1514-96-1

Basic information

• Product Name: 4-CHLORO-2-(TRIFLUOROMETHYL)PYRIMIDINE
• Synonyms: IFLAB-BB F2124-0818;4-CHLORO-2-(TRIFLUOROMETHYL)PYRIMIDINE;4-Chloro-2-(trifluoromethyl)-1,3-diazine
• CAS NO: 1514-96-1
• Molecular Formula: C₅H₂ClF₃N₂
• Molecular Weight: 182.53
• Mol File: 1514-96-1.mol
• Article Data: 8

Chemical Properties

• Boiling Point: 115.367 °C at 760 mmHg
• Flash Point: 23.574 °C
• Appearance: Yellow power
• Density: 1.504 g/cm³
• Vapor Pressure: 22.675mmHg at 25°C
• Refractive Index: 1.445
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• PKA: -3.28±0.20(Predicted)
• CAS DataBase Reference: 4-CHLORO-2-(TRIFLUOROMETHYL)PYRIMIDINE(CAS DataBase Reference)
• NIST Chemistry Reference: 4-CHLORO-2-(TRIFLUOROMETHYL)PYRIMIDINE(1514-96-1)
• EPA Substance Registry System: 4-CHLORO-2-(TRIFLUOROMETHYL)PYRIMIDINE(1514-96-1)

Safety Data

• HazardClass: IRRITANT
• Hazardous Substances Data: 1514-96-1(Hazardous Substances Data)

Usage

General Description

4-CHLORO-2-(TRIFLUOROMETHYL)PYRIMIDINE is a chemical compound with the formula C5H2ClF3N2. It is a pyrimidine derivative that contains a chloro group and a trifluoromethyl group. 4-CHLORO-2-(TRIFLUOROMETHYL)PYRIMIDINE is a versatile building block in organic synthesis and is commonly used in the pharmaceutical and agrochemical industries. It is known for its potent biological activity and is used in the development of various drugs and other bioactive compounds. Its unique structure and properties make it a valuable tool for researchers and chemists in the development of new and innovative products.

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

Synthetic route

2-trifluoromethyl-4-hydroxypyrimidine (1546-80-1) → 4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1)

Conditions	Yield
With trichlorophosphate at 100 - 105℃; for 3h;	87%
With N,N-dimethyl-aniline; trichlorophosphate for 2h; Heating / reflux;	71%
With N,N-dimethyl-formamide; trichlorophosphate at 120℃; for 2h;	56%

4-chloro-6-methoxy-2-trifluoromethylpyrimidine → 4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: palladium 10% on activated carbon; hydrogen; triethylamine / 15 h / 25 - 35 °C / 760.05 Torr 2: hydrogen bromide / 5 h / 60 - 70 °C 3: trichlorophosphate / 3 h / 100 - 105 °C View Scheme

2-trifluoromethyl-4,6-dihydroxypyrimidine (672-47-9) → 4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1)

Conditions	Yield
Multi-step reaction with 5 steps 1: trichlorophosphate; triethylamine / 4 h / 5 - 105 °C 2: methanol / 5 h / 0 - 35 °C 3: palladium 10% on activated carbon; hydrogen; triethylamine / 15 h / 25 - 35 °C / 760.05 Torr 4: hydrogen bromide / 5 h / 60 - 70 °C 5: trichlorophosphate / 3 h / 100 - 105 °C View Scheme

4,6-dichloro-2-(trifluoromethyl)pyrimidine (705-24-8) → 4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: methanol / 5 h / 0 - 35 °C 2: palladium 10% on activated carbon; hydrogen; triethylamine / 15 h / 25 - 35 °C / 760.05 Torr 3: hydrogen bromide / 5 h / 60 - 70 °C 4: trichlorophosphate / 3 h / 100 - 105 °C View Scheme

4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1) + Cyclopentamine (1003-03-8) → N-cyclopentyl-2-(trifluoromethyl)pyrimidin-4-amine (917895-57-9)

Conditions	Yield
In 1,4-dioxane at 0 - 20℃;	99%

tributyl(1-ethoxyvinyl)stannane (97674-02-7) + 4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1) → 4-(1-ethoxyvinyl)-2-(trifluoromethyl)pyrimidine

Conditions	Yield
Stage #1: tributyl(1-ethoxyvinyl)stannane; 4-chloro-2-(trifluoromethyl)pyrimidine With bis-triphenylphosphine-palladium(II) chloride In N,N-dimethyl-formamide at 85℃; for 18h; Inert atmosphere; Stage #2: With potassium fluoride In water; N,N-dimethyl-formamide at 20℃; for 0.166667h; Inert atmosphere;	93%

4-piperidone monohydrochloride monohydrate (40064-34-4) + sodium carbonate (497-19-8) + 4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1) → 1-[2-(Trifluoromethyl)-4-pyrimidinyl]-4-piperidone

Conditions	Yield
In dichloromethane	92%

4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1) + diethyl malonate (105-53-3) → ethyl 2-[2-(trifluoromethyl)pyrimidin-4-yl]acetate

Conditions	Yield
Stage #1: diethyl malonate With sodium hydride In N,N-dimethyl-formamide at -78℃; for 0.166667h; Stage #2: 4-chloro-2-(trifluoromethyl)pyrimidine In N,N-dimethyl-formamide at 80 - 120℃;	92%

(S)-4-ethylaminomethyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (1048351-33-2) + 4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1) → (S)-4-{[ethyl-(2-trifluoromethyl-pyrimidin-4-yl)-amino]-methyl}-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (1048351-35-4)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In isopropyl alcohol at 180℃; for 0.5h; Microwave irradiation;	90%

methanol (67-56-1) + carbon monoxide (201230-82-2) + 4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1) → methyl 2-(trifluoromethyl)pyrimidine-4-carboxylate (878745-51-8)

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine at 80℃; under 2585.81 Torr; for 16h;	88%
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine at 80℃; for 16h; Inert atmosphere;	88%
With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; triethylamine at 60℃; under 3102.97 Torr; for 16h;	62%
With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; triethylamine at 60℃; under 3102.97 Torr;
With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; triethylamine at 60℃; under 3102.97 Torr;

tert-butyl 4-[(2-{[6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzimidazol-2-yl]amino}pyridin-4-yl)methyl]piperazine-1-carboxylate + 4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1) → tert-butyl 4-{[2-({6-[2-(trifluoromethyl)pyrimidin-4-yl]-1H-benzimidazol-2-yl}amino)pyridin-4-yl]methyl}piperazine-1-carboxylate

Conditions	Yield
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate In 1,4-dioxane; water for 24h; Suzuki Coupling; Reflux;	83%

tributyl(1-ethoxyvinyl)stannane (97674-02-7) + 4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1) → 1-(2-(trifluoromethyl)pyrimidin-4-yl)ethanone (878760-55-5)

Conditions	Yield
Stage #1: tributyl(1-ethoxyvinyl)stannane; 4-chloro-2-(trifluoromethyl)pyrimidine With bis-triphenylphosphine-palladium(II) chloride In N,N-dimethyl-formamide at 85℃; Inert atmosphere; Sealed tube; Stage #2: With potassium fluoride In diethyl ether; N,N-dimethyl-formamide at 20℃; Stage #3: With hydrogenchloride In water; N,N-dimethyl-formamide; acetone at 60℃; for 2h;	82%

N-phenylpyrrolidine (4096-21-3) + 4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1) → C15H14F3N3

Conditions	Yield
With (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(2-phenylpyridine(-1H))-iridium(III) hexafluorophosphate; sodium acetate In N,N-dimethyl acetamide; water at 0℃; Irradiation;	72%

N-ethyl-N-[(4-piperidinyl)methyl]acetamide hydrochloride + 4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1) → N-ethyl-N-[[1-[2-(trifluoromethyl)-4-pyrimidinyl]-4-piperidinyl]methyl]-acetamide

Conditions	Yield
With sodium carbonate In dichloromethane; N,N-dimethyl-formamide	67%

(S)-tert-butyl (1-(2-cyano-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)-2,4-dimethylpentan-2-yl)carbamate + 4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1) → (S)-tert-butyl (1-(2-cyano-4-(2-(trifluoromethyl)pyrimidin-4-yl)phenoxy)-2,4-dimethylpentan-2-yl) carbamate

Conditions	Yield
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate In 1,4-dioxane; water at 80℃; for 12h; Inert atmosphere;	64%

4-amino-phenol (123-30-8) + 4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1) → 4-{[2-(trifluoromethyl)pyrimidin-4-yl]oxy}aniline (871240-11-8)

Conditions	Yield
Stage #1: 4-amino-phenol With potassium tert-butylate In ISOPROPYLAMIDE at 20℃; for 0.25h; Stage #2: 4-chloro-2-(trifluoromethyl)pyrimidine In N,N-dimethyl-formamide at 20℃; for 16h;	63%

tert-butyl 3-(4-aminophenoxy)azetidine-1-carboxylate (643087-88-1) + 4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1) → tert-butyl 3-(4-(2-(trifluoromethyl)pyrimidin-4-ylamino)phenoxy)azetidine-1-carboxylate

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene In diethylene glycol dimethyl ether at 100℃; Inert atmosphere;	58%

2-(3-fluoro-4-methoxyphenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (754226-34-1) + 4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1) → 4-(3-fluoro-4-methoxyphenyl)-2-(trifluoromethyl)pyrimidine

Conditions	Yield
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; potassium bromide In 1,4-dioxane at 80℃; for 1.3h; Inert atmosphere;	53%

3-(5-aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenol + 4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1) → 5-(4-cyclobutyl-2-fluoro-3-{[2-(trifluoromethyl)pyrimidin-4-yl]oxy}phenyl)pyrazin-2-amine

Conditions	Yield
With caesium carbonate In dimethyl sulfoxide at 80℃; for 1h; Microwave irradiation;	52%
With caesium carbonate In dimethyl sulfoxide at 80℃; for 1h; Inert atmosphere; Microwave irradiation;

(S)-tert-butyl (1-(2-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)-2,4-dimethylpentan-2-yl)carbamate + 4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1) → (S)-tert-butyl(1-(2-chloro-4-(2-(trifluoromethyl)pyrimidin-4-yl)phenoxy)-2,4-dimethylpentan-2-yl) carbamate

Conditions	Yield
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate In 1,4-dioxane; water at 80℃; for 12h; Inert atmosphere;	52%

(R)-N-(4-cyanophenylethyl)piperidine-3-carboxamide (1595144-12-9) + 4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1) → (R)-N-(4-cyanophenylethyl)-1-(2-(trifluoromethyl)pyrimidin-6-yl)piperidine-3-carboxamide (1595144-33-4)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In isopropyl alcohol at 100℃; for 2h; Sealed tube;	50%

4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1) + tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (336191-17-4) → tert-butyl 8-(2-(trifluoromethyl)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate (1246508-00-8)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In isopropyl alcohol at 75℃; for 0.75h; Microwave irradiation;	47%

(R)-4-fluoro-N-(1-(5,6,7,8-tetrahydro-1,5-naphthyridin-2-yl)ethyl)benzamide hydrochloride + 4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1) + trifluoroacetic acid (76-05-1) → C22H19F4N5O*C2HF3O2

Conditions

Yield

Stage #1: (R)-4-fluoro-N-(1-(5,6,7,8-tetrahydro-1,5-naphthyridin-2-yl)ethyl)benzamide hydrochloride; 4-chloro-2-(trifluoromethyl)pyrimidine With 2’-(bis(3,5-bis(trifluoromethyl)phenyl)phosphino)-3’,6’-dimethoxy-N2,N2,N6,N6-tetramethyl-[1,1‘-biphenyl]-2,6-diamine; C34H29F12N2O2P*Pd(2+)*C12H10N(1-)*CH3O3S(1-); sodium t-butanolate at 80℃; Inert atmosphere; Stage #2: trifluoroacetic acid In water; acetonitrile Inert atmosphere;

47%

(S)-tert-butyl (1-(4-bromo-2-methylphenoxy)-2,4-dimethylpentan-2-yl)carbamate + 4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1) → (S)-tert-butyl (2,4-dimethyl-1-(2-methyl-4-(2-(trifluoromethyl)pyrimidin-4-yl)phenoxy)pentan-2-yl)carbamate

Conditions	Yield
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium bromide In 1,4-dioxane at 80℃; for 1.3h; Inert atmosphere; Microwave irradiation;	44%

tert-butyl 3-(4-aminobenzylidene)azetidine-1-carboxylate + 4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1) → tert-butyl 3-[[4-[[2-(trifluoromethyl)pyrimidin-4-yl]amino]phenyl]methylene]azetidine-1-carboxylate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl acetamide at 100℃; for 1h; Inert atmosphere; Microwave irradiation;	38%

2-Aminopyrazine (5049-61-6) + 4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1) → C9H6F3N5

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 90℃; for 40h; Inert atmosphere;	37%

tert-butyl (11bR)-9-amino-1,3,4,6,7,11b-hexahydropyrazino[2,1-a]isoquinoline-2-carboxylate + 4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1) → tert-butyl (11bR)-9-[[2-(trifluoromethyl)pyrimidin-4-yl]amino]-1,3,4,6,7,11b-hexahydropyrazino[2,1-a]isoquinoline-2-carboxylate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl acetamide at 100℃;	27%

ethanol (64-17-5) + carbon monoxide (201230-82-2) + 4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1) → 2-trifluoromethylpyrimidine-4-carboxylic acid ethyl ester

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine at 60℃; under 2585.81 Torr; for 16h;	25%

C17H21N5O + 4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1) → 6,6-dimethyl-N-[trans-2-phenylcyclopropyl]-3-{[2-(trifluoromethyl)pyrimidin-4-yl]amino}-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxamide trifluoroacetate

Conditions	Yield
With triethylamine In isopropyl alcohol at 140℃; for 0.333333h; Microwave irradiation;	6.4%

3-amino-N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxamide (898044-54-7) + 4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1) → N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-{[2-(trifluoromethyl)pyrimidin-4-yl]amino}-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxamide trifluoroacetate

Conditions	Yield
With triethylamine In isopropyl alcohol at 140℃; for 0.333333h; Microwave irradiation;	4%

4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1) + malonic acid dimethyl ester (108-59-8) → dimethyl 2-trifluoromethyl-4-pyrimidylmalonate (119884-64-9)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide 1.) 2.) 60 deg C, 2 hrs.,;	0.3 g

8-fluoro-3-(tri-n-butylstannyl)-7-[2-(triethylsilyloxy)prop-2-yl]imidazo[1,2-a]pyridine (628323-04-6) + 4-chloro-2-(trifluoromethyl)pyrimidine (1514-96-1) → 2-[8-fluoro-3-(2-trifluoromethylpyrimidin-4-yl)imidazo[1,2-a]pyridin-7-yl]propan-2-ol

Conditions	Yield
Stage #1: 8-fluoro-3-(tri-n-butylstannyl)-7-[2-(triethylsilyloxy)prop-2-yl]imidazo[1,2-a]pyridine; 4-chloro-2-(trifluoromethyl)pyrimidine; tetrakis(triphenylphosphine) palladium(0) In tetrahydrofuran for 3h; Heating / reflux; Stage #2: With hydrogenchloride In ethanol; 2-Methylpentane; water; ethyl acetate

Upstream product

• 705-24-8 4,6-dichloro-2-(trifluoromethyl)pyrimidine 
• 672-47-9 2-trifluoromethyl-4,6-dihydroxypyrimidine 
• 1546-80-1 2-trifluoromethyl-4-hydroxypyrimidine 

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