6021-21-2

Basic information

• Product Name: N-(2-benzoyl-4-chlorophenyl)-2-chloro-N-methylacetamide
• Synonyms: 2-chloro-N-[4-chloro-2-(oxo-phenylmethyl)phenyl]-N-methylacetamide;N-(2-benzoyl-4-chlorophenyl)-2-chloro-N-methylacetamide;Einecs 227-875-3;5-Chloro-2-(2-chloro-N-methylacetamido)benzophenone;N-Methyl-2'-benzoyl-2,4'-dichloroacetanilide;2-N-MethylchloroacetilaMido-5-chlorobenzophenone;DiazepaM IMpurity B;2-chloro-N-(4-chloro-2-phenylcarbonyl-phenyl)-N-methyl-ethanamide
• CAS NO: 6021-21-2
• Molecular Formula: C₁₆H₁₃Cl₂NO₂
• Molecular Weight: 322.18592
• EINECS: 227-875-3
• Mol File: 6021-21-2.mol
• Article Data: 5

Chemical Properties

• Melting Point: 122-124℃
• Boiling Point: 509.3 °C at 760 mmHg
• Flash Point: 261.8 °C
• Appearance: /
• Density: 1.328
• Vapor Pressure: 1.72E-10mmHg at 25°C
• Refractive Index: 1.616
• Storage Temp.: -20°C Freezer, Under inert atmosphere
• Solubility: Chloroform (Slightly), DMSO (Slightly), Ethanol (Slightly, Sonicated), Methanol
• PKA: -2.06±0.50(Predicted)
• CAS DataBase Reference: N-(2-benzoyl-4-chlorophenyl)-2-chloro-N-methylacetamide(CAS DataBase Reference)
• NIST Chemistry Reference: N-(2-benzoyl-4-chlorophenyl)-2-chloro-N-methylacetamide(6021-21-2)
• EPA Substance Registry System: N-(2-benzoyl-4-chlorophenyl)-2-chloro-N-methylacetamide(6021-21-2)

Safety Data

• Hazardous Substances Data: 6021-21-2(Hazardous Substances Data)

Usage

Uses

N-(2-Benzoyl-4-chlorophenyl)-2-chloro-N-methylacetamide (Diazepam EP Impurity B) is the impurity of Temazepam (T017200), which is a pharmacologically active metabolite of Diazepam. It is used as a sedative and hypnotic drug.

InChI:InChI=1/C16H13Cl2NO2/c1-19(15(20)10-17)14-8-7-12(18)9-13(14)16(21)11-5-3-2-4-6-11/h2-9H,10H2,1H3

Synthetic route

chloroacetyl chloride (79-04-9) + 5-chloro-2-(methylamino)benzophenone (1022-13-5) → 2-(2-chloro-N-methyl-acetamido)-5-chlorobenzophenone (6021-21-2)

Conditions	Yield
In 2-methyltetrahydrofuran; dichloromethane at 90℃; under 5171.62 Torr; Temperature; Flow reactor;	99%
at 25℃; for 5h; Inert atmosphere;	94.5%
With sodium hydrogencarbonate In toluene at 40℃; for 2h;	92%
In toluene Solvent;
In acetonitrile Mechanism; Solvent;

2-(2-chloro-N-methyl-acetamido)-5-chlorobenzophenone (6021-21-2) → diazepam (439-14-5)

Conditions	Yield
With hexamethylenetetramine; ammonia; nitric acid In methanol; water; toluene	96.09%
With hexamethylenetetramine; urotropin hydrochloride In ethanol Heating;	90%
With hexamethylenetetramine; ammonia In methanol at 60℃; for 6h;	58.4%

pyridine (110-86-1) + 2-(2-chloro-N-methyl-acetamido)-5-chlorobenzophenone (6021-21-2) → 1-(6-Chloro-1-methyl-2-oxo-4-phenyl-1,2-dihydro-quinolin-3-yl)-pyridinium; chloride (80356-39-4)

Conditions	Yield
	94%

2-(2-chloro-N-methyl-acetamido)-5-chlorobenzophenone (6021-21-2) → 6-chloro-3,4-epoxy-1,2,3,4-tetrahydro-1-methyl-2-oxo-4-phenylquinoline (37393-81-0) + 6-chloro-1,2-dihydro-3-hydroxy-1-methyl-2-oxo-4-phenylquinoline (37393-79-6) + 3-amino-6-chloro-1,2-dihydro-1-methyl-2-oxo-4-phenylquinoline (5220-02-0) + 3,6-dichloro-1,2-dihydro-1-methyl-2-oxo-4-phenylquinoline + 6-Chloro-3-methyl-7b-phenyl-1,1a,3,7b-tetrahydro-1,3-diaza-cyclopropa[a]naphthalen-2-one + diazepam (439-14-5)

Conditions	Yield
With ammonia In ethanol at 80℃; for 2h; Mechanism; further reagent;	A n/a B n/a C n/a D n/a E n/a F 65%

2-(2-chloro-N-methyl-acetamido)-5-chlorobenzophenone (6021-21-2) → 6-chloro-1,2-dihydro-3-hydroxy-1-methyl-2-oxo-4-phenylquinoline (37393-79-6) + 3-amino-6-chloro-1,2-dihydro-1-methyl-2-oxo-4-phenylquinoline (5220-02-0) + 3,6-dichloro-1,2-dihydro-1-methyl-2-oxo-4-phenylquinoline + diazepam (439-14-5)

Conditions	Yield
With ammonia In ethanol at 80℃; for 2h; Further byproducts given;	A n/a B n/a C n/a D 65%

2-(2-chloro-N-methyl-acetamido)-5-chlorobenzophenone (6021-21-2) → 6-chloro-3,4-epoxy-1,2,3,4-tetrahydro-1-methyl-2-oxo-4-phenylquinoline (37393-81-0) + 3,6-dichloro-1,2-dihydro-1-methyl-2-oxo-4-phenylquinoline

Conditions	Yield
With sodium hydrogencarbonate In ethanol at 60℃; for 48h;	A n/a B 5.3%

3-ethylamino propionitrile (21539-47-9) + 2-(2-chloro-N-methyl-acetamido)-5-chlorobenzophenone (6021-21-2) → N-(2-Benzoyl-4-chloro-phenyl)-2-[(2-cyano-ethyl)-ethyl-amino]-N-methyl-acetamide

Conditions	Yield
In 1,4-dioxane

3-(butylamino)propanenitrile (693-51-6) + 2-(2-chloro-N-methyl-acetamido)-5-chlorobenzophenone (6021-21-2) → N-(2-Benzoyl-4-chloro-phenyl)-2-[butyl-(2-cyano-ethyl)-amino]-N-methyl-acetamide (59049-46-6)

Conditions	Yield
In 1,4-dioxane

N-sec-butyl-β-alanine nitrile (21539-52-6) + 2-(2-chloro-N-methyl-acetamido)-5-chlorobenzophenone (6021-21-2) → N-(2-Benzoyl-4-chloro-phenyl)-2-[sec-butyl-(2-cyano-ethyl)-amino]-N-methyl-acetamide

Conditions	Yield
In 1,4-dioxane

2-aminoacetonitrile (540-61-4) + 2-(2-chloro-N-methyl-acetamido)-5-chlorobenzophenone (6021-21-2) → N-(2-Benzoyl-4-chloro-phenyl)-2-(cyanomethyl-amino)-N-methyl-acetamide (59049-39-7)

Conditions	Yield
In 1,4-dioxane

2-cyanoethylamine (151-18-8) + 2-(2-chloro-N-methyl-acetamido)-5-chlorobenzophenone (6021-21-2) → N-(2-Benzoyl-4-chloro-phenyl)-2-(2-cyano-ethylamino)-N-methyl-acetamide

Conditions	Yield
In 1,4-dioxane

N-(2-cyanoethyl)-N-methylamine (693-05-0) + 2-(2-chloro-N-methyl-acetamido)-5-chlorobenzophenone (6021-21-2) → N-(2-Benzoyl-4-chloro-phenyl)-2-[(2-cyano-ethyl)-methyl-amino]-N-methyl-acetamide (59049-40-0)

Conditions	Yield
In 1,4-dioxane

3-[(prop-2-en-1-yl)amino]propanenitrile (34508-81-1) + 2-(2-chloro-N-methyl-acetamido)-5-chlorobenzophenone (6021-21-2) → 2-[Allyl-(2-cyano-ethyl)-amino]-N-(2-benzoyl-4-chloro-phenyl)-N-methyl-acetamide

Conditions	Yield
In 1,4-dioxane

3-(pentylamino)propanenitrile (59676-91-4) + 2-(2-chloro-N-methyl-acetamido)-5-chlorobenzophenone (6021-21-2) → N-(2-Benzoyl-4-chloro-phenyl)-2-[(2-cyano-ethyl)-pentyl-amino]-N-methyl-acetamide

Conditions	Yield
In 1,4-dioxane

(+-)-3-amino-butyronitrile (16750-40-6) + 2-(2-chloro-N-methyl-acetamido)-5-chlorobenzophenone (6021-21-2) → N-(2-Benzoyl-4-chloro-phenyl)-2-(2-cyano-1-methyl-ethylamino)-N-methyl-acetamide

Conditions	Yield
In 1,4-dioxane

(RS)-2-methyl-3-aminopropionitrile (96-16-2) + 2-(2-chloro-N-methyl-acetamido)-5-chlorobenzophenone (6021-21-2) → N-(2-Benzoyl-4-chloro-phenyl)-2-(2-cyano-2-methyl-ethylamino)-N-methyl-acetamide

Conditions	Yield
In 1,4-dioxane

3-(methylamino)butanenitrile (67744-69-8) + 2-(2-chloro-N-methyl-acetamido)-5-chlorobenzophenone (6021-21-2) → N-(2-Benzoyl-4-chloro-phenyl)-2-[(2-cyano-1-methyl-ethyl)-methyl-amino]-N-methyl-acetamide (59049-42-2)

Conditions	Yield
In 1,4-dioxane

4-methylamino-butyronitrile (31058-09-0) + 2-(2-chloro-N-methyl-acetamido)-5-chlorobenzophenone (6021-21-2) → N-(2-Benzoyl-4-chloro-phenyl)-2-[(3-cyano-propyl)-methyl-amino]-N-methyl-acetamide

Conditions	Yield
In 1,4-dioxane

5-Aminopentanenitrile (6066-83-7) + 2-(2-chloro-N-methyl-acetamido)-5-chlorobenzophenone (6021-21-2) → N-(2-Benzoyl-4-chloro-phenyl)-2-[(3-cyano-propyl)-methyl-amino]-N-methyl-acetamide

3-butylamino-butyronitrile (54718-24-0) + 2-(2-chloro-N-methyl-acetamido)-5-chlorobenzophenone (6021-21-2) → N-(2-Benzoyl-4-chloro-phenyl)-2-[butyl-(2-cyano-1-methyl-ethyl)-amino]-N-methyl-acetamide

Conditions	Yield
In 1,4-dioxane

2-(Butylamino)-1-methylethyl Cyanide (63145-02-8) + 2-(2-chloro-N-methyl-acetamido)-5-chlorobenzophenone (6021-21-2) → N-(2-Benzoyl-4-chloro-phenyl)-2-[butyl-(2-cyano-2-methyl-ethyl)-amino]-N-methyl-acetamide

Conditions	Yield
In 1,4-dioxane

(R)-2-Methyl-3-methylamino-propionitrile (50840-30-7) + 2-(2-chloro-N-methyl-acetamido)-5-chlorobenzophenone (6021-21-2) → N-(2-Benzoyl-4-chloro-phenyl)-2-[(2-cyano-2-methyl-ethyl)-methyl-amino]-N-methyl-acetamide (50840-32-9)

Conditions	Yield
In 1,4-dioxane

glycine ethyl ester hydrochloride (5680-79-5) + 2-(2-chloro-N-methyl-acetamido)-5-chlorobenzophenone (6021-21-2) → ({[(2-Benzoyl-4-chloro-phenyl)-methyl-carbamoyl]-methyl}-amino)-acetic acid methyl ester (59049-68-2)

Conditions	Yield
With triethylamine In toluene

3-Allylamino-butyronitrile (76201-87-1) + 2-(2-chloro-N-methyl-acetamido)-5-chlorobenzophenone (6021-21-2) → 2-[Allyl-(2-cyano-1-methyl-ethyl)-amino]-N-(2-benzoyl-4-chloro-phenyl)-N-methyl-acetamide

Conditions	Yield
In 1,4-dioxane

2-(2-chloro-N-methyl-acetamido)-5-chlorobenzophenone (6021-21-2) → 3-amino-6-chloro-1,2,3,4-tetrahydro-4-hydroxy-1-methyl-2-oxo-4-phenylquinoline

Conditions	Yield
Multi-step reaction with 2 steps 1: NaHCO3 / ethanol / 48 h / 60 °C 2: NH3 / ethanol / 1 h / Heating View Scheme

2-(2-chloro-N-methyl-acetamido)-5-chlorobenzophenone (6021-21-2) → 3-pyridinio-6-chloro-1-methyl-4-phenyl-2-(1H)quinolone pseudo base chloride

Conditions	Yield
Multi-step reaction with 2 steps 1: 94 percent 2: 40percent sodium hydroxide / H2O View Scheme

2-(2-chloro-N-methyl-acetamido)-5-chlorobenzophenone (6021-21-2) → 3-amino-6-chloro-1,2-dihydro-1-methyl-2-oxo-4-phenylquinoline (5220-02-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 94 percent 2: 40percent sodium hydroxide / H2O 3: 38 percent / 220 °C / 0.5 Torr View Scheme

ethanolamine (141-43-5) + 2-(2-chloro-N-methyl-acetamido)-5-chlorobenzophenone (6021-21-2) → 10-chloro-7-methyl-11b-phenyl-2,3,7,11b-tetrahydro-benzo[f]oxazolo[3,2-d][1,4]diazepin-6-one (24111-44-2)

Conditions	Yield
With triethylamine In ethanol

2-(2-chloro-N-methyl-acetamido)-5-chlorobenzophenone (6021-21-2) → C19H19ClN2O4S

Conditions	Yield
Multi-step reaction with 5 steps 1.1: hexamethylenetetramine; ammonia / methanol / 6 h / 60 °C 2.1: lithium diisopropyl amide / tetrahydrofuran / 1 h / -78 °C 2.2: 3 h / -25 °C 3.1: ozone / dichloromethane / -78 °C 3.2: 0.08 h / -78 °C 3.3: 3 h / -78 - 25 °C 4.1: sodium tetrahydroborate / methanol / 1 h / 25 °C 5.1: triethylamine / dichloromethane / 1 h / 0 °C View Scheme

Upstream product

• 79-04-9 chloroacetyl chloride 
• 1022-13-5 5-chloro-2-(methylamino)benzophenone 

Downstream Products

• 59049-46-6 N-(2-Benzoyl-4-chloro-phenyl)-2-[butyl-(2-cyano-ethyl)-amino]-N-methyl-acetamide 
• 59049-39-7 N-(2-Benzoyl-4-chloro-phenyl)-2-(cyanomethyl-amino)-N-methyl-acetamide 
• 80356-39-4 1-(6-Chloro-1-methyl-2-oxo-4-phenyl-1,2-dihydro-quinolin-3-yl)-pyridinium; chloride 
• 24111-44-2 10-chloro-7-methyl-11b-phenyl-2,3,7,11b-tetrahydro-benzo[f]oxazolo[3,2-d][1,4]diazepin-6-one 
• 5220-02-0 3-amino-6-chloro-1,2-dihydro-1-methyl-2-oxo-4-phenylquinoline 
• 439-14-5 diazepam 
• 37393-79-6 6-chloro-1,2-dihydro-3-hydroxy-1-methyl-2-oxo-4-phenylquinoline 
• 37393-81-0 6-chloro-3,4-epoxy-1,2,3,4-tetrahydro-1-methyl-2-oxo-4-phenylquinoline 
• 59049-68-2 ({[(2-Benzoyl-4-chloro-phenyl)-methyl-carbamoyl]-methyl}-amino)-acetic acid methyl ester 
• 50840-32-9 N-(2-Benzoyl-4-chloro-phenyl)-2-[(2-cyano-2-methyl-ethyl)-methyl-amino]-N-methyl-acetamide 
• 59049-42-2 N-(2-Benzoyl-4-chloro-phenyl)-2-[(2-cyano-1-methyl-ethyl)-methyl-amino]-N-methyl-acetamide 

Relevant articles and documents

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