115514-77-7

Basic information

• Product Name: 3-Chloro-4-methoxybenzenemethanamine
• Synonyms: 3-chloro-4-methoxybenzenemethanamine;BenzeneMethanaMine, 3-chloro-4-Methoxy-;3-Chloro-4-methoxybenzenemethanamine###3-Chloro-4-methoxybenzyl alcohol
• CAS NO: 115514-77-7
• Molecular Formula: C₈H₁₀ClNO
• Molecular Weight: 171.62
• Mol File: 115514-77-7.mol

Chemical Properties

• Boiling Point: 263.5 °C at 760 mmHg
• Flash Point: 113.2 °C
• Appearance: /
• Density: 1.18 g/cm³
• Vapor Pressure: 0.0102mmHg at 25°C
• Refractive Index: 1.549
• PKA: 9.01±0.10(Predicted)
• CAS DataBase Reference: 3-Chloro-4-methoxybenzenemethanamine(CAS DataBase Reference)
• NIST Chemistry Reference: 3-Chloro-4-methoxybenzenemethanamine(115514-77-7)
• EPA Substance Registry System: 3-Chloro-4-methoxybenzenemethanamine(115514-77-7)

Safety Data

• Hazardous Substances Data: 115514-77-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
3-Chloro-4-methoxybenzenemethanamine is used as a reagent in the synthesis of avanafil (A794670), a medication specifically designed for the treatment of erectile dysfunction. Avanafil works by enhancing the effects of nitric oxide, leading to increased blood flow to the penis and facilitating an erection.
3-Chloro-4-methoxybenzenemethanamine's role in the synthesis of avanafil highlights its importance in the development of therapeutic agents for addressing male sexual health issues. Its unique structural features allow for the creation of molecules with specific biological activities, making it a valuable component in the pharmaceutical industry's pursuit of innovative treatments.

InChI:InChI=1/C8H10ClNO/c1-11-8-3-2-6(5-10)4-7(8)9/h2-4H,5,10H2,1H3

Synthetic route

C14H20ClN4O(1+)*Cl(1-) → (3-chloro-4-methoxyphenyl)methanamine (115514-77-7)

Conditions	Yield
With hydrogenchloride at 50℃; for 1h;	80%

4-methoxy-benzylamine (2393-23-9) → (3-chloro-4-methoxyphenyl)methanamine (115514-77-7)

Conditions	Yield
With chlorine In acetic acid for 1h; Ambient temperature;	34%
With sulfuryl dichloride In acetic acid at 0 - 20℃; for 4h;

(3-chloro-4-methoxyphenyl)methylamine hydrogen chloride (41965-95-1) → (3-chloro-4-methoxyphenyl)methanamine (115514-77-7)

Conditions	Yield
With sodium hydroxide In water; toluene at 25 - 30℃;

3-chloro-4-methoxybenzyl alcohol (14503-45-8) → (3-chloro-4-methoxyphenyl)methanamine (115514-77-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: thionyl chloride / N,N-dimethyl-formamide; dichloromethane / Reflux 2: ethanol / 2 h / 20 - 30 °C / Reflux 3: hydrogenchloride / 1 h / 50 °C View Scheme

4-chloro-2-methanesulfanylpyrimidine-5-carboxylic acid ethyl ester (5909-24-0) + (3-chloro-4-methoxyphenyl)methanamine (115514-77-7) → ethyl 4-[(3-chloro-4-methoxybenzyl)amino]-2-(methylsulfanyl)pyrimidine-5-carboxylate (330785-81-4)

Conditions	Yield
With triethylamine In tetrahydrofuran at 20℃;	100%
With triethylamine In acetone at 20℃; for 3h;	87%
With triethylamine In dichloromethane at 20℃; for 10h;	76%

(3-chloro-4-methoxyphenyl)methanamine (115514-77-7) + C8H10N2O5S → 2-methylsulfonyl-5-ethoxycarbonyl-4-(3-chloro-4-methoxybenzylamino)pyrimidine (372117-76-5)

Conditions	Yield
Stage #1: C8H10N2O5S With N-ethyl-N,N-diisopropylamine; trichlorophosphate In toluene Reflux; Green chemistry; Stage #2: (3-chloro-4-methoxyphenyl)methanamine With N-isopropylethylamine In toluene Reagent/catalyst; Green chemistry;	97.2%
Stage #1: C8H10N2O5S With N-ethyl-N,N-diisopropylamine; trichlorophosphate In toluene Reflux; Stage #2: (3-chloro-4-methoxyphenyl)methanamine With N-isopropylethylamine In toluene	96.8%

(3-chloro-4-methoxyphenyl)methanamine (115514-77-7) → 3-chloro-4-methoxy-benzaldehyde (4903-09-7)

Conditions	Yield
With oxygen; [5,6]fullerene-C70 In chloroform; toluene at 20℃; for 24h; Sealed tube; Irradiation;	96%

(3-chloro-4-methoxyphenyl)methanamine (115514-77-7) + C13H16ClN3O4 → C21H25ClN4O5

Conditions	Yield
With sodium carbonate In N,N-dimethyl-formamide at 60℃; for 4h; Reflux;	95%

(3-chloro-4-methoxyphenyl)methanamine (115514-77-7) + C6H6N2O5S + 2-aminomethylpyrimidine (75985-45-4) → 4-[(3-chloro-4-methoxybenzyl)amino]-2-methanesulfonyl-N-(2-pyrimidinylmethyl)-5-pyrimidinecarboxamide

Conditions	Yield
Stage #1: C6H6N2O5S With N-ethyl-N,N-diisopropylamine; trichlorophosphate In toluene Reflux; Stage #2: 2-aminomethylpyrimidine With N-ethyl-N,N-diisopropylamine In toluene at -8℃; Stage #3: (3-chloro-4-methoxyphenyl)methanamine With N-ethyl-N,N-diisopropylamine In toluene at 0℃; Temperature;	93.8%

(3-chloro-4-methoxyphenyl)methanamine (115514-77-7) + 5-(4-{[4-(acetyloxy)piperidin-1-yl]methyl}-1,3-thiazol-2-yl)-1-ethyl-1H-indole-3-carboxylic acid → 1-((2-(3-(3-(3-chloro-4-methoxyphenyl)ureido)-1-ethyl-1H-indol-5-yl)thiazol-4-yl)methyl )piperidin-4-yl acetate

Conditions	Yield
Stage #1: 5-(4-{[4-(acetyloxy)piperidin-1-yl]methyl}-1,3-thiazol-2-yl)-1-ethyl-1H-indole-3-carboxylic acid With diphenyl phosphoryl azide; triethylamine In toluene at 20℃; for 0.5h; Stage #2: (3-chloro-4-methoxyphenyl)methanamine In toluene for 2h; Reflux;	75%

(3-chloro-4-methoxyphenyl)methanamine (115514-77-7) + 3-(tert-butyl)-1-methyl-1H-pyrazole-5-carboxylic acid (175277-11-9) → 3-(tert-butyl)-N-(3-chloro-4-methoxybenzyl)-1-methyl-1H-pyrazole-5-carboxamide

Conditions	Yield
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20 - 25℃; for 12h; Inert atmosphere;	66%

4-hydroxy-6-methyl-2-pyron (675-10-5) + (3-chloro-4-methoxyphenyl)methanamine (115514-77-7) → 1-(3-chloro-4-methoxybenzyl)-4-hydroxy-6-methylpyridin-2(1H)-one (883507-92-4)

Conditions	Yield
In water at 100℃; for 5.33333h; Heating / reflux;	63%

1,4-dichlorophthalazine (4752-10-7) + (3-chloro-4-methoxyphenyl)methanamine (115514-77-7) → 4-chloro-N-[(3-chloro-4-methoxyphenyl)methyl]phthalazin-1-amine

Conditions	Yield
With sodium carbonate In N,N-dimethyl-formamide at 130℃;	62%

tert-butyl 10-chloro-8-cyano-3,4-dihydrobenzo[b][1,6]-naphthyridine-2(1H)-carboxylate (1448419-27-9) + (3-chloro-4-methoxyphenyl)methanamine (115514-77-7) → tert-butyl 10-((3-chloro-4-methoxybenzyl)amino)-8-cyano-3,4-dihydrobenzo[b][1,6]naphthyridine-2-(1H)-carboxylate (1448419-28-0)

Conditions	Yield
With triethylamine; sodium iodide In 1-methyl-pyrrolidin-2-one at 130℃; Inert atmosphere;	49%

(3-chloro-4-methoxyphenyl)methanamine (115514-77-7) + 3-bromo-5-(trifluoromethyl)-1-cyclopentyl-1H-indazole → N-[(3-chloro-4-methoxyphenyl)methyl]-1-cyclopentyl-5-(trifluoromethyl)-1H-indazol-3-amine

Conditions	Yield
With dicyclohexyl-(2′,4′,6′-triisopropyl-3,6-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine; palladium diacetate; caesium carbonate In 1,4-dioxane at 120℃; Buchwald-Hartwig Coupling; Inert atmosphere; Sealed tube;	44%

(3-chloro-4-methoxyphenyl)methanamine (115514-77-7) + 8-bromo-7-(3-chloropropyl)-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (98408-17-4) → 9-(3-chloro-4-methoxybenzyl)-1,3-dimethyl-6,7,8,9-tetrahydropyrimido[2,1-f]purine-2,4(1H,3H)-dione

Conditions	Yield
In propan-1-ol at 160℃; under 7500.75 Torr; for 1h; Microwave irradiation; Sealed tube;	41%

(3-chloro-4-methoxyphenyl)methanamine (115514-77-7) + (±)-9-tosyl-9-azabicyclo[4.2.1]nonane-2-carboxylic acid → (±)-N-(3-chloro-4-methoxybenzyl)-9-tosyl-9-azabicyclo[4.2.1]nonane-2-carboxamide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; Inert atmosphere;	31%

styrene oxide (96-09-3) + (3-chloro-4-methoxyphenyl)methanamine (115514-77-7) → N-(3-chloro-4-methoxybenzyl)-2-hydroxyphenethylamine (115514-78-8)

Conditions	Yield
In acetonitrile for 16h; Heating;	25%

(3-chloro-4-methoxyphenyl)methanamine (115514-77-7) + spirothiazamenthane → N-(3-chloro-4-methoxybenzyl)-4,4,8-trimethyl-1-thia-3-azaspiro[4.5]dec-2-en-2-amine

Conditions	Yield
With toluene-4-sulfonic acid In toluene at 150℃; for 4h; Microwave irradiation;	18%

(3-chloro-4-methoxyphenyl)methanamine (115514-77-7) + 2-(4-((1H-pyrazol-1-yl)methyl)benzyl)-4-chloro-2H-pyrazolo[3,4-d]pyrimidine → 2-(4-((1H-pyrazol-1-yl)methyl)benzyl)-N-(3-chloro-4-methoxybenzyl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine

Conditions	Yield
at 120℃; for 3h;	5%

(3-chloro-4-methoxyphenyl)methanamine (115514-77-7) + 5-chloro-8-[5-(3-dimethylamino-pyrrolidine-1-sulfonyl)-2-propoxy-phenyl]-2-(4-methoxy-benzyl)-2,7-dihydro-2,3,4,7,9-pentaaza-cyclopenta[a]naphthalen-6-one (384835-99-8) → 5-(3-chloro-4-methoxy-benzylamino)-8-[5-(3-dimethylamino-pyrrolidine-1-sulfonyl)-2-propoxy-phenyl]-2-(4-methoxy-benzyl)-2,7-dihydro-2,3,4,7,9-pentaaza-cyclopenta[a]naphthalen-6-one (459124-67-5)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In propan-1-ol for 4h; Heating;

4-(tert-butoxycarbonylamino)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxylic acid (956460-96-1) + (3-chloro-4-methoxyphenyl)methanamine (115514-77-7) → C25H31ClN6O4

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In 1-methyl-pyrrolidin-2-one at 60℃; for 16h;

(3-chloro-4-methoxyphenyl)methanamine (115514-77-7) + 4,7-dichloro-6-nitro-quinazoline (162012-71-7) → C16H12Cl2N4O3 (1007308-59-9)

Conditions	Yield
With triethylamine In isopropyl alcohol
Stage #1: (3-chloro-4-methoxyphenyl)methanamine; 4,7-dichloro-6-nitro-quinazoline With triethylamine; N,N-dimethyl-formamide In isopropyl alcohol at 20℃; for 17h; Stage #2: With sodium hydrogencarbonate In water; ethyl acetate

(3-chloro-4-methoxyphenyl)methanamine (115514-77-7) → 5-(3-chloro-4-methoxy-benzylamino)-8-[5-(3-dimethylamino-pyrrolidine-1-sulfonyl)-2-propoxy-phenyl]-2,7-dihydro-2,3,4,7,9-pentaaza-cyclopenta[a]naphthalen-6-one

Conditions	Yield
Multi-step reaction with 2 steps 1: DIEA / propan-1-ol / 4 h / Heating 2: TFA / 1 h / 60 °C View Scheme

(3-chloro-4-methoxyphenyl)methanamine (115514-77-7) → 7-chloro-6-hydroxy-4-phenyl-1,2,3,4-tetrahydroisoquinoline (115514-80-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 25 percent / acetonitrile / 16 h / Heating 2: 92 percent / H2SO4 / 2 h / Ambient temperature 3: 21 percent / 48percent HBr / 12 h / 100 °C View Scheme

(3-chloro-4-methoxyphenyl)methanamine (115514-77-7) → 7-chloro-6-methoxy-4-phenyl-1,2,3,4-tetrahydroisoquinoline (115514-79-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 25 percent / acetonitrile / 16 h / Heating 2: 92 percent / H2SO4 / 2 h / Ambient temperature View Scheme

(3-chloro-4-methoxyphenyl)methanamine (115514-77-7) → sch 23390 (115514-82-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: 25 percent / acetonitrile / 16 h / Heating 2: 92 percent / H2SO4 / 2 h / Ambient temperature 3: 74 percent / formic acid / 4 h / Heating 4: 83 percent / 48percent HBr / 12 h / 100 °C View Scheme

(3-chloro-4-methoxyphenyl)methanamine (115514-77-7) → N-methyl-7-chloro-6-methoxy-4-phenyl-1,2,3,4-tetrahydroisoquinoline (115514-81-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 25 percent / acetonitrile / 16 h / Heating 2: 92 percent / H2SO4 / 2 h / Ambient temperature 3: 74 percent / formic acid / 4 h / Heating View Scheme

Methyl 3-(4-chlorobenzothieno[2, 3-d]pyrimid in-2-yl)propionate (247909-63-3) + (3-chloro-4-methoxyphenyl)methanamine (115514-77-7) → methyl 3-[4-(3-chloro-4-methoxybenzylamino)benzothieno-[2,3-d]pyrimidin-2-yl]propionate (247909-64-4)

Conditions	Yield
In 1-methyl-pyrrolidin-2-one at 110℃; for 5h;

methyl 4-(4-chlorobenzothieno[2, 3-d]pyrimidin-2-yl)phenylcarboxylate + (3-chloro-4-methoxyphenyl)methanamine (115514-77-7) → methyl 4-[4-(3-chloro-4-methoxybenzylamino)-[1]benzothieno[2,3-d]pyrimidin-2-yl]benzoate

Conditions	Yield
In 1-methyl-pyrrolidin-2-one at 110℃; for 4h;
With hydrogen sulfide; dimethyl amine; trichlorophosphate In 1-methyl-pyrrolidin-2-one

(3-chloro-4-methoxyphenyl)methanamine (115514-77-7) → 4-(aminomethyl)-2-chlorophenol hydrobromide (859517-85-4)

Conditions	Yield
With water; hydrogen bromide at 133℃; for 4h;

2,6-dichloropyridine-3-carboxylic acid (38496-18-3) + (3-chloro-4-methoxyphenyl)methanamine (115514-77-7) → 2-chloro-5-carboxy-6-(3-chloro-4-methoxybenzylamino)pyridine (372117-97-0)

Conditions	Yield
With 1-methyl-pyrrolidin-2-one; potassium carbonate; copper(I) bromide at 120℃; for 2.5h;

Upstream product

• 14503-45-8 3-chloro-4-methoxybenzyl alcohol 
• 41965-95-1 (3-chloro-4-methoxyphenyl)methylamine hydrogen chloride 
• 2393-23-9 4-methoxy-benzylamine 

Downstream Products

• 459124-67-5 5-(3-chloro-4-methoxy-benzylamino)-8-[5-(3-dimethylamino-pyrrolidine-1-sulfonyl)-2-propoxy-phenyl]-2-(4-methoxy-benzyl)-2,7-dihydro-2,3,4,7,9-pentaaza-cyclopenta[a]naphthalen-6-one 
• 330785-81-4 ethyl 4-[(3-chloro-4-methoxybenzyl)amino]-2-(methylsulfanyl)pyrimidine-5-carboxylate 
• 247909-64-4 methyl 3-[4-(3-chloro-4-methoxybenzylamino)benzothieno-[2,3-d]pyrimidin-2-yl]propionate 
• 859517-85-4 4-(aminomethyl)-2-chlorophenol hydrobromide 
• 372117-97-0 2-chloro-5-carboxy-6-(3-chloro-4-methoxybenzylamino)pyridine 
• 372117-94-7 3-ethoxycarbonyl-4-(3-chloro-4-methoxybenzylamino)-6-chloropyridine 
• 247568-34-9 2-fluoro-5-nitro-N-(1,3-benzodioxol-5-ylmethyl)benzamide 
• 247570-08-7 N-(3-chloro-4-methoxybenzyl)-2-fluoro-5-(trifluoromethyl)benzamide 
• 299428-87-8 5,6,7,8-tetrahydro-4-[(3-chloro-4-methoxy)benzylamino]-7-ethoxycarbonyl-2-(3-pyridyl)pyrido[4',3':4,5]thieno[2,3-d]pyrimidine 
• 299428-96-9 ethyl 5,6,7,8-tetrahydro-4-[(3-chloro-4-methoxy)benzylamino]-7-methylpyrido[4',3':4,5]thieno[2,3-d]pyrimidine-2-carboxylate 
• 408322-36-1 4-[(3-chloro-4-methoxy)benzylamino]-6-ethoxycarbonyl-5-methyl-2-(3-pyridyl)-thieno[2,3-d]pyrimidine 
• 408322-41-8 4-[(3-chloro-4-methoxy)benzylamino]-2-ethoxycarbonyl-5-methyl-6-(3-pyridyl)-thieno[2,3-d]pyrimidine 
• 408322-44-1 4-[(3-chloro-4-methoxy)benzylamino]-5-methyl-2-(3-pyridyl)-6-(4-pyridyl)-thieno[2,3-d]pyrimidine 
• 330785-82-5 4-(3-chloro-4-methoxybenzylamino)-5-ethoxycarbonyl-2-methylsulfinylpyrimidine 

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