37552-81-1

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

• 1353101-38-8 methyl 6-(trifluoromethyl)pyrimidine-4-carboxylate 
• 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 
• 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 
• 845616-55-9 4-piperazin-1-yl-6-(trifluoromethyl)pyrimidine 
• 672-41-3 4-amino-6-(trifluoromethyl)pyrimidine 

Relevant academic research and scientific papers

Synthesis and Antifungal and Insecticidal Activities of Novel N -Phenylbenzamide Derivatives Bearing a Trifluoromethylpyrimidine Moiety

Seventeen novel N-phenylbenzamide derivatives bearing a trifluoromethylpyrimidine moiety were synthesized via four-step reactions. Their antifungal and insecticidal properties were evaluated. Antifungal test results demonstrated that some of the synthesized compounds showed better in vitro bioactivities against Phomopsis sp., Botryosphaeria dothidea (B. dothidea), and Botrytis cinerea (B. cinerea) at 50 μg/mL than pyrimethanil. Unfortunately, the synthesized compounds revealed lower insecticidal activities against Spodoptera frugiperda (S. frugiperda) and Mythimna separata (M. separata) at 500 μg/mL than chlorantraniliprole.

Trifluoromethyl pyrimidine containing Ferulamide derivative and preparation and use thereof

The invention discloses a trifluoromethyl pyrimidine containing Ferulamide derivative. The trifluoromethyl pyrimidine containing Ferulamide derivative is characterized by having a structural general formula represented by (I) shown in the description, wherein R1 is H, methyl, ethyl, n-propyl, isopropyl, n-butyl, phenyl, methylmercapto, ethylmercapto, fluoro-, chloro-, bromo-, trifluoromethyl and N,N-dimethylamine, R2 is monosubstituted, disubstituted and trisubstituted, and R2 is H, methyl, ethyl, methoxy, ethoxy, fluoro-, chloro-, bromo-, iodo-, trifluoromethyl, nitro- and hydroxyl. The trifluoromethyl pyrimidine containing Ferulamide derivative can resist major pathogenic bacteria, i.e., Phomopsis Sp. and Botryosphaeria dothidea of kiwi fruit soft rot.

COMPOUNDS AS MODULATORS OF ROR GAMMA

The present invention encompasses compounds of the formula (I)(I) wherein the variables are defined herein which are suitable for the modulation of RORγ and the treatment of diseases related to the modulation of RORγ. The present invention also encompasses processes of making compounds of formula (I) and pharmaceutical preparations containing them.

Synthesis method of 6-trifluoromethyl-N-(2-trifluoromethylindole-5-yl)methyl-4-pyrimidinamine

The invention discloses a synthesis method of 6-trifluoromethyl-N-(2-trifluoromethylindole-5-yl)methyl-4-pyrimidinamine, relates to a chemical synthesis method, and especially relates to a novel synthesis method of 6-trifluoromethyl-N-(2-trifluoromethylindole-5-yl)methyl-4-pyrimidinamine. According to the synthesis method, 6-trifluoromethyl-N-(2-trifluoromethylindole-5-yl)methyl-4-pyrimidinamine is obtained through Claisen condensation, cyclization, chlorination, and hydrocarbonylation reactions. Compared with the conventional methods, the cyclization is improved, materials can be continuously fed in chlorination and hydrocarbonylation steps, one-pot operation is realized, and the method is suitable for industrial production.

AZAINDOLE COMPOUNDS AS MODULATORS OF RORC

The present invention encompasses compounds of the formula (I), wherein the variables are defined herein which are suitable for the modulation of RORC and the treatment of diseases related to the modulation of RORC. The present invention also encompasses processes of making compounds of formula (I) and pharmaceutical preparations containing them.

CYCLOPROPANECARBOXAMIDO-SUBSTITUTE AROMATIC COMPOUNDS AS ANTI-TUMOR AGENTS

Provided are cyclopropanecarboxamido-substituted aromatic compounds that inhibit protein kinases and their use in anti-tumor area. In particular, tyrosine-kinase inhibitors and Raf-kinase inhibitors as anti-tumor agents, their preparation, pharmaceutical composition, and their use in the treatment of cancer are also provided.

COMPOUNDS AS MODULATORS OF ROR GAMMA

The present invention encompasses compounds of the formula (I) wherein the variables are defined herein which are suitable for the modulation of RORγ and the treatment of diseases related to the modulation of RORγ. The present invention also encompasses processes of making compounds of formula (I) and pharmaceutical preparations containing them.

PYRIMIDINE COMPOUND AND ITS USE IN PEST CONTROL

A pyrimidine compound represented by below formula (I) has excellent control activity against pests and is useful as an active ingredient of a pest controlling agent.

QUINAZOLIN-4-ONE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

The invention relates to chemical compounds of the formula (I): or pharmaceutically acceptable salts thereof, which possess B-Raf inhibitory activity and are accordingly useful for their anti-cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments of use in the production of an anti-cancer effect in a warm-blooded animal such as man.

Metal-bearing and trifluoromethyl-substituted pyrimidines: Generation and functionalization

5-Pyrimidyllithium species are fairly stable when the metal is flanked by two electron-withdrawing substituents such as trifluoromethyl and chlorine or bromine. Thus, the corresponding 5-carboxylic acids are produced in high yields from 4,5-dibromo-6-(trifluoromethyl)pyrimidine and 5-bromo-4-chloro-6- (trifluoromethyl)pyrimidine upon halogen/metal permutation accomplished with isopropylmagnesium chloride or butyllithium followed by carboxylation. Satisfactory or excellent yields of 5-carboxylic acids are equally obtained when 4-chloro-, 2,4-dichloro- and 2,4-dibromo-6-(trifluoromethyl)pyrimidine are deprotonated with lithium diisopropylamide before being allowed to react with dry ice. In contrast, consecutive treatment of 2-bromo-4-(trifluoromethyl) pyrimidine and 2-chloro-5-iodo-4-(trifluoromethyl)pyrimidine with butyllithium affords the expected carboxylic acids in only poor yields and not even trace amounts of acid were detected when 4-bromo-6-(trifluoromethyl)pyrimidine served as the substrate. The formation of bipyrimidines, emerging from either one of two competing mechanistic pathways, is a permanently menacing side reaction. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.