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
• Article Data: 4

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

3-Chloro-4-methoxybenzylamine is a reagent in the synthesis of avanafil (A794670) which is used for the treatment of erectile dysfunction.

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

• 115514-78-8 N-(3-chloro-4-methoxybenzyl)-2-hydroxyphenethylamine 
• 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 
• 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 
• 372117-97-0 2-chloro-5-carboxy-6-(3-chloro-4-methoxybenzylamino)pyridine 
• 247909-64-4 methyl 3-[4-(3-chloro-4-methoxybenzylamino)benzothieno-[2,3-d]pyrimidin-2-yl]propionate 
• 726205-60-3 2-chloro-4-(3-chloro-4-methoxybenzylamino)nicotinic acid ethyl ester 
• 372115-95-2 4-(3-chloro-4-methoxybenzylamino)-5-methoxycarbonyl-6-(4-hydroxypiperidin-1-yl)-2-(5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-7-yl)pyrimidine 
• 883507-92-4 1-(3-chloro-4-methoxybenzyl)-4-hydroxy-6-methylpyridin-2(1H)-one 
• 330786-10-2 2-methoxycarbonyl-3-(3-chloro-4-methoxybenzylamino)-5-chloropyrazine 
• 372117-84-5 2-chloro-4-(3-chloro-4-methoxybenzylamino)-5-[(hydroxy)(2-pyridyl)methyl]pyrimidine 
• 372118-31-5 4-(3-chloro-4-methoxybenzylamino)-5-carboxy-6-chloro-2-methylthiopyrimidine 
• 329746-19-2 methyl 3-[7-(3-chloro-4-methoxybenzylamino)-1-methyl-3-propyl-1H-pyrazolo[4,3-d]-pyrimidin-5-yl]propionate 

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