3430-22-6

Basic information

• Product Name: 3-Bromo-4-methylpyridine
• Synonyms: 4-METHYL-3-BROMOPYRIDINE;3-BROMO-4-PICOLINE;3-BROMO-4-METHYLPYRIDINE;3-BROMO-4-METHYLPYRIDINE 98%;3-BROMO-4-METHYLPYRIDINE 99+%;Bromomethylpyridine;3-BROMO-4-METHYLPYRIDINE (3-BROMO-4-PICOLINE);4-Methyl-3-bromopyridine 3-Bromo-4-picoline
• CAS NO: 3430-22-6
• Molecular Formula: C₆H₆BrN
• Molecular Weight: 172.02
• EINECS: 1592732-453-0
• Product Categories: blocks;Bromides;Pyridines;Pyridine;Pyridines, Pyrimidines, Purines and Pteredines;Halides;Pyridines derivates;Aromatics Compounds;Bromopyridines;Halopyridines;Aromatics;C6Heterocyclic Building Blocks;Halogenated Heterocycles;Heterocyclic Building Blocks;Brominated heterocyclic series;Pyridine Series;Heterocycles;Heterocycle-Pyridine series;alkyl bromide
• Mol File: 3430-22-6.mol

Chemical Properties

• Boiling Point: 199-200 °C(lit.)
• Flash Point: 175 °F
• Appearance: Clear colorless to yellow/Liquid
• Density: 1.549 g/mL at 25 °C(lit.)
• Refractive Index: n20/D 1.56(lit.)
• Storage Temp.: Inert atmosphere,Room Temperature
• Solubility: Chloroform, Methanol
• PKA: 3.54±0.18(Predicted)
• BRN: 878354
• CAS DataBase Reference: 3-Bromo-4-methylpyridine(CAS DataBase Reference)
• NIST Chemistry Reference: 3-Bromo-4-methylpyridine(3430-22-6)
• EPA Substance Registry System: 3-Bromo-4-methylpyridine(3430-22-6)

Safety Data

• Hazard Codes: Xi,Xn
• Statements: 36/37/38-20/21/22
• Safety Statements: 26-36-2636
• RIDADR: Cool, dry,tightly closed
• WGK Germany: 3
• HazardClass: IRRITANT
• PackingGroup: III
• Hazardous Substances Data: 3430-22-6(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
3-Bromo-4-methylpyridine is used as an intermediate for the synthesis of pyridinyl pyrrole compounds, which act as proton pump inhibitors. These compounds have improved gastric acid secretion suppressive activity, making them valuable in the treatment of conditions related to excessive stomach acid.
Used in the Synthesis of PDE4 Inhibitors:
3-Bromo-4-methylpyridine is used as a building block in the preparation of substituted 4-(2,2-diphenylethyl)pyridine-N-oxides. These compounds serve as potent phosphodiesterase type 4 (PDE4) inhibitors, which have potential applications in the treatment of various inflammatory and autoimmune diseases.
Used in the Synthesis of Benzodiazepine Site Ligands:
3-Bromo-4-methylpyridine is also utilized in the synthesis of benzodiazepine site ligands bearing a tricyclic pyridone moiety for human GABAA receptors. These ligands have potential applications in the treatment of anxiety, insomnia, and other conditions related to the GABAergic system.
Used in the Synthesis of Ascididemin Isomers:
3-Bromo-4-methylpyridine is employed in the synthesis of a novel isomer of ascididemin, a potent anticancer agent. This isomer may exhibit improved pharmacological properties and enhanced efficacy against various types of cancer.
Used in the Synthesis of 3-Bromo-4-Carbonitrile:
Additionally, 3-Bromo-4-methylpyridine is used in the preparation of 3-bromopyridine-4-carbonitrile, which can be further utilized in the synthesis of various pharmaceutical compounds with potential therapeutic applications.

Synthetic route

3-amino-4-methylpyridine (3430-27-1) → 3-Bromo-4-methylpyridin (3430-22-6)

Conditions	Yield
Stage #1: 3-amino-4-methylpyridine With hydrogen bromide; bromine at -5℃; Stage #2: With sodium nitrite In water at 0℃; Stage #3: With sodium hydroxide In water at 0 - 20℃; for 0.5h; pH=9;	95%
Stage #1: 3-amino-4-methylpyridine With hydrogen bromide; bromine at -5℃; Stage #2: With sodium nitrite at 0℃; Stage #3: With sodium hydroxide at 20℃; for 0.5h; pH=9;

picoline (108-89-4) → 3-Bromo-4-methylpyridin (3430-22-6)

Conditions	Yield
Stage #1: picoline With aluminum (III) chloride; potassium bromide at 20℃; for 1h; Inert atmosphere; Stage #2: With bromine at 120℃; for 27h; Inert atmosphere;	57%
With aluminum (III) chloride; bromine at 95 - 105℃; for 43h; Inert atmosphere;	49%
Stage #1: picoline With aluminum (III) chloride; bromine at 95 - 100℃; for 22h; Stage #2: With sodium carbonate In water	19%
With hydrogenchloride; sodium hydroxide; bromine; aluminium trichloride In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; dichloromethane; Petroleum ether
Stage #1: picoline With aluminum (III) chloride at -5℃; for 1h; Stage #2: With bromine at 100℃; for 44h;

3-Bromopyridine (626-55-1) + lithium diisopropyl amide (4111-54-0) + methyl iodide (74-88-4) → 4-bromopyridin (1120-87-2) + 4-bromo-3-methylpyridine (10168-00-0) + 3-Bromo-4-methylpyridin (3430-22-6)

Conditions	Yield
In tetrahydrofuran at -60℃; Product distribution; Mechanism; temp. change;

3-Bromopyridine (626-55-1) + methyl iodide (74-88-4) → 4-bromo-3-methylpyridine (10168-00-0) + 3-Bromo-4-methylpyridin (3430-22-6)

Conditions	Yield
THF, -60 -> -55.deg C, 1) 15 min, 2) 45 min; Yield given. Multistep reaction. Yields of byproduct given;

3-Bromopyridine (626-55-1) + methyl iodide (74-88-4) → 3-Bromo-4-methylpyridin (3430-22-6)

Conditions	Yield
THF, -60.deg C, 1) 15 min, 2) 45 min; Yield given. Multistep reaction;

3-Bromo-4-methyl-4H-pyridine-1-carboxylic acid phenyl ester (90731-85-4) → 3-Bromo-4-methylpyridin (3430-22-6)

Conditions	Yield
With o-tetrachloroquinone In acetic acid for 8h; Ambient temperature; Yield given;

3-Bromopyridine (626-55-1) → 3-Bromo-4-methylpyridin (3430-22-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) CuI, (CH3)2S / 1.) THF, -20 deg C, 5 min, 2.) THF, a) -20 deg C, 15 min, b) RT, 15 min 2: o-chloranil / acetic acid / 8 h / Ambient temperature View Scheme

3-Bromo-4-methylpyridin (3430-22-6) + 2,4-dimethoxypyrimidin-5-ylboronic acid (89641-18-9) → 5-(4-methyl-pyridin-3-yl)-2,4-dimethoxy-pyrimidine (952403-13-3)

Conditions	Yield
With sodium carbonate; palladium diacetate; triphenylphosphine In propan-1-ol for 3h; Suzuki Coupling; Heating / reflux;	100%

3-Bromo-4-methylpyridin (3430-22-6) + Diethyl carbonate (105-58-8) → ethyl 2-(3-bromopyridin-4-yl)acetate (51054-99-0)

Conditions	Yield
Stage #1: 3-Bromo-4-methylpyridin With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 2.5h; Stage #2: Diethyl carbonate In tetrahydrofuran for 12h;	100%
Stage #1: 3-Bromo-4-methylpyridin; Diethyl carbonate With lithium hexamethyldisilazane In tetrahydrofuran at 0℃; for 5h; Stage #2: With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 2h;	91%
With lithium hexamethyldisilazane In tetrahydrofuran at 0℃; for 3h; Inert atmosphere;	68.2%
Stage #1: 3-Bromo-4-methylpyridin With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; Stage #2: Diethyl carbonate In tetrahydrofuran at 20℃;	63%

2-formyl-4,5-(methylenedioxy)benzeneboronic acid (94838-88-7) + 3-Bromo-4-methylpyridin (3430-22-6) → 6-(4-methyl-pyridin-3-yl)-benzo[1,3]dioxole-5-carbaldehyde (1086561-33-2)

Conditions	Yield
With sodium carbonate; tetrakis(triphenylphosphine) palladium(0) In methanol; water; toluene at 90℃; for 15h; Suzuki coupling;	98%

benzo[b]thiophene-2-boronic acid (98437-23-1) + 3-Bromo-4-methylpyridin (3430-22-6) → 3-(benzo[b]thiophen-2-yl)-4-methylpyridine (1443643-88-6)

Conditions	Yield
With C43H37ClFeNiP2*C4H8O; potassium carbonate In tetrahydrofuran; acetonitrile at 50℃; for 12h; Suzuki-Miyaura Coupling; Inert atmosphere;	97%

thiophene boronic acid (6165-68-0) + 3-Bromo-4-methylpyridin (3430-22-6) → 4-methyl-3-(thiophen-2-yl)pyridine (504395-36-2)

Conditions	Yield
With potassium phosphate; C43H37ClFeNiP2*C4H8O In 1,4-dioxane at 70℃; for 8h; Suzuki-Miyaura Coupling; Inert atmosphere;	97%

4-acetylphenylboronic acid (149104-90-5) + 3-Bromo-4-methylpyridin (3430-22-6) → 1-(4-(4-methylpyridin-3-yl)phenyl)ethan-1-one

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In water; toluene at 120℃; for 10h; Suzuki Coupling;	97%

carbonic acid dimethyl ester (616-38-6) + 3-Bromo-4-methylpyridin (3430-22-6) + methyl iodide (74-88-4) → methyl 2-(3-bromopyridin-4-yl)propanoate

Conditions	Yield
Stage #1: 3-Bromo-4-methylpyridin With lithium hexamethyldisilazane In tetrahydrofuran; ethylbenzene at 20℃; for 3h; Stage #2: carbonic acid dimethyl ester In tetrahydrofuran; ethylbenzene at 0 - 20℃; Stage #3: methyl iodide In tetrahydrofuran; ethylbenzene at -70 - 20℃;	97%

carbonic acid dimethyl ester (616-38-6) + 3-Bromo-4-methylpyridin (3430-22-6) → methyl 2-(3-bromopyridin-4-yl)acetate (162615-12-5)

Conditions	Yield
Stage #1: 3-Bromo-4-methylpyridin With lithium hexamethyldisilazane In tetrahydrofuran for 1.5h; Stage #2: carbonic acid dimethyl ester In tetrahydrofuran for 15h;	96%
Stage #1: 3-Bromo-4-methylpyridin With lithium hexamethyldisilazane In tetrahydrofuran; ethylbenzene at 20℃; for 3h; Stage #2: carbonic acid dimethyl ester In tetrahydrofuran; ethylbenzene at 0 - 20℃;	95%
With lithium hexamethyldisilazane In tetrahydrofuran at 0 - 20℃; for 2.5h;	85%
With n-butyllithium; diisopropylamine 1.) THF, hexane, r.t. to 50 deg C, 2.) THF, hexane, 50 deg C; r.t., 24 h; Yield given. Multistep reaction;

2-formylbenzene boronic acid (40138-16-7) + 3-Bromo-4-methylpyridin (3430-22-6) → 2-(4-methyl-pyridin-3-yl)-benzaldehyde (1086561-21-8)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In methanol; water; toluene at 90℃; for 15h; Inert atmosphere;	96%
With sodium carbonate; tetrakis(triphenylphosphine) palladium(0) In methanol; water; toluene at 90℃; for 15h; Suzuki coupling;	94%
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In tetrahydrofuran; water at 70℃; for 12h; Suzuki Coupling;	85%

methylamine (74-89-5) + 3-Bromo-4-methylpyridin (3430-22-6) → 4-Methyl-3-(methylamino)pyridine (77862-24-9)

Conditions	Yield
With copper In water at 150 - 160℃; Temperature; Reagent/catalyst;	95%
With copper In water at 100 - 110℃; for 24h; Temperature; Autoclave;	93%
With copper(II) sulfate	68%

Methyl formate (107-31-3) + 3-Bromo-4-methylpyridin (3430-22-6) → 4-methylnicotinaldehyde (51227-28-2)

Conditions	Yield
Stage #1: 3-Bromo-4-methylpyridin With n-butyllithium In tetrahydrofuran at -100℃; for 0.166667h; Stage #2: Methyl formate In tetrahydrofuran at -96 - -78℃; for 1h;	95%

3-[4-methoxymethyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-yl]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridine (916326-87-9) + 3-Bromo-4-methylpyridin (3430-22-6) → 3-[4-methoxymethyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-yl]-5-(4-methyl-pyridin-3-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridine (916326-94-8)

Conditions	Yield
With sodium carbonate; tetrakis(triphenylphosphine) palladium(0) In 1,4-dioxane; water at 90℃;	95%

N-boc-2-pyrroleboronic acid (135884-31-0) + 3-Bromo-4-methylpyridin (3430-22-6) → tert-butyl 2-(4-methylpyridin-3-yl)-1H-pyrrole-1-carboxylate (1443644-02-7)

Conditions	Yield
With potassium phosphate; C43H37ClFeNiP2*C4H8O In 1,4-dioxane at 70℃; for 8h; Suzuki-Miyaura Coupling; Inert atmosphere;	95%

3-Bromo-4-methylpyridin (3430-22-6) → 3-amino-4-methylpyridine (3430-27-1)

Conditions	Yield
With ammonia; copper(II) sulfate In methanol at 160℃; under 3800.26 Torr; for 8h; Temperature; Autoclave;	95%
With ammonium hydroxide; L-2-O-methyl-chiro-inositol; copper(II) acetate monohydrate In 1-methyl-pyrrolidin-2-one at 110℃; for 30h;	80%

3-Bromo-4-methylpyridin (3430-22-6) → 3-iodo-4-methyl-pyridine (38749-96-1)

Conditions	Yield
With copper(l) iodide; N,N-dimethylethylenediamine; sodium iodide In 1,4-dioxane at 110℃; for 72h; Inert atmosphere;	95%

tert-Butoxybis(dimethylamino)methane (5815-08-7) + 3-Bromo-4-methylpyridin (3430-22-6) → (E)-2-(3-bromopyridin-4-yl)-N,N-dimethylethen-1-amine

Conditions	Yield
In N,N-dimethyl-formamide at 135℃; for 5h;	95%

3-bromo-1-(trimethylsilyl)-1-propyne (38002-45-8) + 3-Bromo-4-methylpyridin (3430-22-6) → 3-bromo-4-[4-(trimethylsilyl)but-3-yn-1-yl]pyridine (1035428-67-1)

Conditions	Yield
Stage #1: 3-Bromo-4-methylpyridin With lithium diisopropyl amide In tetrahydrofuran; hexane at 50℃; for 0.75h; Stage #2: 3-bromo-1-(trimethylsilyl)-1-propyne In tetrahydrofuran; hexane at 0 - 20℃; Further stages.;	93%

sodium carbonate (497-19-8) + 3-Bromo-4-methylpyridin (3430-22-6) + formic acid ethyl ester (109-94-4) → 4-methylnicotinaldehyde (51227-28-2)

Conditions	Yield
With hydrogenchloride; n-butyllithium In tetrahydrofuran; hexane; water	93%

3-Bromo-4-methylpyridin (3430-22-6) → 3-bromo-4-methyl-1-oxidopyridin-1-ium (17117-15-6)

Conditions	Yield
With dihydrogen peroxide; methyltrioxorhenium(VII) In dichloromethane; water at 20℃;	93%
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 2h;

3-Bromo-4-methylpyridin (3430-22-6) + formic acid ethyl ester (109-94-4) → 4-methylnicotinaldehyde (51227-28-2)

Conditions	Yield
Stage #1: 3-Bromo-4-methylpyridin With n-butyllithium In tetrahydrofuran; hexane at -100 - 100℃; for 0.166667h; Stage #2: formic acid ethyl ester In tetrahydrofuran; hexane at 100℃; for 0.5h;	93%

allyl bromide (106-95-6) + 3-Bromo-4-methylpyridin (3430-22-6) → 3-bromo-4-(but-3-en-1-yl)pyridine (1309650-03-0)

Conditions	Yield
Stage #1: 3-Bromo-4-methylpyridin With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.833333h; Stage #2: allyl bromide In tetrahydrofuran at -78 - 20℃;	92%

phenylacetylene (536-74-3) + 3-Bromo-4-methylpyridin (3430-22-6) → 3-(phenylethynyl)-4-methylpyridine (63731-34-0)

Conditions	Yield
Stage #1: 3-Bromo-4-methylpyridin With bis(η3-allyl-μ-chloropalladium(II)); 1-n-butyl-3-methylimidazolium tetrafluoroborate; triphenylphosphine at 60℃; Heck alkynylation; Inert atmosphere; Stage #2: phenylacetylene With pyrrolidine at 100℃; for 4h; Heck alkynylation; Inert atmosphere;	92%
With tetrabutylammomium bromide; sodium acetate In dimethyl sulfoxide at 120℃; for 50h; Sonogashira Cross-Coupling; Inert atmosphere;	69%

benzofuran-2-boronic acid (98437-24-2) + 3-Bromo-4-methylpyridin (3430-22-6) → 3-(benzofuran-2-yl)-4-methylpyridine (1269386-42-6)

Conditions	Yield
With C43H37ClFeNiP2*C4H8O; potassium carbonate In tetrahydrofuran; acetonitrile at 50℃; for 12h; Suzuki-Miyaura Coupling; Inert atmosphere;	92%

tributyl(1-ethoxyvinyl)stannane (97674-02-7) + 3-Bromo-4-methylpyridin (3430-22-6) → 3-(1-Ethoxy-vinyl)-4-methyl-pyridine (486414-68-0)

Conditions	Yield
tetrakis(triphenylphosphine) palladium(0) In toluene for 4h; Heating / reflux;	91%

benzophenone hydrazone (5350-57-2) + 3-Bromo-4-methylpyridin (3430-22-6) → diphenylmethanone (4-methylpyridin-3-yl)hydrazone (928263-96-1)

Conditions	Yield
With sodium t-butanolate; palladium diacetate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In toluene at 85℃;	91%

cobalt(II) chloride hexahydrate + 6-Bromo-1-hexene (2695-47-8) + butane-2,3-dione dioxime (95-45-4) + 3-Bromo-4-methylpyridin (3430-22-6) → (3-bromo-4-methylpyridine)bis(dimethylglyoximato)-5-hexenylcobalt(III)

Conditions	Yield
With sodium hydroxide; sodium tetrahydroborate In methanol stirring CoCl2, glyoxime in CH3OH at -20°C under N2; addn. of 50% aq. NaOH soln., 3-bromo-4-methylpyridine, NaBH4 in CH3OH; stirring at 20°C for 1 h; addn. of bromide at -20, stirring at 20°C in dark for 14 h;; addn. of water containing 1 drop 3-bromo-4-methylpyridine to oily residue; pptn.; drying; elem. anal.;	91%

(9-fluoro-1-methyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)boronic acid (1464115-37-4) + 3-Bromo-4-methylpyridin (3430-22-6) → 9-fluoro-1-methyl-7-(4-methyl-pyridin-3-yl)-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline (1404366-47-7)

Conditions	Yield
With tetrabutylammomium bromide; palladium diacetate; sodium carbonate In ethanol; water; toluene Suzuki Coupling; Inert atmosphere; Reflux;	91%

3-Bromo-4-methylpyridin (3430-22-6) → 3-bromoisonicotinic acid (13959-02-9)

Conditions	Yield
Stage #1: 3-Bromo-4-methylpyridin With Co0.27CuO3; water Stage #2: With oxygen at 90℃;	90%
With potassium permanganate In water Heating / reflux;	32%
With hydrogenchloride; potassium permanganate In water

(5-(((tert-butoxycarbonyl)amino)methyl)furan-2-yl)boronic acid (1072946-49-6) + 3-Bromo-4-methylpyridin (3430-22-6) → tert-butyl ((5-(4-methylpyridin-3-yl)furan-2-yl)methyl)carbamate

Conditions	Yield
With trans-bis(triphenylphosphine)palladium dichloride; sodium carbonate In 1,2-dimethoxyethane; ethanol; water at 140℃; for 0.0333333h; Suzuki Coupling; Inert atmosphere; Microwave irradiation;	89.4%
With trans-bis(triphenylphosphine)palladium dichloride; sodium carbonate In 1,2-dimethoxyethane; ethanol; water at 140℃; for 0.0333333h; Microwave irradiation; Inert atmosphere;	89%

Upstream product

• 108-89-4 picoline 
• 3430-27-1 3-amino-4-methylpyridine 
• 626-55-1 3-Bromopyridine 
• 90731-85-4 3-Bromo-4-methyl-4H-pyridine-1-carboxylic acid phenyl ester 
• 74-88-4 methyl iodide 
• 4111-54-0 lithium diisopropyl amide 

Downstream Products

• 162615-12-5 methyl 2-(3-bromopyridin-4-yl)acetate 
• 229184-01-4 3-bromo-4-[3-hydroxypropyl]pyridine 
• 868993-32-2 N,N-diethyl-4 fluoro-2-(4-methylpyridin-3-yl)benzamide 
• 1086561-21-8 2-(4-methyl-pyridin-3-yl)-benzaldehyde 
• 1187367-25-4 N-{3-(6-methyl-pyridin-3-yl)-1-[4-(4-methyl-pyridin-3-yl)-phenyl]-4,5-dihydro-1H-pyrazolo[4,3-g]benzothiazol-7-yl}-acetamide 
• 1210868-03-3 3-(benzylsulfanyl)-4-methylpyridine 
• 1240286-89-8 tert-butyl {4-chloro-2-[(4-methylpyridin-3-yl)ethynyl]phenoxy}acetate 
• 18631-22-6 5H-indeno[1,2-c]pyridin-5-one 
• 3882-46-0 5H-indeno[1,2-b]pyridin-5-one 
• 1345121-33-6 N-[5-(5-methyl(8-hydropyrazolo[1,5-a]pyridin-4-yl))(2-pyridyl)](2,6-difluorophenyl)carboxamide 
• 1345121-27-8 N-[5-(5-methyl-(8-hydropyrazolo[1,5-a]pyridin-6-yl))(2-pyridyl)](2,6-difluorophenyl)carboxamide 
• 1345121-29-0 4-bromo-5-methyl-pyrazolo[1,5-a]pyridine 
• 1345121-23-4 6-bromo-5-methyl-8-hydropyrazolo[1,5-a]pyridine 
• 1345121-21-2 methyl 4-bromo-5-methyl-8-hydropyrazolo[1,5-a]pyridine-3-carboxylate 

Relevant articles and documents

Preparation method of (S)-4- (C)-3-(S)-bromopyridine (bromopyridine) (by machine translation)

The method disclosed by the invention has, the beneficial, effects :(1) that 4 - the reaction conditions are mild, the treatment is easy 4 - the method is easy to, operate, the, treatment, is easy . and the method is, easy to, operate 4 - and easy to ;(2) operate 4 - pH, 4 . (by machine translation)

Method for synthesizing 3-bromoisonicotinic acid intermediate

The invention relates to a method for synthesizing a 3-bromoisonicotinic acid intermediate, and belongs to the technical field of pharmaceutical intermediates. The process comprises the following steps: 4-methylpyridine is adopted as a raw material, and the 4-methylpyridine is reacted with bromine under the catalysis of an aluminum trichloride catalyst to form intermediate 3-bromo-4-methylpyridine; and a novel catalyst Co0.27CuO3 is added, oxygen is introduced for oxidization to form the target product 3-bromoisonicotinic acid. According to the method provided by the invention, in the oxidation reaction process, water is used as a solvent, the novel catalyst Co0.27CuO3 is introduced, the oxygen is used as an oxidant to replace a traditional KMnO4 oxidant, so that pollution of heavy metalsto the environment can be avoided; because the novel catalyst is not affected by the reaction environment, catalytic activity of the novel catalyst is not reduced, and after 25 cycles, activity of thecatalyst is not significantly reduced; and the method has the advantages of greatly improving the yield, reducing the costs, improving the safety, saving the energy, and the like, and conforms to modern chemical industry production requirements of a green reaction.

A 4 - methyl -3 - bromo pyridine preparation method

The invention belongs to the field of organic synthesis, in particular to a 4 - methyl - 3 - bromo pyridine method, comprises the following steps: (1) to 4 - methyl - 3 - nitro pyridine as raw materials, methanol as solvent, under the effects of catalyst hydrogenation reduction, filtered, the filtrate is concentrated, be 4 - methyl - 3 - aminopyridine; (2) the 4 - methyl - 3 - aminopyridine reacts with acid to form the salt cooling to - 10 °C - 0 °C, [...], [...] sodium nitrite aqueous solution, pH adjusting solution is dropped is alkaline, and then extracted, drying, concentration, a 4 - methyl - 3 - bromo pyridine. The beneficial effect of the invention is: mild reaction conditions, is easy to operate, after treatment is simple, and easy to enlarge production, is extremely suitable for industrial production; good catalytic effect, high yield; low prices of raw materials, the production cost is low.

Preparation method for nevirapine intermediate

The invention relates to a preparation method for an intermediate, i.e., 2-chloro-3-amino-4-methylpyridine, of an anti-AIDs drug nevirapine. The intermediate has a chemical structural formula I as described in the specification. The preparation method is characterized in that 4-methylpyridine is subjected to halogenation, ammonia substitution and chlorination so as to prepare 2-chloro-3-amino-4-methylpyridine. The preparation reactions are as shown in the specifications, wherein X is bromine or chlorine; a halogenation condition is Br2/AlCl3/95-105 DEG C, Br2/AlCl3/MBr/110 to 130 DEG C (wherein M is Li, Na or K), Br2/Fe/135-145 DEG C, Cl2/AlCl3, Br2/FeCl3 or Br2/SnCl4; an ammonia substitution condition is NH3(g)/CuSO4/CH3OH/170-190 DEG C, NH3(aq)/CuSO4/170-190 DEG C, or NaNH2; and a chlorination reaction condition is Cl2/AlCl3 or HCl/H2O2/30-50 DEG C.

PROCESS FOR THE PREPARATION OF TOFACITINIB AND INTERMEDIATES THEREOF

The present invention provides compounds of Formula III and Formula VI, and processes for their preparation. The present invention further provides use of the compounds of Formula III and Formula VI for the preparation of tofacitinib or isomers or a mixture of isomers or salts thereof.

Novel 3beta-amino azabicyclooctane heteroaromatic amid derivatives preparation method and therapeutic uses thereof

The invention concerns compounds of general formula 1, wherein: A, B, D and E represent one or two nitrogen atoms, the others being carbon atoms; X represents a S or, a O, thereby forming a bicyclic fused heteroaromatic, such as thieno[2,3-b]pyridine, furo[2,3-b]pyridine, thieno[3,2-b]pyridine, furo[3,2-b]pyridine, thieno[2,3-b]pyrazine, furo[2,3-b]pyrazine, thieno[2,3-c]pyridine, furo[2,3-c]pyridine, thieno[3,2-c]pyridine and furo[3,2-c]pyridine; R1 represents a linear or branched C1-C6 alkoxy group, a linear or branched C1-C6 alkylthio group; R2 represents a linear, branched, cyclic C2-C8 group, a 2- or 3- thienylmethyl group, or a benzyl group optionally substituted by one or several halogens, F, Cl, Br, I, C1-C4 alkyl, C1-C4 alkoxy, CF3, CN, NO2, OH; and their pharmaceutically acceptable salts. Said compounds are anti-dopaminergic agents.

2-(aza-9-fluorenonyl)carbapenem antibacterial agents

Carbapenems of the formula STR1 wherein a suitably substituted aza-9-fluorenone is attached at the 2-position of the carbapenem are useful antibacterial agents.

SYNTHESIS OF 3-HALO- AND 3-FORMYL-4-ALKYLPYRIDINES

In the presence of a catalytic amount of cuprous iodide, the addition of Grignard reagents to the 1-phenoxycarbonyl salts of 3-halopyridines gives 4-alkyl-3-halo-1-phenoxycarbonyl-1,4-dihydropyridines.The crude dihydropyridines were aromatized with o-chloroanil to give 4-alkyl-3-halopyridines.Several 4-alkylnicotinaldehydes were synthesized in a similar manner from the cyclic acetal (1,3-dioxolane) of 3-pyridinecarboxaldehyde.After aromatization with sulfur, the crude acetals were hydrolyzed with oxalic acid to give the desired pyridinecarboxaldehydes.

REACTION DE LA BROMO-3 PYRIDINE AVEC LE DIISOPROPYLAMIDURE DE LITHIUM. MECANISMES DE METALLATION ET DE MIGRATION D'HALOGENE. REGIOSELECTIVITE DE L'ADDITION POLAIRE SUR LA PYRIDYNE-3,4

3-bromo pyridine behaviour towards lithium diisopropyl amide (LDA) in THF is studied.A careful study of the experimental conditions point to a metallation reaction in a position 4 and a "halogen dance" mechanism with isomerisation into a 4-bromo pyridine.Conversion into diisopropylamino compounds occurs simultaneously with a 3 oriented elimination-addition (EA) reaction from transient isomeric lithio-derivatives and a competing addition-elimination (AE) mechanism from the in situ formed 4-bromo pyridine.