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

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

Downstream Products

• 115514-78-8 N-(3-chloro-4-methoxybenzyl)-2-hydroxyphenethylamine 
• 247909-64-4 methyl 3-[4-(3-chloro-4-methoxybenzylamino)benzothieno-[2,3-d]pyrimidin-2-yl]propionate 
• 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 
• 329746-19-2 methyl 3-[7-(3-chloro-4-methoxybenzylamino)-1-methyl-3-propyl-1H-pyrazolo[4,3-d]-pyrimidin-5-yl]propionate 
• 372117-97-0 2-chloro-5-carboxy-6-(3-chloro-4-methoxybenzylamino)pyridine 
• 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 

Relevant articles and documents

Preparation method of avanafil important intermediate

The invention provides a preparation method of an avanafil important intermediate. The target compound (3-chloro-4-methoxybenzylamine) is prepared according to a route shown as the specification. The preparation method provided by the invention has the advantages of cheap and easily available raw materials, short technical route, mild reaction conditions, low equipment requirement, and small health hazard to operators, and is in line with the idea of green chemistry. The method has high yield, and can obtain product with high purity, thus being suitable for industrial production.

PROCESS FOR THE PREPARATION OF (S)-4-[(3-CHLORO-4-METHOXYBENZYL)AMINO]-2-[2- (HYDROXYMETHYL)-1-PYRROLIDINYL]-N-(2-PYRIMIDINYL METHYL-5-PYRIMIDINE CARBOXAMIDE

The present invention relates to an improved process for the preparation of (S)-4-[(3- chloro-4-methoxybenzyl)amino]-2-[2-(hydroxymethyl)-1-pyrrolidinyl]-N-(2-pyrimidinyl ethyl)- 5-pyrimidine carboxamide compound of formula-1 represented by the following structural formula.

2-(AMINO-SUBSTITUTED)-4-ARYL PYRAMIDINES AND RELATED COMPOUNDS USEFUL FOR TREATING INFLAMMATORY DISEASES

A heterocyclic inhibitor having the formula (I), with the variables defined herein, which is useful for treating inflammatory and other physiological disorders in which PKC-theta isoform plays a role.

Synthesis and pharmacological characterization of 1-phenyl-, 4-phenyl-, and 1-benzyl-1,2,3,4-tetrahydroisoquinolines as dopamine receptor ligands

A series of 1-phenyl-, 4-phenyl-, and 1-benzyl-1,2,3,4-tetrahydroisoquinolines have been prepared as ring-contracted analogues of the prototypical D1 dopamine receptor antagonist SCH23390 [(R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3 benzazepine]. The affinity and selectivity of these isoquinolines for D1 receptors was determined by three biochemical endpoints in membrane homogenates prepared from rat corpus striatum: the potency to compete for [3H]SCH23390 binding sites; the potency to compete for [3H]spiperone (a D2 receptor ligand) binding sites; and effects on dopamine-stimulated adenylate cyclase. Competitive binding measurements at D1 sites showed SCH23390 to possess the highest affinity, followed by 1-phenyl > 1-benzyl > 4-phenyl for the isoquinolines. These results were highly correlated with the ability of the test compounds to antagonize dopamine-stimulated adenylate cyclase (r = 0.98). None of the compounds alone stimulated cAMP formation at concentrations of 10 nM to 100 μM. D2 competition binding showed the 1-benzyl derivative to possess the highest affinity, followed by 4-phenyl > SCH23390 > 1-phenyl. The tertiary 1-phenyl derivative was more potent than the secondary 1-phenyl analogue in all assays. Interestingly, resolution and single-crystal X-ray analysis of the tertiary N-methyl-1-phenyltetrahydroisoquinoline showed the most active enantiomer to possess the S absolute configuration, in contrast to the benzazepine (R)-SCH23390.