252742-72-6

Basic information

• Product Name: 5-CHLOROMETHYL-2,4-DIHYDRO-[1,2,4]TRIAZOL-3-ONE
• Synonyms: 5-CHLOROMETHYL-2,4-DIHYDRO-[1,2,4]TRIAZOL-3-ONE;5-(CHLOORMETHYL)-1,2-DIHYDRO-3H-1,2,4-TRIAZOOL-3-ON;3-Chloromethyl-1,2,4-triazol-5-one;3-Chloromethyl-1,2,4-triazolin-5-one;3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one;3-(chloroMethyl)-4,5-dihydro-1H-1,2,4-triazol-5-one;5-ChloroMethyl-2H-1,2,4-triazolin-3-one;3-Chloromethyl-1,2,4-triazolin-5-one 5-Chloromethyl-2,4-dihydro-[1,2,4]triazol-3-one
• CAS NO: 252742-72-6
• Molecular Formula: C₃H₄ClN₃O
• Molecular Weight: 133.54
• EINECS: 1533716-785-6
• Product Categories: pharmacetical
• Mol File: 252742-72-6.mol
• Article Data: 12

Chemical Properties

• Melting Point: 199°C(lit.)
• Boiling Point: 426 °C at 760 mmHg
• Flash Point: 211.5 °C
• Appearance: /
• Density: 1.837 g/cm³
• Vapor Pressure: 7.35E-08mmHg at 25°C
• Refractive Index: 1.711
• Storage Temp.: Keep in dark place,Sealed in dry,Room Temperature
• Solubility: soluble in Methanol
• PKA: 7.46±0.20(Predicted)
• CAS DataBase Reference: 5-CHLOROMETHYL-2,4-DIHYDRO-[1,2,4]TRIAZOL-3-ONE(CAS DataBase Reference)
• NIST Chemistry Reference: 5-CHLOROMETHYL-2,4-DIHYDRO-[1,2,4]TRIAZOL-3-ONE(252742-72-6)
• EPA Substance Registry System: 5-CHLOROMETHYL-2,4-DIHYDRO-[1,2,4]TRIAZOL-3-ONE(252742-72-6)

Safety Data

• RIDADR: UN 3261 8/PG II
• HazardClass: 8
• PackingGroup: II
• Hazardous Substances Data: 252742-72-6(Hazardous Substances Data)

Usage

General Description

5-Chloromethyl-2,4-dihydro-[1,2,4]triazol-3-one, also known as CDMT, is a chemical compound. 5-CHLOROMETHYL-2,4-DIHYDRO-[1,2,4]TRIAZOL-3-ONE is notable for being a triazolone derivative. Triazolones are a class of heterocyclic chemical compounds that contain a five-membered ring with three nitrogen atoms and two carbon atoms. The specific structural features of CDMT include a triazol-3-one ring and a chloromethyl group. As a derivative of triazolone, 5-chloromethyl-2,4-dihydro-[1,2,4]triazol-3-one may have potential uses in various chemical and pharmaceutical applications. However, detailed information about its physical properties, safety, handling, and specific uses may not be readily available, implying it's likely an experimental or less extensively studied compound.

InChI:InChI=1/C3H4ClN3O/c4-1-2-5-3(8)7-6-2/h1H2,(H2,5,6,7,8)

Synthetic route

semicarbazide hydrochloride (563-41-7) + 2-chloro-1,1,1-trimethoxyethane (74974-54-2) → 3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one (252742-72-6)

Conditions	Yield
In methanol at 20℃; for 72h;	98%
In methanol at 20℃;	62%
In methanol at 20℃; for 72h;
In methanol at 20℃; for 144h;
In methanol at 20℃; for 3h;

5-hydroxymethyl-2,4-dihydro[1,2,4]triazol-3-one (24021-90-7) → 3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one (252742-72-6)

Conditions	Yield
With thionyl chloride In acetonitrile at 5 - 20℃;	90.7%
With thionyl chloride In acetonitrile at 20℃; for 18h;	87%
With thionyl chloride In hexane; acetonitrile	87.4%
With thionyl chloride at 20℃; for 18h; Inert atmosphere;

N4-semicarbazide hydrochloride + ethyl chloroacetimidate hydrochloride (36743-66-5) → 3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one (252742-72-6)

Conditions	Yield
In ethanol at 20℃; for 35h;	62%

N4-semicarbazide hydrochloride + methyl 2-chloroacetimidate hydrochloride (70737-12-1) → 3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one (252742-72-6)

Conditions	Yield
In methanol for 70h;	60%

2-chloro-1,1,1-trimethoxyethane (74974-54-2) → 3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one (252742-72-6)

Conditions	Yield
In methanol; toluene

hydrazine carboxamide (4426-72-6, 51433-48-8) + 2-chloro-1,1,1-trimethoxyethane (74974-54-2) → 3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one (252742-72-6)

3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one (252742-72-6) → 3-(aminomethyl)-1,4-dihydro-1,2,4-triazol-5-one (83160-78-5)

Conditions	Yield
With ammonia In methanol at 20℃;	100%
With ammonia In methanol at 20℃;

(2S,3S)-2-[(1S)-1-(3,5-bis-trifluoro-methylphenyl)ethoxy]-3-(4-fluorophenyl)morpholine (1242175-38-7) + 3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one (252742-72-6) → C23H21F7N4O3 (1242175-40-1)

Conditions	Yield
With potassium carbonate In water; N,N-dimethyl-formamide at 0℃;	99.2%

3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one (252742-72-6) + (2R,3S)-2-((R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(4-fluorophenyl)morpholine 4-methylbenzenesulfonate → aprepitant (170729-80-3)

Conditions	Yield
With potassium carbonate In water; N,N-dimethyl-formamide at 0℃; for 3h;	99%

3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one (252742-72-6) + (2R,3R)-2-[(1R)-1-(3,5-bis-trifluoro-methylphenyl)ethoxy]-3-(4-fluorophenyl)morpholine (380499-06-9) → C23H21F7N4O3 (1148113-53-4)

Conditions	Yield
With potassium carbonate In water; N,N-dimethyl-formamide at 0℃;	99%

2-[1-(3,5-bis-trifluoro-methylphenyl)ethoxy]-3-(4-fluorophenyl)morpholine (1242175-36-5) + 3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one (252742-72-6) → C23H21F7N4O3 (1242175-34-3)

Conditions	Yield
With potassium carbonate In water; N,N-dimethyl-formamide at 0℃;	98.6%

2-[1-(3,5-bis-trifluoro-methylphenyl)ethoxy]-3-(4-fluorophenyl)morpholine (170902-80-4) + 3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one (252742-72-6) → C23H21F7N4O3 (172822-28-5)

Conditions	Yield
With potassium carbonate In water; N,N-dimethyl-formamide at 0℃;	98.6%

(2S,3R)-2-[(1R)-1-(3,5-bis-trifluoro-methylphenyl)ethoxy]-3-(4-fluorophenyl)morpholine (1185503-48-3) + 3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one (252742-72-6) → C23H21F7N4O3 (1185502-97-9)

Conditions	Yield
With potassium carbonate In water; N,N-dimethyl-formamide at 0℃;	98.2%
With potassium carbonate In N,N-dimethyl-formamide at 20℃;

(2S,3R)-2-[(1S)-1-(3,5-bis-trifluoro-methylphenyl)ethoxy]-3-(4-fluorophenyl)morpholine (327623-37-0) + 3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one (252742-72-6) → 5-[{(2S,3R)-2-((1S)-1-3,5-bis(trifluoro-methyl)phenylethoxy)-3-(4-fluorophenyl)-4-morpholinyl}methyl]-1,2-dihydro-3H-1,2,4-triazol-3-one (172822-29-6)

Conditions	Yield
With potassium carbonate In water; N,N-dimethyl-formamide at 0℃;	98%
With potassium carbonate In N,N-dimethyl-formamide at 20℃;

(2R,3R)-2-[(1S)-1-(3,5-bis-trifluoro-methylphenyl)ethoxy]-3-(4-fluorophenyl)morpholine (170729-79-0) + 3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one (252742-72-6) → C23H21F7N4O3 (170902-81-5)

Conditions	Yield
With potassium carbonate In water; N,N-dimethyl-formamide at 0℃;	98%

3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one (252742-72-6) + [2R-[2α(R*),3α]]-2-[1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholine hydrochloride → aprepitant (170729-80-3)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 0 - 10℃; for 4h;	92%

dibenzyl phosphochloridate (538-37-4) + 3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one (252742-72-6) → C17H17ClN3O4P

Conditions	Yield
With sodium hexamethyldisilazane In tetrahydrofuran at -5℃; Reagent/catalyst;	91%

C14H13F6NO3 + 3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one (252742-72-6) → C17H16F6N4O4

Conditions	Yield
With sodium hydroxide In acetonitrile at 30 - 40℃; for 2.5h;	89%

O-Trimethylsilylhydroxylamine (22737-36-6) + 4-bromobenzyl mercaptan (19552-10-4) + 3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one (252742-72-6) → 5-({[(4-bromophenyl)methyl]thio}methyl)-2,4-dihydro-3H-1,2,4-triazol-3-one (935760-75-1)

Conditions	Yield
With potassium carbonate In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 12h;	88%

4-bromobenzyl mercaptan (19552-10-4) + 3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one (252742-72-6) → 5-({[(4-bromophenyl)methyl]thio}methyl)-2,4-dihydro-3H-1,2,4-triazol-3-one (935760-75-1)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 12h;	88%

dibenzyl [[bis(benzyloxy)phosphoryl]oxy]phosphonate (990-91-0) + 3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one (252742-72-6) → C17H17ClN3O4P

Conditions	Yield
With potassium tert-butylate In tetrahydrofuran at -5℃;	86%

3-chloro-5-((2-oxo-4-(trifluoromethyl)-1,2-dihydropyridin-3-yl)oxy)benzonitrile (1155846-86-8) + 3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one (252742-72-6) → 3-chloro-5-((2-oxo-1-((5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl)-4-(trifluoromethyl)-1,2-dihydropyridin-3-yl)oxy)benzonitrile (1338226-05-3)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at -10 - 10℃; for 9h; Large scale;	81%

Benzyl-{3-[(R)-1-(3,5-bis-trifluoromethyl-phenyl)-ethoxymethyl]-3-phenyl-cyclobutyl}-amine (606929-58-2) + 3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one (252742-72-6) → 5-[(Benzyl-{3-[(R)-1-(3,5-bis-trifluoromethyl-phenyl)-ethoxymethyl]-3-phenyl-cyclobutyl}-amino)-methyl]-2,4-dihydro-[1,2,4]triazol-3-one (606929-61-7)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 0℃; for 9h;	77%

3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one (252742-72-6) + [2R-[2α(R*),3α]]-2-[1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholine (171338-27-5) → aprepitant (170729-80-3)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 0.5h;	68%

phenylmethanethiol (100-53-8) + 3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one (252742-72-6) → 5-[(benzylthio)methyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (866602-60-0)

Conditions	Yield
With potassium carbonate In DMF (N,N-dimethyl-formamide) at 20℃; for 20.5h;	61%

N-(2,4-dichlorobenzyl)-7-[(3RS,5SR)-3,5-dimethylpiperazin-1-yl]-6-fluoro-8-methoxy-4-oxo-1-(2,2,2-trifluoroethyl)-1,4-dihydroquinoline-3-carboxamide (874481-18-2) + 3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one (252742-72-6) → N-(2,4-dichlorobenzyl)-7-{(3RS,5SR)-3,5-dimethyl-4-[(5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl]piperazin-1-yl}-6-fluoro-8-methoxy-4-oxo-1-(2,2,2-trifluoroethyl)-1,4-dihydroquinoline-3-carboxamide

Conditions	Yield
With potassium carbonate; potassium iodide In acetonitrile at 50℃;	40%

3,4-dihydro-2H-pyrido[3,2-b ][1,4]oxazine (20348-23-6) + 3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one (252742-72-6) → C10H11N5O2

Conditions	Yield
Stage #1: 3,4-dihydro-2H-pyrido[3,2-b ][1,4]oxazine With potassium hexamethylsilazane In N,N-dimethyl-formamide; toluene at 0℃; for 0.333333h; Stage #2: 3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one In N,N-dimethyl-formamide; toluene at 20℃; for 2h;	36%

cis-4-[[3,5-bis(trifluoromethyl)benzyl]oxy]-3-phenylpiperidine hydrochloride + 3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one (252742-72-6) → 5-[[cis-4-[[3,5-bis(trifluoromethyl)benzyl]oxy]-3-phenylpiperidinyl]methyl]-2,4-dihydro-3H-1,2,4-triazol-3-one

Conditions	Yield
With potassium carbonate In DMF (N,N-dimethyl-formamide); water at 0℃; for 3h;	29%

4-(2-fluorophenoxymethyl)piperidine hydrochloride (614731-22-5) + 3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one (252742-72-6) → 5-(4-(2-Fluorophenoxymethyl)piperidino]methyl-2,4-dihydro-[1,2,4]triazol-3-one (614729-03-2)

Conditions	Yield
With potassium carbonate In water; ethyl acetate; acetonitrile	21%

2-(2-Fluorophenyl)-1-(piperidin-4-yl)ethanone hydrochloride (614729-48-5) + 3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one (252742-72-6) → 5-[4-(2-(2-Fluorophenyl)acetyl]piperidino]methyl-2,4-dihydro-[1,2,4]triazol-3-one (614729-09-8)

Conditions	Yield
With potassium carbonate In diethyl ether; water; ethyl acetate; acetonitrile	7%

3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one (252742-72-6) + [2R-[2α(R*),3α]]-2-[1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholine (171338-27-5) → 5-[[(2R,3S)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)-4-morpholinyl]methyl]-1,2-dihydro-3H-1,2,4-triazol-3-one (172822-29-6)

Conditions	Yield
With potassium carbonate In water; N,N-dimethyl-formamide at 0℃; for 4h;

benzyl[(2S,3S)-2-phenyl-3-piperidinyl]carbamate + 3-(chloromethyl)-1H-1,2,4-triazol-5(4H)-one (252742-72-6) → benzyl[(2S,3S)-1-[(5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl]-2-phenyl-3-piperidinyl]carbamate

Conditions	Yield
With potassium carbonate In DMF (N,N-dimethyl-formamide) at 20℃; for 1h;

Upstream product

• 36743-66-5 ethyl chloroacetimidate hydrochloride 
• 70737-12-1 methyl 2-chloroacetimidate hydrochloride 
• 4426-72-6 hydrazine carboxamide 
• 74974-54-2 2-chloro-1,1,1-trimethoxyethane 
• 24021-90-7 5-hydroxymethyl-2,4-dihydro[1,2,4]triazol-3-one 
• 563-41-7 semicarbazide hydrochloride 

Downstream Products

• 170729-80-3 aprepitant 
• 935760-75-1 5-({[(4-bromophenyl)methyl]thio}methyl)-2,4-dihydro-3H-1,2,4-triazol-3-one 
• 1338226-05-3 3-chloro-5-((2-oxo-1-((5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl)-4-(trifluoromethyl)-1,2-dihydropyridin-3-yl)oxy)benzonitrile 
• 83160-78-5 3-(aminomethyl)-1,4-dihydro-1,2,4-triazol-5-one 
• 1148113-53-4 C₂₃H₂₁F₇N₄O₃ 
• 172822-28-5 C₂₃H₂₁F₇N₄O₃ 
• 1242175-34-3 C₂₃H₂₁F₇N₄O₃ 
• 1242175-40-1 C₂₃H₂₁F₇N₄O₃ 
• 1185502-97-9 C₂₃H₂₁F₇N₄O₃ 
• 170902-81-5 C₂₃H₂₁F₇N₄O₃ 
• 172822-29-6 5-[{(2S,3R)-2-((1S)-1-3,5-bis(trifluoro-methyl)phenylethoxy)-3-(4-fluorophenyl)-4-morpholinyl}methyl]-1,2-dihydro-3H-1,2,4-triazol-3-one 
• 614729-03-2 5-(4-(2-Fluorophenoxymethyl)piperidino]methyl-2,4-dihydro-[1,2,4]triazol-3-one 
• 614729-09-8 5-[4-(2-(2-Fluorophenyl)acetyl]piperidino]methyl-2,4-dihydro-[1,2,4]triazol-3-one 

Relevant articles and documents

Synthetic method of 3-chloromethyl-1,2,4-triazolin-5-one

The invention relates to a synthetic method of 3-chloromethyl-1,2,4-triazolin-5-one. The 3-chloromethyl-1,2,4-triazolin-5-one is prepared by mixing chloroacetonitrile, an alcohol and a solvent A. Compared with a conventional process, the synthesis method has the advantages that the raw materials with low price are selected, and production cost is remarkably reduced. For the whole technological process, the synthetic route is shortened, and production efficiency is improved. Production operation and quality control are more convenient while the production process is simplified.

NOVEL COMPOUNDS AS INDOLEAMINE 2,3-DIOXYGENASE INHIBITORS

Disclosed herein are compounds of formula (I) which are inhibitors of an IDO enzyme:(I). Also disclosed herein are uses of the compounds in the potential treatment or prevention of an IDO-associated disease or disorder. Also disclosed herein are compositions comprising these compounds. Further disclosed herein are uses of the compositions in the potential treatment or prevention of an IDO-associated disease or disorder.

SUBSTITUTED NAPHTHYRIDINES AND THEIR USE AS MEDICAMENTS

The invention relates to new substituted naphthyridines of formula 1, as well as pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof, wherein R1 is selected from among —O—R3 or —NR3R4,R3 is C1-6-alkyl which is substituted by R5 and R6,R5 is selected from hydrogen, branched or linear C1-6-alkyl, C2-6-alkenyl, —C1-6-alkylen-O—C1-3-alkyl, C1-3-haloalkyl,R6 is ring X wherein n is either 0 or 1, and is a either a single or a double bond andwherein A, B, D and E are each independently from one another selected from CH2, CH, C, N, NH, O or S and wherein ring X is attached to the molecule either via position A, B, D or E, wherein said ring X may optionally be further substituted by one, two or three residues each selected individually from the group consisting of -oxo, hydroxy, —C1-3-alkyl, —C1-3-haloalkyl, —O—C1-3-alkyl, —C1-3-alkanol and halogen,and wherein R4, R2, R7, R8, R9, R10, R11 and Q may have the meanings as given in claim 1, as well as pharmaceutical compositions containing these compounds.