22889-78-7

Basic information

• Product Name: 4-Amino-3,5-dichloropyridine
• Synonyms: 4-AMINO-3,5-DICHLOROPYRIDINE, 98+%;4-Amino-3,5-Dichloropyridine 99%;4-Amino-3,5-dichloropyridin-4-amine;4- aMino-3,5- twochlorine pyridine;AMino - 4-3, 5 - dichloro pyridine;4-Amino-3,5-dichloropyridine 3,5-Dichloro-4-pyridinamine;Roflumilast Imp.C;AURORA 23319
• CAS NO: 22889-78-7
• Molecular Formula: C₅H₄Cl₂N₂
• Molecular Weight: 163
• EINECS: 245-304-6
• Product Categories: pharmacetical;Amines;Pyridines;Chloropyridines;Halopyridines;Boronic Acid;Roflumilast interemdiate;Pyridine;Pyridines, Pyrimidines, Purines and Pteredines
• Mol File: 22889-78-7.mol

Chemical Properties

• Melting Point: 159°C
• Boiling Point: 250.8 °C at 760 mmHg
• Flash Point: 105.5 °C
• Appearance: /
• Density: 1.497 g/cm³
• Vapor Pressure: 0.0212mmHg at 25°C
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• Solubility: Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)
• PKA: 1.48±0.10(Predicted)
• BRN: 120547
• CAS DataBase Reference: 4-Amino-3,5-dichloropyridine(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Amino-3,5-dichloropyridine(22889-78-7)
• EPA Substance Registry System: 4-Amino-3,5-dichloropyridine(22889-78-7)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• HazardClass: IRRITANT
• Hazardous Substances Data: 22889-78-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
4-Amino-3,5-dichloropyridine is used as an intermediate compound for the development of PDE4 inhibitors, specifically for Roflumilast. It plays a crucial role in modulating the activity of phosphodiesterase enzymes, which are involved in various cellular processes, including inflammation and immune response. By targeting PDE4, this compound contributes to the therapeutic effects of Roflumilast, which is used to treat chronic obstructive pulmonary disease (COPD) and other inflammatory conditions.
Additionally, due to its chemical properties as a crystalline powder, 4-Amino-3,5-dichloropyridine may also be utilized in the synthesis of other pharmaceutical compounds or as a research tool in the study of PDE4 inhibitors and their mechanisms of action.

InChI:InChI=1/C5H4Cl2N2/c6-3-1-9-2-4(7)5(3)8/h1-2H,(H2,8,9)/p+1

Synthetic route

4-aminopyridine (504-24-5) → 3,5-dichloro-4-aminopyridine (22889-78-7)

Conditions	Yield
Stage #1: 4-aminopyridine With hydrogenchloride; dihydrogen peroxide In water at 10 - 72℃; for 3.25h; Stage #2: With sodium hydroxide In water at 45℃; for 0.5h; pH=9 - 10; Reagent/catalyst; Temperature;	92.7%
With hydrogenchloride; dihydrogen peroxide
With aqueous hydrogen peroxide In concentrated hydrochloric acid

3,3,5,5-tetrachloropiperidin-4-one → 3,5-dichloro-4-aminopyridine (22889-78-7)

Conditions	Yield
With ammonia In methanol at 40 - 45℃; for 4h; Autoclave;	89.7%

3,5-dichloropyridine-4-carbonitrile (153463-65-1) → 3,5-dichloro-4-aminopyridine (22889-78-7)

Conditions	Yield
With lithium amide In ammonia 0 deg C to RT;	54%

4-amino-3-chloropyridine (19798-77-7) → 3,5-dichloro-4-aminopyridine (22889-78-7)

Conditions	Yield
With hydrogenchloride; dihydrogen peroxide

3,4,5-trichloropyridine (33216-52-3) → 3,5-dichloro-4-aminopyridine (22889-78-7)

Conditions	Yield
With ammonium hydroxide at 150℃; im Rohr;

4-amino-3,5-dichloro-pyridine-2-carboxylic acid (17122-17-7) → 3,5-dichloro-4-aminopyridine (22889-78-7)

Conditions	Yield
Erhitzen ueber den Schmelzpunkt;

3.5-dichloro-4-amino-picolinic acid → 3,5-dichloro-4-aminopyridine (22889-78-7)

Conditions	Yield
beim Erhitzen ueber den Schmelzpunkt;

3,4,5-trichloropyridine (33216-52-3) + ammonia (7664-41-7) → 3,5-dichloro-4-aminopyridine (22889-78-7)

Conditions	Yield
at 150℃; im Rohr;

4-aminopyridine (504-24-5) + hydrogenchloride (7647-01-0) + water (7732-18-5) + dihydrogen peroxide (7722-84-1) → 3,5-dichloro-4-aminopyridine (22889-78-7)

hydrogenchloride (7647-01-0) + 4-(nitroamino)pyridine (26482-55-3) → 4-Chloropyridine (626-61-9) + 3,4,5-trichloropyridine (33216-52-3) + 3,5-dichloro-4-aminopyridine (22889-78-7)

Conditions	Yield
at 100℃;

3-amino-4-chloropyridine (20511-15-3) → 3,5-dichloro-4-aminopyridine (22889-78-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium nitrite; copper-powder; aqueous hydrochloric acid / Diazotization 2: aqueous NH3 / 190 °C 3: concentrated aqueous HCl; aqueous H2O2 View Scheme

3,4-dichloropyridine (55934-00-4) → 3,5-dichloro-4-aminopyridine (22889-78-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: aqueous NH3 / 190 °C 2: concentrated aqueous HCl; aqueous H2O2 View Scheme

3-benzoyloxy-4-methoxybenzoyl chloride (144036-22-6) → 3,5-dichloro-4-aminopyridine (22889-78-7) + N-(3,5-dichloropyrid-4-yl)-3-benzoyloxy-4-methoxybenzamide (159782-90-8)

3,5-dichloro-4-aminopyridine (22889-78-7) → 5-[5-{[(3,5-dichloropyridin-4-yl)amino]carbonyl}-2-(difluoromethoxy) phenoxy]pentanoic acid (1422361-76-9)

Conditions	Yield
With thionyl chloride In tetrahydrofuran; toluene	96.45%

3,5-dichloro-4-aminopyridine (22889-78-7) + 2-(3-benzyloxy-propyl)-3,4-dimethoxy-benzoic acid (1006612-51-6) → 2-(3-benzyloxy-propyl)-N-(3,5-dichloro-pyridin-4-yl)-3,4-dimethoxy-benzamide (1006612-52-7)

Conditions	Yield
Stage #1: 2-(3-benzyloxy-propyl)-3,4-dimethoxy-benzoic acid With benzotriazol-1-ol; dicyclohexyl-carbodiimide In dichloromethane at 40℃; for 2h; Stage #2: 3,5-dichloro-4-aminopyridine With sodium hydride In tetrahydrofuran at 20 - 30℃; for 3.5h;	96%

3-(cyclopropylmethoxy)-4-(difluoromethoxy)-benzoic acid (162401-62-9) + 3,5-dichloro-4-aminopyridine (22889-78-7) → roflumilast (162401-32-3)

Conditions	Yield
Stage #1: 3-(cyclopropylmethoxy)-4-(difluoromethoxy)-benzoic acid With pyridine; 2,4,6-trinitrochlorobenzene In 1,4-dioxane at 20 - 35℃; for 3h; Industrial scale; Stage #2: 3,5-dichloro-4-aminopyridine In 1,4-dioxane for 2h; Reagent/catalyst; Solvent; Temperature; Industrial scale;	95%
Stage #1: 3-(cyclopropylmethoxy)-4-(difluoromethoxy)-benzoic acid With 4-methyl-morpholine; 2-chloro-4,6-dimethoxy-1 ,3,5-triazine In dichloromethane at 0 - 20℃; for 3h; Stage #2: 3,5-dichloro-4-aminopyridine In dichloromethane for 2h; Concentration;	91%
Stage #1: 3-(cyclopropylmethoxy)-4-(difluoromethoxy)-benzoic acid With pivaloyl chloride; sodium carbonate In tetrahydrofuran at 25℃; for 2h; Stage #2: 3,5-dichloro-4-aminopyridine In tetrahydrofuran at 50℃; for 4h; Temperature; Solvent; Reagent/catalyst;	64%
Stage #1: 3-(cyclopropylmethoxy)-4-(difluoromethoxy)-benzoic acid With thionyl chloride In toluene Heating / reflux; Stage #2: 3,5-dichloro-4-aminopyridine With sodium hydride In tetrahydrofuran for 1h; Cooling;	58.6%

3,5-dichloro-4-aminopyridine (22889-78-7) + 3-(difluoromethoxy)-4-(cyclopropylmethoxy)-benzoic acid (162401-69-6) → roflumilast (162401-32-3)

Conditions	Yield
Stage #1: 3-(difluoromethoxy)-4-(cyclopropylmethoxy)-benzoic acid With thionyl chloride In toluene for 2h; Reflux; Stage #2: 3,5-dichloro-4-aminopyridine With sodium hydride In tetrahydrofuran at 15 - 20℃;	95%

3,5-dichloro-4-aminopyridine (22889-78-7) + 3-Phenylpropionic acid (501-52-0) → N-(3,5-dichloropyridin-4-yl)-3-phenylpropanamide (1370286-81-9)

Conditions	Yield
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 1h;	93%
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.5h;	93.3%

3,5-dichloro-4-aminopyridine (22889-78-7) + 4-nitrophenyl 8-methoxy-2,9-dimethyl-1-oxo-1,2,3,4-tetrahydro-β-carboline-5-carboxylate (893555-73-2) → N-(3,5-dichloropyridin-4-yl)-2,9-dimethyl-8-methoxy-1-oxo-1,2,3,4-tetrahydro-β-carboline-5-carboxamide

Conditions	Yield
With sodium hydride at 20℃; for 18h;	90%
With sodium hydride In N,N-dimethyl-formamide at 20℃; for 18h;

3,5-dichloro-4-aminopyridine (22889-78-7) + (3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)(1H-imidazol-1-yl)methanone (1590361-85-5) → roflumilast (162401-32-3)

Conditions	Yield
Stage #1: 3,5-dichloro-4-aminopyridine With cesium fluoride In dimethyl sulfoxide at 90℃; for 3h; Stage #2: (3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)(1H-imidazol-1-yl)methanone In dimethyl sulfoxide at 90 - 95℃; for 6.5h; Reagent/catalyst;	88%

3,5-dichloro-4-aminopyridine (22889-78-7) + p-nitrophenyl 4-difluormethoxy-8-nitrodibenzofuran carboxylic acid ester (883977-47-7) → N-(3,5-dichloro-pyridin-4-yl)-4-difluoromethoxy-8-nitro-dibenzo[b,d]furane-1-carboxamide (685875-02-9)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 25 - 35℃; for 1.83333 - 1.91667h;	86%

3,5-dichloro-4-aminopyridine (22889-78-7) + 3,4-bis(cyclopropylmethoxy)benzoyl chloride (669001-67-6) → 3,4-bis(cyclopropylmethoxy)-N-(3,5-dichloropyridin-4-yl) benzamide

Conditions	Yield
With sodium hydride In acetonitrile at -5 - 0℃; for 1h;	85.3%

3,5-dichloro-4-aminopyridine (22889-78-7) + C17H10F2N2O2S → 3,5-dichloro-4-(4-difluoromethoxy-dibenzo[b,d]-thiophen-1-yl-carboxamido)pyridine

Conditions	Yield
Stage #1: 3,5-dichloro-4-aminopyridine With sodium hydride In DMF (N,N-dimethyl-formamide) at 20℃; for 0.5h; Stage #2: C17H10F2N2O2S In DMF (N,N-dimethyl-formamide)	85%

3,5-dichloro-4-aminopyridine (22889-78-7) + 3-cyclopentyloxy-4-methoxy benzoic acid chloride (144036-19-1) → piclamilast (144035-83-6)

Conditions	Yield
Stage #1: 3,5-dichloro-4-aminopyridine With potassium tert-butylate In toluene at 90℃; Green chemistry; Stage #2: 3-cyclopentyloxy-4-methoxy benzoic acid chloride In toluene for 1h; Reagent/catalyst; Temperature; Solvent; Reflux; Green chemistry;	84%
With sodium hydride 1.) THF, 0.25 h, 2.) THF, RT, 0.5 h; Yield given. Multistep reaction;

3,5-dichloro-4-aminopyridine (22889-78-7) + 7-methoxy-2-phenethyl-benzofuran-4-carbonyl chloride → 7-methoxy-2-phenethyl-benzofuran-4-carboxylic acid (3,5-dichloropyridin-4-yl)-amide

Conditions	Yield
Stage #1: 3,5-dichloro-4-aminopyridine With sodium aluminum diethyl dihydride In tetrahydrofuran; toluene at 50℃; for 1h; Metallation; Stage #2: 7-methoxy-2-phenethyl-benzofuran-4-carbonyl chloride In tetrahydrofuran; toluene at 50℃; for 2h; Acylation;	80%

3,5-dichloro-4-aminopyridine (22889-78-7) + 4-(difluoromethoxy)benzoyl chloride (57320-63-5) → N-(3,5-dichloro-4-pyridyl)-4-(difluoromethoxy)benzamide

Conditions	Yield
With potassium tert-butylate In tetrahydrofuran at 20℃; for 3h; Reagent/catalyst;	80%

3,5-dichloro-4-aminopyridine (22889-78-7) + (3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)(1H-1,2,4-triazol-1-yl)methanone (1601300-21-3) → roflumilast (162401-32-3)

Conditions	Yield
Stage #1: 3,5-dichloro-4-aminopyridine With cesium fluoride In dimethyl sulfoxide at 90℃; for 3h; Stage #2: (3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)(1H-1,2,4-triazol-1-yl)methanone In dimethyl sulfoxide at 90 - 95℃; for 3h;	79%

3,5-dichloro-4-aminopyridine (22889-78-7) + 4-methoxy-2-methylsulfanylpyrimidine-5-carboxylic acid (84332-06-9) → N-(3,5-dichloropyridin-4-yl)-4-methoxy-2-(methylthio)pyrimidine-5-carboxamide

Conditions	Yield
Stage #1: 4-methoxy-2-methylsulfanylpyrimidine-5-carboxylic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 5h; Stage #2: 3,5-dichloro-4-aminopyridine With sodium hydride In dichloromethane; N,N-dimethyl-formamide at 0 - 20℃; for 2h;	75.06%

2-(cyclopentyloxy)-4-iodo-1-methoxybenzene (651023-32-4) + 3,5-dichloro-4-aminopyridine (22889-78-7) + 13C-methyldiphenylsilanecarboxylic acid (1346220-47-0) → C17(13)CH18Cl2N2O3 (1346220-48-1)

Conditions	Yield
Stage #1: 13C-methyldiphenylsilanecarboxylic acid With potassium fluoride In toluene at 70℃; Inert atmosphere; Stage #2: 2-(cyclopentyloxy)-4-iodo-1-methoxybenzene; 3,5-dichloro-4-aminopyridine With palladium diacetate; 1,8-diazabicyclo[5.4.0]undec-7-ene; catacxium A In toluene at 70℃; for 21h; Inert atmosphere;	74%

3,5-dichloro-4-aminopyridine (22889-78-7) + 3-(cyclopropylmethoxy)-4-(difluoromethoxy)-benzaldehyde (151103-09-2) → 3,5-dichloro-N-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzylidene)pyridin-4-amine (1454574-39-0)

Conditions	Yield
Stage #1: 3-(cyclopropylmethoxy)-4-(difluoromethoxy)-benzaldehyde With trifluoroacetic acid; trimethyl orthoformate In toluene at 20 - 30℃; Inert atmosphere; Reflux; Stage #2: 3,5-dichloro-4-aminopyridine With trifluoroacetic acid In toluene at 40 - 110℃;	73%
Stage #1: 3-(cyclopropylmethoxy)-4-(difluoromethoxy)-benzaldehyde With toluene-4-sulfonic acid; trimethyl orthoformate In toluene for 3h; Reflux; Stage #2: 3,5-dichloro-4-aminopyridine With toluene-4-sulfonic acid In toluene at 70 - 80℃; for 30h; Reflux;	23%
With N,O-Bis(trimethylsilyl)trifluoroacetamide; toluene-4-sulfonic acid In acetonitrile for 48h; Reagent/catalyst; Reflux;	70 %Chromat.

3,5-dichloro-4-aminopyridine (22889-78-7) + tert-butyl 4-(4-(2,5-dichloro-4-pyrimidinyl)amino-5-isopropoxy-2-methylphenyl)piperidine-1-carboxylate → 5-chloro-N2(3,5-dichloropyridin-4-yl)-N4(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)pyrimidine-2,4-diamine

Conditions	Yield
With hydrogenchloride In water; isopropyl alcohol at 80℃;	72.9%

3,5-dichloro-4-aminopyridine (22889-78-7) + 1-(4-fluorobenzyl)-7-azaindol-3-yl-glycoxylic acid chloride → AWD-12-353

Conditions	Yield
Stage #1: 3,5-dichloro-4-aminopyridine With sodium hydride In tetrahydrofuran at -5 - 20℃; for 1h; Stage #2: 1-(4-fluorobenzyl)-7-azaindol-3-yl-glycoxylic acid chloride In tetrahydrofuran at 0℃; for 4h; Product distribution / selectivity; Reflux;	72%

3,5-dichloro-4-aminopyridine (22889-78-7) + C49H77N5O15S (1006612-69-6) → C54H79Cl2N7O14S (1006612-25-4)

Conditions	Yield
With water; sodium hydride; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at -5 - 25℃; for 4h;	70%

3,5-dichloro-4-aminopyridine (22889-78-7) + bis(trichloromethyl) carbonate (32315-10-9) + 4-amino-6-(3-bromophenyl)-2-ethylpyridazin-3(2H)-one (1229442-28-7) → 1-(6-(3-bromophenyl)-2-ethyl-3-oxo-2,3-dihydropyridazin-4-yl)-3-(3,5-dichloropyridin-4-yl)urea (1229442-29-8)

Conditions	Yield
Stage #1: bis(trichloromethyl) carbonate; 4-amino-6-(3-bromophenyl)-2-ethylpyridazin-3(2H)-one With triethylamine In dichloromethane for 3h; Inert atmosphere; Stage #2: 3,5-dichloro-4-aminopyridine With sodium hydride In tetrahydrofuran at 20℃;	70%

3,5-dichloro-4-aminopyridine (22889-78-7) + 3,4,5-Trimethoxybenzoyl chloride (4521-61-3) → N-(3,5-dichloropyridin-4-yl)-3,4,5-trimethoxybenzamide (1349175-46-7)

Conditions	Yield
Stage #1: 3,5-dichloro-4-aminopyridine With potassium 2-methylbutan-2-olate In toluene at 90℃; for 0.5h; Stage #2: for 0.5h; Reflux; Stage #3: 3,4,5-Trimethoxybenzoyl chloride Further stages;	70%
Stage #1: 3,5-dichloro-4-aminopyridine With sodium hydride In tetrahydrofuran at 0 - 20℃; for 2h; Inert atmosphere; Stage #2: 3,4,5-Trimethoxybenzoyl chloride In tetrahydrofuran at 0 - 20℃; for 24h; Inert atmosphere;	54%

3,5-dichloro-4-aminopyridine (22889-78-7) + C16H10F3N3O5 (1009603-03-5) → 7-methoxy-2-trifluoromethylpyrazolo[1,5-a]pyridine-4-carboxylic acid (3,5-dichloro pyridin-4-yl)amide (1009601-54-0)

Conditions	Yield
Stage #1: 3,5-dichloro-4-aminopyridine With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 0.5h; Stage #2: C16H10F3N3O5 In N,N-dimethyl-formamide at 0 - 20℃; for 3h;	70%

3,5-dichloro-4-aminopyridine (22889-78-7) + C16H10F3N3O5 → N-(3,5-dichloropyridin-4-yl)-7-methoxy-2-(trifluoromethyl)pyrazolo[1,5-a]pyridine-3-carboxamide (1454802-94-8)

Conditions	Yield
Stage #1: 3,5-dichloro-4-aminopyridine With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 0.5h; Stage #2: C16H10F3N3O5 In N,N-dimethyl-formamide at 0 - 20℃; for 3h;	70%

3,5-dichloro-4-aminopyridine (22889-78-7) → methyl 4-(5-((3,5-dichloropyridin-4-yl)carbamoyl)-2-(difluoromethoxy)phenoxy)benzoate (1422361-57-6)

Conditions	Yield
	70%

3,5-dichloro-4-aminopyridine (22889-78-7) + C13H10BrN3O2 → 1-(6-(3-bromophenyl)-2-ethyl-3-oxo-2,3-dihydropyridazin-4-yl)-3-(3,5-dichloropyridin-4-yl)urea (1229442-29-8)

Conditions	Yield
Stage #1: 3,5-dichloro-4-aminopyridine With sodium hydride In tetrahydrofuran for 2.5h; Stage #2: C13H10BrN3O2 In tetrahydrofuran at 20℃;	70%

3,5-dichloro-4-aminopyridine (22889-78-7) + 2-benzyl-7-methoxy-benzofuran-4-carbonyl chloride → 2-benzyl-7-methoxy-benzofuran-4-carboxylic acid (3,5-dichloropyridin-4-yl)-amide

Conditions	Yield
Stage #1: 3,5-dichloro-4-aminopyridine With sodium aluminum diethyl dihydride In tetrahydrofuran; toluene at 50℃; for 1h; Metallation; Stage #2: 2-benzyl-7-methoxy-benzofuran-4-carbonyl chloride In tetrahydrofuran; toluene at 50℃; for 2h; Acylation;	67%

cis,trans-2,5-dimethoxytetrahydrofuran (696-59-3) + 3,5-dichloro-4-aminopyridine (22889-78-7) → 3,5-dichloro-4-(1H-pyrrol-1-yl)pyridine

Conditions	Yield
With acetic acid at 120℃; for 0.333333h; Inert atmosphere;	63%

Upstream product

• 504-24-5 4-aminopyridine 
• 19798-77-7 4-amino-3-chloropyridine 
• 33216-52-3 3,4,5-trichloropyridine 
• 17122-17-7 4-amino-3,5-dichloro-pyridine-2-carboxylic acid 
• 153463-65-1 3,5-dichloropyridine-4-carbonitrile 
• 7664-41-7 ammonia 
• 7647-01-0 hydrogenchloride 
• 7732-18-5 water 
• 7722-84-1 dihydrogen peroxide 
• 26482-55-3 4-(nitroamino)pyridine 
• 20511-15-3 3-amino-4-chloropyridine 
• 55934-00-4 3,4-dichloropyridine 
• 144036-22-6 3-benzoyloxy-4-methoxybenzoyl chloride 

Downstream Products

• 17228-71-6 3,5-dichloro-4-hydroxypyridine 
• 144035-83-6 piclamilast 
• 185400-42-4 2-butyl-7-methoxy-benzofuran-4-carboxylic acid (3,5-dichloropyridin-4yl)-amide 
• 736970-88-0 N-{[(3,5-dichloro(4-pyridyl))amino]thioxomethyl}benzamide 
• 950192-33-3 4-amino-3-chloro-5-phenylpyridine 
• 166741-48-6 N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-6-fluoro-4-methoxybenzamide 
• 720716-22-3 5-acetyl-4-((3,5-dichloropyridin-4-yl)amino)-2-ethyl-6-phenylpyridazin-3(2H)-one 
• 740872-30-4 N₅-(3,5-dichloro-4-pyridyl)-9-(4-fluorobenzyl)-8-methoxy-2,3,4,9-tetrahydro-1H-5-carbazolecarboxamide 
• 91872-02-5 4-amino-3,5-dichloropyridine-N-oxide 

Relevant articles and documents

Preparation method of pyridine derivative (by machine translation)

To the method, piperidine-4-one hydrochloride is used as a raw material, and a series of pyridine derivatives are obtained through halogenation reaction and elimination reaction. The reaction is eliminated by reacting piperidine-4-one hydrochloride with a specific amount of the 3,5 - halogenating agent in a halogenation 3, 3, 5 - reaction with a halogen-3, 3, 5, 5 - based reaction, followed by reaction with a pyridine derivative of a hydroxyl group, an amino group 4 - or a dimethylamino group, respectively, by eliminating the reaction with a different kind of basic agent. The method is simple and convenient to operate, mild in condition, short in technological process, low in waste water yield, environment-friendly, low in cost and beneficial to green industrial production of the pyridine derivative. (by machine translation)

A method for preparing raw material for roflumilast and detection method

The invention discloses a preparation method and a detection method of a roflumilast material. The preparation method comprises the following steps: mixing 3-cyclopropyl methoxy group-4-difluoro methoxy group benzoic acid SM-1, thionyl chloride, dimethyl formamide with toluene, and carrying out an acylating chlorination reaction to obtain a midbody 1; mixing 3,5-dichloro-4-aminopyridine SM-2, tetrahydrofuran with potassium tert-butoxide and carrying out a salt forming reaction to obtain tetrahydrofuran solution of a midbody 2; and then mixing the midbody 1 and the midbody 2 with tetrahydrofuran, carrying out amidation to obtain a crude product of roflumilast, and refining the crude product of roflumilast to prepare the roflumilast material. Aiming to overcome the shortage of the prior art, the preparation process of the roflumilast material is optimized, so that the curative effect for treating diseases such as chronic obstructive pulmonary disease (COPD) is more remarkable; and besides, a systematic, complete and effective composition identifying and content measuring method is provided, so that the quality of the medicine can be effectively controlled, and the clinical effect is ensured.

COMPOUNDS CONTAINING PHENYL LINKED TO ARYL OR HETEROARYL BY AN ALIPHATIC- OR HETEROATOM-CONTAINING LINKING GROUP

This invention is directed to the pharmaceutical use of phenyl compounds, which are linked to an aryl moiety by various linkages, for inhibiting tumor necrosis factor. The invention is also directed to the compounds, their preparation and pharmaceutical compositions containing these compounds. Furthermore, this invention is directed to the pharmaceutical use of the compounds for inhibiting cyclic AMP phosphodiesterase

Process development of the PDE IV inhibitor 3-(cyclopentyloxy)-n-(3,5-dichloropyrid-4-yl)-4-methoxybenzamide

Development of an industrial process for 3-(cyclopentyloxy)-N-(3,5-dichloropyrid-4-yl)-4-methoxybenzamide, a potent PDE IV type inhibitor, is described. The rapid identification of scalable reaction conditions allowed pilot-scale synthesis of kilogramme quantities for early clinical evaluation. However, as more compound was demanded, better reaction conditions were required in the interests of safety, economics, and environmental impact. This led to the derivation of a high-yielding and very robust procedure which included various safeguards to ensure that high-quality product was obtained and that new trace impurities were effectively removed. The large-scale oxidation of a benzaldehyde derivative to the corresponding benzoic acid using hydrogen peroxide under aqueous alkaline conditions is described.

Synthesis of pluriaminated pyridines

The key reagent 3,5-dichloro-4-pyridinecarbonitrile (1) was used to synthesize 4-aminomethylpyridine derivatives 3,5-disubstituted with various amino groups, very active as inhibitors of diamine oxidase. The study of the reaction allowed to discover conditions for the gradual substitution in good yields of the two chlorine atoms to give symmetrically and unsymmetrically disubstituted derivatives (3), or the substitution of the cyano group, or the formation of amidines. The reduction of the cyano to aminomethyl group in compounds (3) afforded the target bioactive products.

Compounds containing phenyl linked to aryl or heteroaryl by an aliphatic-or heteroatom-containing linking group

This invention is directed to the pharmaceutical use of phenyl compounds, which are linked to an aryl moiety by various linkages, for inhibiting tumor necrosis factor. The invention is also directed to the compounds, their preparation and pharmaceutical compositions containing these compounds. Furthermore, this invention is directed to the pharmaceutical use of the compounds for inhibiting cyclic AMP phosphodiesterase.