2632-13-5

Basic information

• Product Name: 2-Bromo-4'-methoxyacetophenone
• Synonyms: Bromomethyl 4-methoxyphenyl ketone;4-(BROMOACETYL)ANISOLE;4-methoxy phenecyl bromide;4-METHOXYPHENACYL BR;4'-METHOXYPHENACYL BROMIDE;4-METHOXYPHENACYL BROMIDE;A-BROMO-P-METHOXYACETOPHENONE;ALPHA-BROMO-4'-METHOXYACETOPHENONE
• CAS NO: 2632-13-5
• Molecular Formula: C₉H₉BrO₂
• Molecular Weight: 229.07
• EINECS: 220-118-8
• Product Categories: Protection & Derivatization Reagents (for Synthesis);Synthetic Organic Chemistry
• Mol File: 2632-13-5.mol
• Article Data: 132

Chemical Properties

• Melting Point: 69-71 °C(lit.)
• Boiling Point: 215.8°C (rough estimate)
• Flash Point: 139.3 °C
• Appearance: Off-white to light brown/Crystals or Crystalline Powder
• Density: 1.4921 (rough estimate)
• Vapor Pressure: 0.00076mmHg at 25°C
• Refractive Index: 1.5500 (estimate)
• Storage Temp.: 2-8°C
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• Water Solubility: It is soluble in DMSO, water (partly miscible), most organic solvents, and methanol.
• BRN: 743112
• CAS DataBase Reference: 2-Bromo-4'-methoxyacetophenone(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Bromo-4'-methoxyacetophenone(2632-13-5)
• EPA Substance Registry System: 2-Bromo-4'-methoxyacetophenone(2632-13-5)

Safety Data

• Hazard Codes: C,Xi
• Statements: 34-36/37-36/37/38
• Safety Statements: 26-27-28-36/37/39-45-37/39
• RIDADR: UN 3261 8/PG 2
• WGK Germany: 3
• F: 8-9-19-21
• HazardClass: 8
• PackingGroup: III
• Hazardous Substances Data: 2632-13-5(Hazardous Substances Data)

Usage

Chemical Properties

off-white to light brown crystals or

Uses

Different sources of media describe the Uses of 2632-13-5 differently. You can refer to the following data:
1. 2-Bromo-4'-methoxyacetophenone is a α-haloacetophenone derivatives tested for inhibition of protein tyrosine phosphatases SHP-1 and PTP1B.
2. 2-Bromo-4'-methoxyacetophenone, is used as a cell-permeable, covalent and potent protein tyrosine phosphatase inhibitor.

Preparation

Obtained by reaction of N-bromosuccinimide (NBS) with 4-methoxyacetophenone in the presence of trimethylsilyl trifluoromethanesulfonate (TMS-OTf) in acetonitrile at r.t. for 24 h (87%).

Biological Activity

ki: 128 μmptp inhibitor ii is a protein tyrosine phosphatase (ptp) inhibitor.protein tyrosine phosphatases (ptps) are reported to be involved in the etiology of diabetes mellitus, neural diseases such as alzheimer and parkinson diseases, regulation of allergy and inflammation, or ptps are even regarded to be responsible for the pathogens.

in vitro

in a previous study, it was found that all of the previously reported ptp inhibitors contained a negatively charged, nonhydrolyzable py mimetic as the core structure, such as malonates, aryl carboxylates, phosphonates, or cinnamates. the poor membrane permeability of these inhibitors might compromise their potential development. it was reported that several α-bromoacetophenone derivatives, such as ptp inhibitor ii, could act as fairly potent ptp inhibitors, by covalently alkylating the conserved catalytic cysteine in the ptp active site. since ptp inhibitor ii is neutral, it could readily diffuse into human b cells and inhibit the intracellular ptps. the sar study was performed with the catalytic domain of phosphatase shp-1, and ti was found that ptp inhibitor ii showed time-dependent inactivation of shp-1, consistent with the mechanism. furthermore, the potency of ptp inhibitor ii was described by an equilibrium constant ki, representing the dissociation constant of the noncovalent enzyme–inhibitor complex. ptp inhibitor ii bound with lower affinity than ptp inhibitor i with ki values of 128 μm [1].

references

[1] p. heneberg. use of protein tyrosine phosphatase inhibitors as promising targeted therapeutic drugs. current medicinal chemistry 16(6), 706-733 (2009).

InChI:InChI=1/C9H9BrO2/c1-12-8-4-2-7(3-5-8)9(11)6-10/h2-5H,6H2,1H3

Synthetic route

1-(4-methoxyphenyl)ethanone (100-06-1) → 2-Bromo-4'-methoxyacetophenone (2632-13-5)

Conditions	Yield
With bromine In 1,4-dioxane; diethyl ether for 0.5h; Ambient temperature;	100%
With N-Bromosuccinimide; toluene-4-sulfonic acid In chloroform at 20℃; for 12h;	98.7%
With bis(dimethylacetamide)hydrogen tribromide In methanol at 20 - 45℃; for 0.25h;	96%

1-bromo-2-(4-methoxyphenyl)acetylene (33675-41-1) → 2-Bromo-4'-methoxyacetophenone (2632-13-5)

Conditions	Yield
With tetrafluoroboric acid; water In 2,2,2-trifluoroethanol at 80℃; for 2h;	93%
With indium(III) triflate; water In acetic acid at 100℃; Sealed tube;	92%
With cerium(IV) sulphate; sulfuric acid; water In dichloromethane at 80℃; for 12h; Sealed tube; regioselective reaction;	90%

4-methoxyphenylacetylen (768-60-5) → 2-Bromo-4'-methoxyacetophenone (2632-13-5)

Conditions	Yield
With N,N'-ethylenethiourea; 1,3-dibromo-5,5-dimethylhydantoin; water In acetone at 45℃;	87%
Stage #1: 4-methoxyphenylacetylen With methanol; gold(III) chloride; silver(I) triflimide In 1,4-dioxane at 45℃; Stage #2: With N-Bromosuccinimide In 1,4-dioxane regioselective reaction;	75%
Multi-step reaction with 2 steps 1: diethyl ether / Umsetzen der entstandenen Magnesiumverbindung mit Bromcyan 2: sulfuric acid View Scheme
Multi-step reaction with 2 steps 1: N-Bromosuccinimide; silver nitrate / acetone / 20 °C 2: water; 2-(dicyclohexylphosphino)-2',4',6'-triisopropylbiphenyl Au bis(trifluoromethylsulfonyl)imide / 1,2-dichloro-ethane / 14 h / 20 °C View Scheme

2,2-dibromo-1-(4-methoxyphenyl)ethanone (13664-92-1) → 2-Bromo-4'-methoxyacetophenone (2632-13-5)

Conditions	Yield
With tris(2,2'-bipyridyl)ruthenium dichloride; 1,5-dimethoxynaphthalene; ascorbic acid In methanol; water for 2h; Inert atmosphere; Irradiation;	70%

4-Methoxystyrene (637-69-4) → 2-Bromo-4'-methoxyacetophenone (2632-13-5)

Conditions	Yield
With ferric(III) bromide; oxygen; toluene-4-sulfonic acid; potassium bromide In tert-butyl methyl ether at 20℃; Irradiation; Green chemistry;	65%
With dipotassium peroxodisulfate; potassium bromide In water at 60℃; for 12h; Green chemistry;	24%
Multi-step reaction with 2 steps 1: N-Bromosuccinimide / acetonitrile; water / 4 h / 25 - 30 °C 2: 2-iodo-3,4,5,6-tetramethylbenzoic acid; oxone / acetonitrile; water / 10 h / 25 - 30 °C View Scheme
With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; water In acetone at 70℃; for 0.138833h;

1-(4-methoxyphenyl)ethanone (100-06-1) → 2,2-dibromo-1-(4-methoxyphenyl)ethanone (13664-92-1) + 2-Bromo-4'-methoxyacetophenone (2632-13-5)

Conditions	Yield
With N-Bromosuccinimide; silica gel In methanol for 0.216667h; Reflux; chemoselective reaction;	A n/a B 64%
With 1-methyl-3-(4-sulfonylbutyl)-1H-imidazol-3-ium trifluoromethanesulfonate; N-Bromosuccinimide at 55℃; for 0.333333h; Green chemistry;	A 20% B 62%
With potassium permanganate; hydrogen bromide In acetonitrile at 60℃;	A 6% B 56%

4-methoxy-α-bromoacetophenone oxime (14181-83-0) → 2-Bromo-4'-methoxyacetophenone (2632-13-5)

Conditions	Yield
With oxygen; sodium nitrite In dichloromethane; water at 25℃; under 760.051 Torr; for 6h; Sealed system;	52%

2-(4-methoxyphenyl)-2-methyI-1,3-dioxolane (36881-00-2) → 2-bromomethyl-2-(4-methoxyphenyl)-1,3-dioxolane (4366-28-3) + 2-Bromo-4'-methoxyacetophenone (2632-13-5)

Conditions	Yield
With phenyltrimethylammonium tribromide In tetrahydrofuran at 25℃; for 2.15h;	A 50% B 50 % Chromat.

1-bromo-2-(4-methoxyphenyl)acetylene (33675-41-1) + acetic acid (64-19-7) → 2-Bromo-4'-methoxyacetophenone (2632-13-5)

Conditions	Yield
With sulfuric acid

methoxybenzene (100-66-3) + 2-Bromoacetyl bromide (598-21-0) → 2-Bromo-4'-methoxyacetophenone (2632-13-5)

Conditions	Yield
With carbon disulfide; aluminium trichloride

methanol (67-56-1) + 2,2,2-tribromo-1-(4-methoxyphenyl)ethan-1-one → 2,2-dibromo-1-(4-methoxyphenyl)ethanone (13664-92-1) + methyl 4-methoxybenzoate (121-98-2) + 4-methoxyphenylglyoxylate methyl ester (32766-61-3) + 2-Bromo-4'-methoxyacetophenone (2632-13-5)

Conditions	Yield
With oxygen at 10℃; for 2h; Irradiation;	A 5.8 % Chromat. B 4.4 % Chromat. C 61.9 % Chromat. D 1 % Chromat.

2-(4-methoxyphenyl)-2-methyI-1,3-dioxolane (36881-00-2) → 2,2-dibromo-1-(4-methoxyphenyl)ethanone (13664-92-1) + 2-Bromo-4'-methoxyacetophenone (2632-13-5)

Conditions	Yield
With tribromure de triphenylmethylphosphonium In dichloromethane at 25℃; for 3h;	A 15 % Chromat. B 70 % Chromat.

3-Bromomethyl-3-(4-methoxy-phenyl)-4,4-dimethyl-[1,2]dioxetane (108773-86-0) → acetone (67-64-1) + 2-Bromo-4'-methoxyacetophenone (2632-13-5)

Conditions	Yield
In xylene at 60℃; Thermodynamic data; Rate constant; Ea; other solvents and temp., var. 1,2-dioxetanes;

4-methoxy-α-bromoacetophenone methyl hemiacetal (119205-35-5) → methanol (67-56-1) + 2-Bromo-4'-methoxyacetophenone (2632-13-5)

Conditions	Yield
With hydrogen cation In water at 25℃; Rate constant;
With hydroxide In water at 25℃; Rate constant;
With water at 25℃; Rate constant;
With acetate In water at 25℃; Rate constant;

ethyl 4-methoxybenzoate (94-30-4) + 1,1-dibromomethane (74-95-3) → 2-Bromo-4'-methoxyacetophenone (2632-13-5)

Conditions	Yield
With n-butyllithium; lithium diisopropyl amide Yield given. Multistep reaction;

1-((E)-2-Bromo-1-methoxy-vinyl)-4-methoxy-benzene → 2-Bromo-4'-methoxyacetophenone (2632-13-5)

Conditions	Yield
With sulfuric acid Ambient temperature; Yield given;

2-diazo-1-<4-methoxy-phenyl>-ethanone-(1) → 2-Bromo-4'-methoxyacetophenone (2632-13-5)

Conditions	Yield
With diethyl ether; hydrogen bromide

1-((4-methoxy)phenyl)-1,2-dibromoethane (19484-05-0) → 2-Bromo-4'-methoxyacetophenone (2632-13-5)

Conditions	Yield
Stage #1: 1-((4-methoxy)phenyl)-1,2-dibromoethane With water at 100℃; for 3h; Stage #2: With dihydrogen peroxide In 1,4-dioxane; water at 25℃; for 3h;	41 %Chromat.

2-chloro-1-(4-methoxyphenyl)ethanone (2196-99-8) → 2-Bromo-4'-methoxyacetophenone (2632-13-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: tris(2,2'-bipyridyl)ruthenium dichloride; 1,5-dimethoxynaphthalene; ascorbic acid / methanol; water / 15 h / Inert atmosphere; Irradiation 2: bromine / chloroform / 0 - 65 °C View Scheme

4-Hydroxyacetophenone (99-93-4) → 2-Bromo-4'-methoxyacetophenone (2632-13-5)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: potassium carbonate / acetone / 0.25 h / Reflux 1.2: 3 h / Reflux 2.1: bromine; acetic acid / 50 °C View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / acetone / 2 h / Reflux 2: hydrogenchloride; bromine / methanol / 3 h / 0 - 20 °C View Scheme
Multi-step reaction with 2 steps 1.1: potassium carbonate / acetone / 0.25 h / Reflux 1.2: 3 h / Reflux 2.1: bromine; acetic acid / 50 °C View Scheme

thiourea (17356-08-0) + 1-(4-methoxyphenyl)ethanone (100-06-1) → 2-Bromo-4'-methoxyacetophenone (2632-13-5)

Conditions	Yield
With copper(ll) bromide In ethanol for 2h; Reflux;

2-bromo-1-(4-methoxyphenyl)ethanol (117340-79-1) → 2-Bromo-4'-methoxyacetophenone (2632-13-5)

Conditions	Yield
With oxone; 2-iodo-3,4,5,6-tetramethylbenzoic acid In water; acetonitrile at 25 - 30℃; for 10h;	139 mg

para-bromoacetophenone (99-90-1) → 2-Bromo-4'-methoxyacetophenone (2632-13-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: copper(l) iodide; potassium carbonate / N,N-dimethyl-formamide / Reflux 2: copper(ll) bromide / ethyl acetate; chloroform / Reflux View Scheme

4-methoxybenzoic acid (100-09-4) → 2-Bromo-4'-methoxyacetophenone (2632-13-5)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 1 h / 0 °C / Inert atmosphere 2.1: 1 h / 0 °C 2.2: 0.33 h / 0 °C View Scheme

diazomethane (186581-53-3, 908094-01-9) + 4-methoxy-benzoyl chloride (100-07-2) → 2-Bromo-4'-methoxyacetophenone (2632-13-5)

Conditions	Yield
Stage #1: diazomethane; 4-methoxy-benzoyl chloride at 0℃; for 1h; Stage #2: With hydrogen bromide at 0℃; for 0.333333h;

N-Bromosuccinimide (128-08-5) + 1-(4-methoxyphenyl)ethanone (100-06-1) → 2-Bromo-4'-methoxyacetophenone (2632-13-5)

Conditions	Yield
With toluene-4-sulfonic acid at 60 - 80℃;

thioacetamide (62-55-5) + 2-Bromo-4'-methoxyacetophenone (2632-13-5) → methyl 4-(2-methyl-1,3-thiazol-4-yl)phenyl ether (50834-78-1)

Conditions	Yield
In ethanol for 2h; Reflux;	100%
In ethylene glycol at 20℃; for 0.0833333h;	97%
With 1,3-di-n-butyl-imidazolium tetrafluoroborate at 20℃; for 0.25h;	96%

tris<(trimethylsiloxy)methyl>phosphine (63245-87-4) + 2-Bromo-4'-methoxyacetophenone (2632-13-5) → [2-(4-Methoxy-phenyl)-2-oxo-ethyl]-tris-trimethylsilanyloxymethyl-phosphonium; bromide (75532-43-3)

Conditions	Yield
at 20℃; for 5h;	100%

2-Bromo-4'-methoxyacetophenone (2632-13-5) → 1-(4-methoxyphenyl)ethanone (100-06-1)

Conditions	Yield
With AcrH2 In acetonitrile at 298℃; for 19h; Irradiation;	100%
With AcrH2 In acetonitrile at 298℃; for 19h; Irradiation;	100%
With decaborane; palladium on activated charcoal In methanol at 20℃; for 2h;	99%

sodium 4-methylbenzenesulfinate (824-79-3) + 2-Bromo-4'-methoxyacetophenone (2632-13-5) → 1-(4-methoxyphenyl)-2-tosylethanone (86516-51-0)

Conditions	Yield
In 1,4-dioxane; water Reflux;	100%
In ethanol for 1.5h; Heating;	90%
In ethanol Heating;

thiourea (17356-08-0) + 2-Bromo-4'-methoxyacetophenone (2632-13-5) → 4-(4-methoxyphenyl)-1,3-thiazol-2-amine (2104-04-3)

Conditions	Yield
In ethanol at 45℃; for 0.333333h; Sonication;	100%
In ethanol for 2h; Reflux;	100%
In ethanol for 1h; Reflux;	99%

2-Bromo-4'-methoxyacetophenone (2632-13-5) + dimethyl 3,4-bis(4-(benzyloxy)phenyl)-1H-pyrrole-2,5-dicarboxylate (220230-81-9) → dimethyl 3,4-bis(4-benzyloxyphenyl)-1-<2-(4-methoxyphenyl)-2-oxoethyl>pyrrole-2,5-dicarboxylate (220230-84-2)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 70℃; for 1h;	100%

2-Bromo-4'-methoxyacetophenone (2632-13-5) → 1-(4-Methoxy-phenyl)-2-nitrooxy-ethanone (66702-78-1)

Conditions	Yield
With silver nitrate In acetonitrile at 20℃; for 10h;	100%
With silver nitrate In acetonitrile at 20℃; for 48h;

2-Iodophenol (533-58-4) + 2-Bromo-4'-methoxyacetophenone (2632-13-5) → 2-(2-iodophenoxy)-1-(4-methoxyphenyl)ethan-1-one (908119-67-5)

Conditions	Yield
With potassium carbonate In acetone at 80℃; for 4h;	100%
With potassium carbonate In acetone Reflux;	90%
With potassium carbonate	80%

6,7-dimethoxy-1-(2',2'-diphenyl-1'-ethenyl)-3,4-dihydroisoquinoline (537040-39-4) + 2-Bromo-4'-methoxyacetophenone (2632-13-5) → 6,7-dimethoxy-1-(2',2'-diphenyl-1-ethenyl)-2-[2-(4-methoxyphenyl)-2-oxoethyl]-3,4-dihydroisoquinolinium bromide

Conditions	Yield
In diethyl ether	100%

phenanthridine (229-87-8) + 2-Bromo-4'-methoxyacetophenone (2632-13-5) → 5-[2-(4-methoxy-phenyl)-2-oxo-ethyl]-phenanthridinium bromide

Conditions	Yield
In acetonitrile Heating;	100%
In acetonitrile Heating;

2-Bromo-4'-methoxyacetophenone (2632-13-5) → p-methoxyphenylglyoxal (1076-95-5)

Conditions	Yield
With dimethyl sulfoxide In water at 50℃; for 2.5h;	100%
Multi-step reaction with 2 steps 1: AgNO3 / acetonitrile / 48 h / 20 °C 2: 1.69 g / NaOAc / dimethylsulfoxide / 16 h / 20 °C View Scheme
In dimethyl sulfoxide

thiourea (17356-08-0) + 2-Bromo-4'-methoxyacetophenone (2632-13-5) → 4-(4-methoxyphenyl)thiazol-2-amine

Conditions	Yield
In acetone at 20℃;	100%

4-methoxy-aniline (104-94-9) + 2-Bromo-4'-methoxyacetophenone (2632-13-5) → C25H25NO5 (333306-69-7)

Conditions	Yield
With sodium carbonate decahydrate In ethanol Reflux;	100%

phenylglyoxylic acid potassium salt (63468-90-6) + 2-Bromo-4'-methoxyacetophenone (2632-13-5) → 2-(4-methoxyphenyl)-2-oxoethyl 2-oxo-2-phenylacetate

Conditions	Yield
In dimethyl sulfoxide at 20℃; for 0.5h; Inert atmosphere; Schlenk technique;	100%

potassium 2-(4-methoxyphenyl)-2-oxoacetate (278799-27-2) + 2-Bromo-4'-methoxyacetophenone (2632-13-5) → 2-(4-methoxyphenyl)-2-oxoethyl 2-(4-methoxyphenyl)-2-oxoacetate

Conditions	Yield
In dimethyl sulfoxide at 20℃; for 0.5h; Inert atmosphere; Schlenk technique;	100%

2-Bromo-4'-methoxyacetophenone (2632-13-5) + 4-methyl-N-{2-(phenylethynyl)phenyl}benzenesulfonamide (442155-91-1) → 4-methyl-N-(2-oxo-2-(p-tolyl)ethyl)-N-(2-(phenylethynyl)phenyl)benzenesulfonamide

Conditions	Yield
Stage #1: 4-methyl-N-{2-(phenylethynyl)phenyl}benzenesulfonamide With potassium carbonate In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: 2-Bromo-4'-methoxyacetophenone In N,N-dimethyl-formamide at 20℃;	100%
Stage #1: 4-methyl-N-{2-(phenylethynyl)phenyl}benzenesulfonamide With potassium carbonate In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: 2-Bromo-4'-methoxyacetophenone In N,N-dimethyl-formamide at 20℃;	90%

4-methyl-N-(4-methyl-2-(phenylethynyl)phenyl)benzenesulfonamide (946161-99-5) + 2-Bromo-4'-methoxyacetophenone (2632-13-5) → C31H27NO4S

Conditions	Yield
Stage #1: 4-methyl-N-(4-methyl-2-phenylethynyl-phenyl)-benzenesulfonamide With potassium carbonate In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: 2-Bromo-4'-methoxyacetophenone In N,N-dimethyl-formamide at 20℃;	100%

4-methyl-N-(4-fluoro-2-phenylethynyl-phenyl)-benzenesulfonamide (946162-00-1) + 2-Bromo-4'-methoxyacetophenone (2632-13-5) → C30H24FNO4S

Conditions	Yield
Stage #1: 4-methyl-N-(4-fluoro-2-phenylethynyl-phenyl)-benzenesulfonamide With potassium carbonate In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: 2-Bromo-4'-methoxyacetophenone In N,N-dimethyl-formamide at 20℃;	100%

4-methyl-N-(4-chloro-2-phenylethynyl-phenyl)-benzenesulfonamide (946162-01-2) + 2-Bromo-4'-methoxyacetophenone (2632-13-5) → C30H24ClNO4S

Conditions	Yield
Stage #1: 4-methyl-N-(4-chloro-2-phenylethynyl-phenyl)-benzenesulfonamide With potassium carbonate In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: 2-Bromo-4'-methoxyacetophenone In N,N-dimethyl-formamide at 20℃;	100%

4-methyl-N-(2-(p-tolylethynyl)phenyl)benzenesulfonamide (1236044-93-1) + 2-Bromo-4'-methoxyacetophenone (2632-13-5) → C31H27NO4S

Conditions	Yield
Stage #1: 4-methyl-N-(2-(p-tolylethynyl)phenyl)benzenesulfonamide With potassium carbonate In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: 2-Bromo-4'-methoxyacetophenone In N,N-dimethyl-formamide at 20℃;	100%

4-bromo-N-(2-(phenylethynyl)phenyl)benzenesulfonamide + 2-Bromo-4'-methoxyacetophenone (2632-13-5) → C29H22BrNO4S

Conditions	Yield
Stage #1: 4-bromo-N-(2-(phenylethynyl)phenyl)benzenesulfonamide With potassium carbonate In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: 2-Bromo-4'-methoxyacetophenone In N,N-dimethyl-formamide at 20℃;	100%

p-cresol (106-44-5) + 2-Bromo-4'-methoxyacetophenone (2632-13-5) → 1-(4-methoxyphenyl)-2-(p-tolyloxy)ethan-1-one (19803-05-5)

Conditions	Yield
With potassium carbonate In acetone at 20℃; for 4h; Reflux;	100%
With potassium carbonate In acetone at 20℃; for 16h; Inert atmosphere; Schlenk technique;

α-picoline (109-06-8) + 2-Bromo-4'-methoxyacetophenone (2632-13-5) → 2-(4-methoxyphenyl)-indolizine (7496-82-4)

Conditions	Yield
Stage #1: α-picoline; 2-Bromo-4'-methoxyacetophenone In acetone for 1h; Heating; Stage #2: With potassium carbonate for 5h;	99%

2-aminopyridine (504-29-0) + 2-Bromo-4'-methoxyacetophenone (2632-13-5) → 2-(4-methoxyphenyl)imidazo[1,2-a]pyridine (31562-99-9)

Conditions	Yield
In neat (no solvent) at 25 - 30℃; Milling; Green chemistry;	99%
at 20℃; for 0.166667h; grinding; neat (no solvent);	95%
In water; isopropyl alcohol at 75℃; Microwave irradiation; Green chemistry;	95%

2-Amino-4-methylpyridine (695-34-1) + 2-Bromo-4'-methoxyacetophenone (2632-13-5) → 2-(4-methoxyphenyl)-7-methyl-imidazo[1,2-a]pyridine (65964-63-8)

Conditions	Yield
In neat (no solvent) at 25 - 30℃; Milling; Green chemistry;	99%
In water; isopropyl alcohol at 75℃; Microwave irradiation; Green chemistry;	96%
In neat (no solvent) at 65℃; under 750.075 Torr; for 0.3h; Microwave irradiation; Green chemistry;	83%

benzylamine (100-46-9) + 2-Bromo-4'-methoxyacetophenone (2632-13-5) → 2-(benzylamino)-1-(4-methoxyphenyl)ethanone (347977-58-6)

Conditions	Yield
In tetrahydrofuran; diethyl ether at -78 - 20℃; for 3h; Inert atmosphere;	99%

4-amino-5-(pyridin-4-yl)-4H-1,2,4-triazole-3-thiol (36209-51-5) + 2-Bromo-4'-methoxyacetophenone (2632-13-5) → 6-(4-methoxyphenyl)-3-(pyridin-4-yl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine

Conditions	Yield
In ethanol at 95℃; for 0.5h; Microwave irradiation;	99%
Stage #1: 4-amino-5-(pyridin-4-yl)-4H-1,2,4-triazole-3-thiol; 2-Bromo-4'-methoxyacetophenone In ethanol for 2h; Reflux; Stage #2: With ammonium hydroxide In ethanol at 20℃;	78%
In ethanol for 24h; Heating;	62%

potassium cyanamide salt (29422-34-2) + 2-Bromo-4'-methoxyacetophenone (2632-13-5) → (4-Amino-2-ethoxy-thiazol-5-yl)-(4-methoxy-phenyl)-methanone (86690-10-0)

Conditions	Yield
With triethylamine In acetone for 2h; Ambient temperature;	99%

4-amino-5-(4-bromophenyl)-3-mercapto-1,2,4-triazole (85106-58-7) + 2-Bromo-4'-methoxyacetophenone (2632-13-5) → 3-(4-bromophenyl)-6-(4-methoxyphenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine

Conditions	Yield
In ethanol at 95℃; for 0.5h; Microwave irradiation;	99%
In ethanol for 24h; Heating;	82%

Upstream product

• 100-66-3 methoxybenzene 
• 598-21-0 2-Bromoacetyl bromide 
• 100-06-1 1-(4-methoxyphenyl)ethanone 
• 108773-86-0 3-Bromomethyl-3-(4-methoxy-phenyl)-4,4-dimethyl-[1,2]dioxetane 
• 94-30-4 ethyl 4-methoxybenzoate 
• 74-95-3 1,1-dibromomethane 
• 119205-35-5 4-methoxy-α-bromoacetophenone methyl hemiacetal 
• 36881-00-2 2-(4-methoxyphenyl)-2-methyI-1,3-dioxolane 
• 67-56-1 methanol 
• 33675-41-1 1-bromo-2-(4-methoxyphenyl)acetylene 
• 64-19-7 acetic acid 
• 128-08-5 N-Bromosuccinimide 
• 186581-53-3 diazomethane 
• 100-07-2 4-methoxy-benzoyl chloride 

Downstream Products

• 80354-61-6 1-(4-methoxy-phenyl)-2-piperidino-ethanone 
• 39954-65-9 1-(4'-methoxyphenacyl)quinolinium bromide 
• 35512-31-3 4-(4-methoxyphenyl)-1H-imidazole 
• 855606-02-9 (6-benzyloxy-3-methyl-benzofuran-2-yl)-(4-methoxy-phenyl)-ketone 
• 101723-50-6 (3,5-dimethyl-benzofuran-2-yl)-(4-methoxy-phenyl)-ketone 
• 101446-67-7 (5-chloro-3-methyl-benzofuran-2-yl)-(4-methoxy-phenyl)-ketone 
• 46332-91-6 (4-methoxy-phenyl)-glyoxylohydroximoyl bromide 
• 102018-70-2 (3-ethyl-5-methyl-benzofuran-2-yl)-(4-methoxy-phenyl)-ketone 
• 860741-50-0 1-(4-methoxy-phenyl)-2-(3,4,5-trimethoxy-phenoxy)-ethanone 
• 101446-28-0 (5-bromo-3-methyl-benzofuran-2-yl)-(4-methoxy-phenyl)-ketone 
• 108720-90-7 (3-ethyl-5-bromo-benzofuran-2-yl)-(4-methoxy-phenyl)-ketone 
• 79965-74-5 4-(4-methoxyphenyl)-2-methyloxazole 
• 58518-78-8 p-methoxyphenacyl acetate 
• 29917-69-9 1-(p-methoxyphenyl)-3-phenylpropan-2-one 

Relevant articles and documents

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Novel hybrid conjugates with dual estrogen receptor α degradation and histone deacetylase inhibitory activities for breast cancer therapy

Hormone therapy targeting estrogen receptors is widely used clinically for the treatment of breast cancer, such as tamoxifen, but most of them are partial agonists, which can cause serious side effects after long-term use. The use of selective estrogen receptor down-regulators (SERDs) may be an effective alternative to breast cancer therapy by directly degrading ERα protein to shut down ERα signaling. However, the solely clinically used SERD fulvestrant, is low orally bioavailable and requires intravenous injection, which severely limits its clinical application. On the other hand, double- or multi-target conjugates, which are able to synergize antitumor activity by different pathways, thus may enhance therapeutic effect in comparison with single targeted therapy. In this study, we designed and synthesized a series of novel dual-functional conjugates targeting both ERα degradation and histone deacetylase inhibiton by combining a privileged SERD skeleton 7-oxabicyclo[2.2.1]heptane sulfonamide (OBHSA) with a histone deacetylase inhibitor side chain. We found that substituents on both the sulfonamide nitrogen and phenyl group of OBHSA unit had significant effect on biological activities. Among them, conjugate 16i with N-methyl and naphthyl groups exhibited potent antiproliferative activity against MCF-7 cells, and excellent ERα degradation activity and HDACs inhibitory ability. A further molecular docking study indicated the interaction patterns of these conjugates with ERα, which may provide guidance to design novel SERDs or PROTAC-like SERDs for breast cancer therapy.

First synthesis of tabamides A–C and their derivatives: In vitro nitric oxide inhibitory activity

The first synthesis of natural phenolic amides, tabamides A–C (1–3), and their derivatives (4–12) was accomplished using Stobbe condensation and amide coupling reactions as key steps. The in vitro nitric oxide (NO) inhibitory effects of these compounds in LPS-induced RAW-264.7 macrophages were evaluated as an indicator of anti-inflammatory activity. All compounds tested had a concentration-dependent inhibitory effect on NO production by RAW-264.7 macrophages without significant cytotoxicity. Compound 6, a tabamide A derivative (IC50 = 82.6 μM), followed by tabamide A (1, IC50 = 100.7 μM), was the most potent from the series. The present study revealed that tabamide A (1) could be considered as a lead structure to develop NO production-targeted anti-inflammatory agents.