6967-29-9

Usage

Uses

Used in Pharmaceutical Industry:
N-CHLOROACETYL-2,6-DIETHYLANILINE is used as a reagent for the synthesis of novel inhibitors targeting the signal transducer and activator of the transcription (STAT3) signaling pathway. This pathway plays a crucial role in cell growth, differentiation, and apoptosis, and its dysregulation is often associated with various cancers. By inhibiting STAT3, these novel inhibitors can potentially contribute to the treatment of cancer.
Used in Chemical Synthesis:
N-CHLOROACETYL-2,6-DIETHYLANILINE can also be employed as an intermediate in the synthesis of various organic compounds, such as dyes, pigments, and other specialty chemicals. Its unique structural features make it a valuable building block for creating complex molecules with specific properties and applications.

InChI:InChI=1/C12H16ClNO/c1-3-9-6-5-7-10(4-2)12(9)14-11(15)8-13/h5-7H,3-4,8H2,1-2H3,(H,14,15)

Synthetic route

2,6-diethylaniline (579-66-8) + chloroacetyl chloride (79-04-9) → 2-chloro-2',6'-diethylacetanilide (6967-29-9)

Conditions	Yield
In ethyl acetate for 2h; Acylation; Heating;	99.1%
With triethylamine In dichloromethane at 0 - 20℃; for 6h;	82.72%
sodium acetate In acetic acid at 0℃; for 0.5h; Acylation;

Chloroiodomethane (593-71-5) + 2,6-diethylphenylisocyanate (20458-99-5) → 2-chloro-2',6'-diethylacetanilide (6967-29-9)

Conditions	Yield
With methyllithium lithium bromide In diethyl ether at -78℃;	95%
With methyllithium; lithium bromide In diethyl ether at -78℃; for 0.5h; chemoselective reaction;	95%

Alachlor (15972-60-8) → 2-chloro-2',6'-diethylacetanilide (6967-29-9)

Conditions	Yield
With hydrogenchloride In acetone for 4h; Hydrolysis; Heating;

2,6-diethylaniline (579-66-8) + chloroacetyl chloride (79-04-9) → 2-chloro-2',6'-diethylacetanilide (6967-29-9)

Conditions	Yield
In ethyl acetate for 2h; Acylation; Heating;	99.1%
With triethylamine In dichloromethane at 0 - 20℃; for 6h;	82.72%
sodium acetate In acetic acid at 0℃; for 0.5h; Acylation;

Chloroiodomethane (593-71-5) + 2,6-diethylphenylisocyanate (20458-99-5) → 2-chloro-2',6'-diethylacetanilide (6967-29-9)

Conditions	Yield
With methyllithium lithium bromide In diethyl ether at -78℃;	95%
With methyllithium; lithium bromide In diethyl ether at -78℃; for 0.5h; chemoselective reaction;	95%

Alachlor (15972-60-8) → 2-chloro-2',6'-diethylacetanilide (6967-29-9)

Conditions	Yield
With hydrogenchloride In acetone for 4h; Hydrolysis; Heating;

2-chloro-2',6'-diethylacetanilide (6967-29-9) + potassium phtalimide (1074-82-4) → 2-amino-2',6'-diethylacetanilide (70752-53-3)

Conditions	Yield
In N-methyl-acetamide	92%

1-ethoxy-2-chloromethoxyethane (69602-59-1) + 2-chloro-2',6'-diethylacetanilide (6967-29-9) → 2-Chloro-N-(2,6-diethyl-phenyl)-N-(2-ethoxy-ethoxymethyl)-acetamide (85211-82-1)

Conditions	Yield
With sodium hydroxide; PEG-400 In benzene at 15℃; for 2h;	90%

7-Hydroxy-2,2,5-trimethyl-4-chromanone (20052-60-2) + 2-chloro-2',6'-diethylacetanilide (6967-29-9) → N-(2,6-Diethyl-phenyl)-2-(2,2,5-trimethyl-4-oxo-chroman-7-yloxy)-acetamide (133035-38-8)

Conditions	Yield
With potassium carbonate; sodium iodide In acetone for 6h; Heating;	86.4%

2,3-dihydro-7-hydroxy-6-methoxy-2,2-dimethyl-4H-1-benzopyran-4-one (74094-45-4) + 2-chloro-2',6'-diethylacetanilide (6967-29-9) → N-(2,6-Diethyl-phenyl)-2-(6-methoxy-2,2-dimethyl-4-oxo-chroman-7-yloxy)-acetamide (133035-55-9)

Conditions	Yield
With potassium carbonate; sodium iodide In acetone for 6h; Heating;	80.3%

diisopropoxymethane (2568-89-0) + 2-chloro-2',6'-diethylacetanilide (6967-29-9) → 2-Chloro-N-(2,6-diethyl-phenyl)-N-isopropoxymethyl-acetamide (67535-24-4)

Conditions	Yield
With toluene-4-sulfonic acid for 5h; Heating;	60%

benzo[f]quinoline (85-02-9) + 2-chloro-2',6'-diethylacetanilide (6967-29-9) + propynoic acid ethyl ester (623-47-2) → ethyl 3-[N-(2,6-diethylphenyl)carbamoyl]benzo[f]pyrrolo[1,2-a]quinoline-1-carboxylate

Conditions	Yield
With ethyloxirane at 120℃; for 2h; Sealed tube; Microwave irradiation;	39%
With ethyloxirane at 120℃; for 2h; Sealed tube; Microwave irradiation;	39%

2-chloro-2',6'-diethylacetanilide (6967-29-9) + thymidine 3'-monophosphate disodium salt → 3-[[N-(2,6-diethylphenyl)carbamoyl]methyl]thymidine 3'-monophosphate disodium salt

Conditions	Yield
With sodium hydrogencarbonate In 2-methoxy-ethanol; water at 82℃; for 24h; Addition;	36.2%

2-chloro-2',6'-diethylacetanilide (6967-29-9) + thymidine (50-89-5) → 3-[[N-(2,6-diethylphenyl)carbamoyl]methyl]thymidine

Conditions	Yield
With sodium hydrogencarbonate In 2-methoxy-ethanol at 45 - 50℃; for 336h; Addition;	26%

2-chloro-2',6'-diethylacetanilide (6967-29-9) + 2'-deoxyguanosine 3'-monophosphate disodium salt → 1-[[N-(2,6-diethylphenyl)carbamoyl]methyl]-2'-deoxyguanosine 3'-monophosphate

Conditions	Yield
With sodium hydrogencarbonate In 2-methoxy-ethanol; water at 75℃; for 24h; Addition;	14.7%

2-chloro-2',6'-diethylacetanilide (6967-29-9) + 2'-Deoxyguanosine (961-07-9) → 1-[[N-(2,6-diethylphenyl)carbamoyl]methyl]-2'-deoxyguanosine

Conditions	Yield
With sodium hydrogencarbonate In 2-methoxy-ethanol at 45 - 50℃; for 336h; Addition;	12%

Chlorodifluoromethane (75-45-6) + 2-chloro-2',6'-diethylacetanilide (6967-29-9) → 1-(2,6-diethylphenyl)-4,4-difluoro-2-azetidinone (145143-43-7) + 1,4-bis(diethylphenyl)-2,5-piperazinedione (145143-47-1)

Conditions	Yield
With sodium hydride 1) THF, hexane, 1 h, 2) THF, 50 deg C; Yield given. Multistep reaction. Yields of byproduct given;

chloromethyl propyl ether (3587-57-3) + 2-chloro-2',6'-diethylacetanilide (6967-29-9) → N-butoxymethyl-alpha-chloro-2',6'-diethylacetanilide (67535-25-5)

Conditions	Yield
With sodium hydroxide; PEG-400 In benzene at 15℃; for 2h; Yield given;

isopropoxymethyl chloride (3587-58-4) + 2-chloro-2',6'-diethylacetanilide (6967-29-9) → 2-Chloro-N-(2,6-diethyl-phenyl)-N-isopropoxymethyl-acetamide (67535-24-4)

Conditions	Yield
With sodium hydroxide; PEG-400 In benzene at 15℃; for 2h; Yield given;

chloromethyl isobutyl ether (34180-11-5) + 2-chloro-2',6'-diethylacetanilide (6967-29-9) → 2-Chloro-N-(2,6-diethyl-phenyl)-N-isobutoxymethyl-acetamide (33717-32-7)

Conditions	Yield
With sodium hydroxide; PEG-400 In benzene at 15℃; for 2h; Yield given;

2-chloro-2',6'-diethylacetanilide (6967-29-9) + (methoxy-ethoxy)-methyl chloride (85232-18-4) → 2-Chloro-N-(2,6-diethyl-phenyl)-N-(1-methoxy-ethoxymethyl)-acetamide (85232-16-2)

Conditions	Yield
With sodium hydroxide; PEG-400 In benzene at 15℃; for 2h; Yield given;

2-chloro-2',6'-diethylacetanilide (6967-29-9) + chloromethyl methyl ether (107-30-2) → Alachlor (15972-60-8)

Conditions	Yield
With sodium hydroxide; PEG-400 In benzene at 15℃; for 2h; Yield given;

2-chloro-2',6'-diethylacetanilide (6967-29-9) + 1-(chloromethoxy)butane (2351-69-1) → N-butoxymethyl-2-chloro-N-(2,6-diethylphenyl)acetamide (23184-66-9)

Conditions	Yield
With sodium hydroxide; PEG-400 In benzene at 15℃; for 2h; Yield given;

2-chloro-2',6'-diethylacetanilide (6967-29-9) → 2-Hydroxy-N-(2,6-diethylphenyl)acetamide (52559-52-1)

Conditions	Yield
With sodium hydroxide In acetone for 8h; Substitution; Heating;
With aq. NaCO3 In ethanol for 6h; Hydrolysis;

Upstream product

• 579-66-8 2,6-diethylaniline 
• 79-04-9 chloroacetyl chloride 
• 593-71-5 Chloroiodomethane 
• 20458-99-5 2,6-diethylphenylisocyanate 
• 15972-60-8 Alachlor 

Downstream Products

• 133035-55-9 N-(2,6-Diethyl-phenyl)-2-(6-methoxy-2,2-dimethyl-4-oxo-chroman-7-yloxy)-acetamide 
• 133035-34-4 N-(2,6-Diethyl-phenyl)-2-(2,2-dimethyl-4-oxo-chroman-7-yloxy)-acetamide 
• 67535-25-5 N-butoxymethyl-alpha-chloro-2',6'-diethylacetanilide 
• 67535-24-4 2-Chloro-N-(2,6-diethyl-phenyl)-N-isopropoxymethyl-acetamide 
• 33717-32-7 2-Chloro-N-(2,6-diethyl-phenyl)-N-isobutoxymethyl-acetamide 
• 85211-82-1 2-Chloro-N-(2,6-diethyl-phenyl)-N-(2-ethoxy-ethoxymethyl)-acetamide 
• 85232-11-7 2-Chloro-N-(2,6-diethyl-phenyl)-N-(2-methoxy-ethoxymethyl)-acetamide 
• 133035-50-4 N-(2,6-Diethyl-phenyl)-2-(7-methoxy-2,2-dimethyl-4-oxo-chroman-6-yloxy)-acetamide 
• 131859-77-3 2-(7-Benzyloxy-2,2-dimethyl-4-oxo-chroman-6-yloxy)-N-(2,6-diethyl-phenyl)-acetamide 
• 85232-16-2 2-Chloro-N-(2,6-diethyl-phenyl)-N-(1-methoxy-ethoxymethyl)-acetamide 
• 85232-14-0 2-Chloro-N-(2,6-diethyl-phenyl)-N-[2-(2-ethoxy-ethoxy)-ethoxymethyl]-acetamide 
• 104310-90-9 (2,6-Diethyl-phenyl)-phosphoramidic acid diethyl ester 
• 145143-46-0 2-iodo-N-<2,6-diethylphenyl>acetamide 
• 23184-66-9 N-butoxymethyl-2-chloro-N-(2,6-diethylphenyl)acetamide 

Relevant academic research and scientific papers

Synthesis and Characterization of Adducts of Alachlor and 2-Chloro-N-(2,6-diethylphenyl)acetamide with 2'-Deoxyguanosine, Thymidine, and Their 3'-Monophosphates

Adducts of the preemergence herbicide 2-chloro-N-(methoxymethyl)-N-(2,6-diethylphenyl)acetamide (alachlor) and 2-chloro-N-(2,6-diethylphenyl)acetamide (CDEPA) with 2'-deoxyguanosine, thymidine, 2'-deoxyguanosine 3'-monophosphate, and thymidine 3'-monophosphate have been synthesized and characterized. Under mildly basic conditions alachlor and CDEPA form N-1 adducts with 2'-deoxyguanosine and N-3 adducts with thymidine as a result of chlorine displacement. In addition, alachlor formed an N-7 adduct with 2'-deoxyguanosine, 7-[[(N-(methoxymethyl)-N-(2,6-diethylphenyl)carbamoyl]methyl]guanine. N-1 adducts of alachlor and CDEPA with 2'-deoxyguanosine 3'-monophosphate and N-3 adducts with thymidine 3'-monophosphate are also described. In addition to spectroscopic data, structural proof included the dephosphorylation of each nucleotide adduct to its corresponding nucleoside adduct by nuclease P1. Alachlor and alachlor adducts but not CDEPA and CDEPA adducts exhibited rotational isomerism as evidenced by proton and 13C NMR studies. These rotamers were attributed to hindered rotation about the shortened N-carbonyl bond. Computational methods employing molecular mechanics and quantum mechanics were used to characterize the structures and energies of these rotamers to account for the patterns of duplicate NMR resonances observed.

Microwave-assisted multicomponent synthesis of benzo[f]pyrrolo[1,2-a]quinoline derivatives

We present an efficient one-pot, three component microwave-assisted synthesis of benzo[f]pyrrolo[1,2-a]quinoline derivatives starting from benzo[f]quinoline, 2-bromo-acetophenones or 2-chloro-(N-phenyl)acetamides and electron-deficient alkynes. This synthetic strategy provides a direct and easy access to a range of novel benzo[f]pyrrolo[1,2-a]quinoline derivatives. The method has the advantages of considerable shorter reaction time, reduced solvent consumption, operational simplicity and minimal impact on the environment. Nine new benzo[f]pyrrolo[1,2-a]quinoline derivatives have been synthesized with the new method and they are fully characterized.

Microwave-Assisted multicomponent synthesis of benzo[f]pyrrolo[1,2-a]quinoline derivatives

We present an efficient one-pot, three component microwave-assisted synthesis of benzo[f]pyrrolo[1,2-a]quinoline derivatives starting from benzo[f]quinoline, 2-bromo-acetophenones or 2-chloro-(N-phenyl)acetamides and electron-deficient alkynes. This synthetic strategy provides a direct and easy access to a range of novel benzo[f]pyrrolo[1,2-a]quinoline derivatives. The method has the advantages of considerable shorter reaction time, reduced solvent consumption, operational simplicity and minimal impact on the environment. Nine new benzo[f]pyrrolo[1,2-a]quinoline derivatives have been synthesized with the new method and they are fully characterized.

Anti-proliferative activity, molecular modeling studies and interaction with calf thymus DNA of novel ciprofloxacin analogues

Abstract: In our pursuit to expand new potential anticancer leads, a series of eighteen novel 1-cyclopropyl-6-fluoro-4-oxo-7-(4-substituted piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid analogues have been synthesized, characterized and evaluated anti-proliferative activity against five human cancer cell lines such as A549 (lung cancer), Mia Paca (pancreatic cancer), HeLa (cervical cancer), MDA MB-231 (breast cancer), MCF-7 (breast cancer) and normal embryonic kidney?cell line (HEK) were carried out using MTT assay. Few of the synthesized analogues exhibited potent anticancer activity against the cancer cell lines at a lower concentration. The synthesized compounds showed the less toxic effect on normal human embryonic kidney?cell line (HEK) compared with doxorubicin. Noticeably, compound 3o exhibited potent activity against all five cancer cell lines compared with ciprofloxacin. Further study exposed that compound 3o could competently intercalate into calf thymus DNA to form 3o-DNA complex which might block DNA replication to apply anti-proliferative activity. Docking simulation studies supported by molecular interactions with DNA type II topoisomerase. These derivates can become lead structures for the development of potential anticancer drugs. Graphical Abstract: Eighteen CP analogues were synthesized and evaluated for anti-proliferative activity. The interactions with DNA topoisomerase II were supported by molecular docking studies. 3o showed promising anticancer activity than CP against MCF7 cell line and interaction with calf thymus DNA was studied by fluorescence spectroscopy.[Figure not available: see fulltext.].

Quaternary ammonium salt compound and application thereof

Belonging to the field of agricultural herbicides, the invention in particular relates to a quaternary ammonium salt compound and application thereof. The quaternary ammonium salt compound is shown as general formula (I). The general formula (I) compound has very good herbicidal activity, can effectively control barnyard grass, Abutilon theophrasti, Green Bristlegrass Herb, Zinnia elegans and other weeds, can achieve a good weeding effect under a low dosage, and is safe to corn and cotton before emergence and safe to wheat and corn after emergence. (general formula (I)).

Homologation of isocyanates with lithium carbenoids: A straightforward access to α-halomethyl- and α,α-dihalomethylamides

Treatment of widely available isocyanates with monohalolithium and dihalolithium carbenoids provides a valuable protocol for the one-pot preparation of α-halo- and α,α-dihaloacetamide derivatives. While monohalolithium carbenoids can be prepared by a smoo

Addition of lithium carbenoids to isocyanates: A direct access to synthetically useful N-substituted 2-haloacetamides

The addition of lithium carbenoids to isocyanates provides a versatile access to N-substituted 2-haloacetamides: the reaction tolerates the presence of variously functionalized substituents on the nitrogen atom, including sterically demanding ones and reactive halogens. No erosion of the enantiopurity was observed in the case of optically active isocyanates. One of the substrates prepared has been employed in Charette's type chemoselective addition of a Grignard reagent to access an α-chloroketone.

Discovery of novel inhibitors of signal transducer and activator of transcription 3 (STAT3) signaling pathway by virtual screening

Inhibition of the signal transducer and activator of transcription 3 (STAT3) signaling pathway has been considered a novel therapeutic strategy to treat human cancers that harbor aberrantly-active STAT3. In this study, nearly 204,000 compounds in Specs database were screened by virtual screening, and samples of top 100 compounds identified as candidate small-molecule inhibitors of STAT3 were evaluated by STAT3-dependent luciferase reporter assay as well as other cell-based assays. A benzothiazole core scaffold containing compound, 9, was identified as an inhibitor of IL-6/STAT3 signaling with an IC50 of 3.567 μM. It is the first time to discover benzothiazole scaffold as a potent STAT3 signaling inhibitor. We further investigated the (structure-activity relationship) SAR of the benzothiazole analogues, and discovered compound 16w as a better small-molecule inhibitor. Both compounds inhibited the phosphorylation of STAT3 and had no obvious effect on upstream JAK2 kinase.

Synthesis, glucose uptake activity and structure-activity relationships of some novel glitazones incorporated with glycine, aromatic and alicyclic amine moieties via two carbon acyl linker

Three series of novel glitazones were designed and prepared by using appropriate synthetic schemes to incorporate glycine, aromatic and alicyclic amines via two carbon linker. Compounds were synthesized both under conventional and microwave methods. Nineteen out of twenty four synthesized compounds were evaluated for their in vitro glucose uptake activity using isolated rat hemi-diaphragm. Compounds, 6, 9a, 13a, 13b, 13c, 13f and 13h exhibited significant glucose uptake activity. Illustration about their synthesis and in vitro glucose uptake activity is described along with the structure-activity relationships.

Synthesis and biological evaluation of 1,4-diazepane derivatives as T-type calcium channel blockers

We have synthesized and biologically evaluated 1,4-diazepane derivatives as T-type calcium channel blockers. In this study, we discovered compound 4s, a potential T-type calcium channel blocker with good selectivity over hERG and N-type calcium channels. In addition, it exhibited favorable pharmacokinetic characteristics for further investigation of T-type calcium channel related diseases.