfoxide at 100℃; for 21.5h;	20%

3-Oxo-cyclopentanecarboxylic acid (98-78-2) + 4-chloro-6-(trifluoromethyl)pyrimidine (37552-81-1) → 3-(4-chloro-6-(trifluoromethyl)pyrimidin-2-yl)cyclopentanone

Conditions	Yield
With ammonium peroxydisulfate; silver nitrate In water; acetonitrile at 60℃; for 2h; Minisci Aromatic Substitution;	18%

C23H21SN5O2 + 4-chloro-6-(trifluoromethyl)pyrimidine (37552-81-1) → 2-[1-(6-trifluoromethyl-pyrimidin-4-yl)-piperidin-4-yl]thiazole-4-carboxylic acid (5-benzoyl-1H-benzoimidazol-2-yl)-amide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 80℃; for 3h;

4-chloro-6-(trifluoromethyl)pyrimidine (37552-81-1) → 4‐(trifluoromethyl)pyrimidine‐5‐carboxylic acid (220880-12-6)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: butyllithium / tetrahydrofuran; hexane / 0.75 h / -75 °C 1.2: tetrahydrofuran; hexane / -78 °C 1.3: 31 percent / aq.HCl / H2O / pH 2 2.1: 83 percent / hydrogen; triethylamine / palladium on charcoal / methanol / 2 h / 25 °C / 760 Torr View Scheme

4-amino-phenol (123-30-8) + 4-chloro-6-(trifluoromethyl)pyrimidine (37552-81-1) → 4-(6-trifluoromethyl-pyrimidin-4-yloxy)-phenylamine

Conditions	Yield
With sodium hydride In 1,4-dioxane at 60 - 65℃; for 0.666667h;

3-carboxaldehyde-2-chloro-4-trifluoromethylpyridine (174008-48-1) + 4-chloro-6-(trifluoromethyl)pyrimidine (37552-81-1) → 1-(2-chloro-4-trifluoromethylpyrid-3-yl)-1-(6-chloro-4-trifluoromethylpyrimidin-3-yl)methanol + 1-(2-chloro-4-trifluoromethylpyrid-3-yl)-1-(6-chloro-4-trifluoromethylpyrimidin-5-yl)methanol (174008-41-4)

Conditions	Yield
With n-butyllithium; ammonium chloride; diisopropylamine In tetrahydrofuran

potassium dihydrogenphosphate + formic acid ethyl ester (109-94-4) + 4-chloro-6-(trifluoromethyl)pyrimidine (37552-81-1) → 4-chloro-5-formyl-6-trifluoromethylpyrimidine

Conditions	Yield
With n-butyllithium; diisopropylamine In tetrahydrofuran

aqueous HOAc + 2-chloro-4-methoxypyrimidine-5-carbaldehyde (142451-96-5) + 4-chloro-6-(trifluoromethyl)pyrimidine (37552-81-1) → 1-(4-trifluoromethyl-6-chloropyrimidin-5-yl)-1-(2-chloro-4-methoxypyrimidin-5-yl)methanol

Conditions	Yield
With n-butyllithium; diisopropylamine; lithium diisopropyl amide In tetrahydrofuran

sodium cyanide (773837-37-9) + 4-chloro-6-(trifluoromethyl)pyrimidine (37552-81-1) → 6-(trifluoromethyl)pyrimidine-4-carbonitrile (1359996-77-2)

Conditions	Yield
1,4-diaza-bicyclo[2.2.2]octane In water; dimethyl sulfoxide at 20℃; for 0.333333h;

1-[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-5-yl]methanamine (1289106-56-4) + 4-chloro-6-(trifluoromethyl)pyrimidine (37552-81-1) → 6-(trifluoromethyl)-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine (1289105-74-3)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one at 150℃; for 1h; Microwave irradiation;

Upstream product

• 824-72-6 P,P-dichlorophenylphosphine oxide 
• 1546-78-7 4-trifluoromethyl-1,6-dihydropyrimidine-6-oxide 
• 1546-78-7 6-trifluoromethyl-4-hydroxypyrimidine 

Downstream Products

• 845616-55-9 4-piperazin-1-yl-6-(trifluoromethyl)pyrimidine 
• 939047-74-2 ethyl 6-chloro-4-(trifluoromethyl)picolinate 
• 953414-03-4 N-{4-[(3-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)oxy]phenyl}-N'-[6-(trifluoromethyl)pyrimidin-4-yl]urea 
• 1353101-38-8 methyl 6-(trifluoromethyl)pyrimidine-4-carboxylate 
• 1366406-45-2 N-cyclobutyl-N-{4-fluoro-3-[6-(trifluoromethyl)pyrimidine-4-yl]benzyl}-1-methyl-1H-imidazole-4-carboxamide 
• 1415757-75-3 (S)-tert-butyl 2-(2-fluoro-4-(1-(6-(trifluoromethyl)pyrimidin-4-yl)-1H-pyrazole-4-carboxamido)phenyl)morpholine-4-carboxylate 
• 1400997-86-5 (R)-tert-butyl 2-(4-(6-trifluoromethylpyrimidin-4-ylamino)phenyl)morpholine-4-carboxylate 
• 672-41-3 4-amino-6-(trifluoromethyl)pyrimidine 

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