608-07-1

Basic information

• Product Name: 5-Methoxytryptamine
• Synonyms: ART-CHEM-BB B028531;AURORA KA-7772;BIO-FARMA BF000967;METHOXYTRYPTAMINE, 5-;MEXAMINE;MEXAMINE HYDROCHLORIDE;1H-Indole-3-ethanamine, 5-methoxy-;3-(2-aminoethyl)-5-methoxy-indol
• CAS NO: 608-07-1
• Molecular Formula: C₁₁H₁₄N₂O
• Molecular Weight: 190.24166
• EINECS: 200-637-6
• Product Categories: Indole/indoline/oxindole;Indole and Indoline;PHARMACEUTICAL INTERMEDIATES;Tryptamines;pharmacetical;Indoline & Oxindole;Indoles;Building Blocks;Heterocyclic Building Blocks;Non-Chiral heterocyclic compounds;Agonists;Amines;Heterocycles;Indole Derivatives;Intermediates & Fine Chemicals;Neurochemicals;Pharmaceuticals;Bioactive Small Molecules;Building Blocks;C11;Cell Biology;Chemical Synthesis;Heterocyclic Building Blocks;M
• Mol File: 608-07-1.mol
• Article Data: 42

Chemical Properties

• Melting Point: 245-250 °C (dec.)(lit.)
• Boiling Point: 325.75°C (rough estimate)
• Appearance: white/crystalline
• Density: 1.0815 (rough estimate)
• Refractive Index: 1.5700 (estimate)
• Storage Temp.: 2-8°C
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 16.91±0.30(Predicted)
• Merck: 13,6032
• BRN: 145587
• CAS DataBase Reference: 5-Methoxytryptamine(CAS DataBase Reference)
• NIST Chemistry Reference: 5-Methoxytryptamine(608-07-1)
• EPA Substance Registry System: 5-Methoxytryptamine(608-07-1)

Safety Data

• Hazard Codes: Xn
• Statements: 22-36/37/38-20/21/22
• Safety Statements: 36-26
• WGK Germany: 3
• RTECS: NL4110000
• F: 8
• Hazardous Substances Data: 608-07-1(Hazardous Substances Data)

Usage

Description

5-Methoxytryptamine (5-MT), also known as mexamine, is a tryptamine derivative closely related to the neurotransmitters serotonin and melatonin. 5-MT has been shown to occur naturally in the body in low levels.It is biosynthesized via the deacetylation of melatonin in the pineal gland.The protective effect of 5-methoxytryptamine (a metabolite of melatonin) in human keratinocytes against ultraviolet B (UVB) radiation was studied.Melatonin and its metabolites ameliorate ultraviolet B-induced damage in human epidermal keratinocytes.

Uses

5-Methoxytryptamine (Mexamine, Methoxytryptamine) is a tryptamine derivative that is closely related to the neurotransmitter Melatonin (M215000) and Serotonin (S274980). It acts as a full agonist at the 5-HT1, 5-HT2, 5-HT4, 5-HT6, and 5-HT7 receptors but has no affinity for the 5-HT3 receptor.

Definition

ChEBI: 5-methoxytryptamine is a member of the class of tryptamines that is the methyl ether derivative of serotonin. It has a role as a serotonergic agonist, a human metabolite, a mouse metabolite, a 5-hydroxytryptamine 2A receptor agonist, a 5-hydroxytryptamine 2C receptor agonist, a 5-hydroxytryptamine 2B receptor agonist, an antioxidant, a radiation protective agent, a neuroprotective agent and a cardioprotective agent. It is a member of tryptamines, an aromatic ether and a primary amino compound. It derives from a serotonin. It is a conjugate base of a 5-methoxytryptamine(1+).

Application

5-Methoxytryptamine was used as an agonist in the study of pharmacological profile of the 5-hydroxytryptamine 1 receptor.Reactant for preparation of:Carboline disaccharide domain of shishijimicin AMelatonin analogs for the reduction of intraocular pressure5-HT4 receptor ligandsinhibitors of sortase A and isocitrate lyaseTherapeutic agents for treatment of ischemia/reperfusion (I/R) injuryAurora and epidermal growth factor receptor kinase inhibitorsAgents for the treatment of human papillomavirus infectionManzamine analogues for the control of neuroinflammation and cerebral infectionsInhibitors of pro-inflammatory cytokinesTacrine-melatonin hybrids as multifunctional agents for alzheimer′s disease

General Description

The protective effect of 5-methoxytryptamine (a metabolite of melatonin) in human keratinocytes against ultraviolet B (UVB) radiation was studied.

Synthesis

5-Methoxytryptamine (358) was synthesized from 3-(2-iodoethyl)-5-methoxyindole (176) by reaction with 1-methyl-benzylamine (MeCN, 24 h, RT) and subsequent catalytic debenzylation of 44 (H2, Pd/C, EtOH, 24 h, RT, 4 bar). The resulting 5-methoxytryptamine (358 was then reacted with 4-bromobenzoylchloride (THF, NEt3, RT, ON) and the resulting tryptamide 359 was reduced with aluminum hydride to N-(4-bromobenzyl)-5-methoxytryptamine (19) (LiAlH4, AlCl3, Et2O, 5 h, RT), which was isolated as its hydrogen oxalate salt.

Clinical claims and research

The effects of the 5-HT receptor agonist, 5-methoxytryptamine, on plasma glucose levels were investigated in rats. 5-Methoxytryptamine induced a significant hyperglycemia above the dosage of 1 mg/kg. 5-Methoxytryptamine-induced hyperglycemia was antagonized by pretreatment with the 5-HT1 and 5-HT2 receptor antagonist, methysergide, or the 5-HT2A receptor antagonist, ketanserin, whereas the 5-HT3 and 5-HT4 receptor antagonist, tropisetron, and the 5-HT4 receptor antagonist, SDZ 205-557 (2-methoxy-4-amino-5-chloro-benzoic acid 2-(diethylamino) ethyl ester), showed no effect. In addition, the peripheral 5-HT2 receptor antagonist, xylamidine, reduced 5-methoxytryptamine-induced hyperglycemia. Hyperglycemia induced by the 5-HT receptor agonist, 5-methoxytryptamine, in rats: involvement of the peripheral 5-HT2A receptor.

InChI:InChI=1/C11H11NO3/c1-15-8-2-3-10-9(5-8)7(6-12-10)4-11(13)14/h2-3,5-6,12H,4H2,1H3,(H,13,14)

Synthetic route

5-methoxy-3-(2-nitroethyl)-1H-indole (68935-49-9) → 2-(5-methoxyindol-3-yl)ethylamine (608-07-1)

Conditions	Yield
With palladium on activated charcoal; hydrogen In methanol at 20℃;	99%
With hydrogen; palladium on activated charcoal In ethanol under 2585.7 Torr; for 12h;

methyl N-[2-(5-methoxy-1H-indol-3-yl)ethyl]carbamate (67199-10-4) → 2-(5-methoxyindol-3-yl)ethylamine (608-07-1)

Conditions	Yield
With sodium hydroxide In methanol for 4h; Hydrolysis; decarboxylation; Heating;	99%
With water Hydrolysis;
With sodium hydroxide Heating;

2-ethoxycarbonyl-3-(2-phthalimidoethyl)-5-methoxyindole (55747-53-0) → 2-(5-methoxyindol-3-yl)ethylamine (608-07-1)

Conditions	Yield
Stage #1: 2-ethoxycarbonyl-3-(2-phthalimidoethyl)-5-methoxyindole With water; sodium hydroxide at 88 - 90℃; Stage #2: With hydrogenchloride In water at 10 - 110℃; Temperature;	99%
Multi-step reaction with 2 steps 1: 10 percent aq. NaOH / 0.08 h / Heating; microwave irradiation 2: 20 percent H2SO4 / 0.17 h / Heating; microwave irradiation View Scheme
With potassium hydroxide for 3h; Reflux;	57 g

5-methoxy-N-acetyl-tryptamine (73-31-4) → 2-(5-methoxyindol-3-yl)ethylamine (608-07-1)

Conditions	Yield
With ammonium bromide; ethylenediamine at 100℃; for 7h; Microwave irradiation;	89%
With sulfuric acid In water for 8h; Heating;	69.7%
With sodium hydroxide In 2-methyl-propan-1-ol

2-(1-methanesulfonyl-5-methoxy-1H-indol-3-yl)ethylamine (627086-10-6) → 2-(5-methoxyindol-3-yl)ethylamine (608-07-1)

Conditions	Yield
With potassium hydroxide In methanol for 9h; Heating;	84%

5-methoxy-3-(2-nitro-vinyl)-indole (61675-19-2) → 2-(5-methoxyindol-3-yl)ethylamine (608-07-1)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃; for 40h;	73%
With lithium aluminium tetrahydride In tetrahydrofuran Heating;
Stage #1: 5-methoxy-3-(2-nitro-vinyl)-indole With lithium aluminium tetrahydride In tetrahydrofuran at 20℃; Inert atmosphere; Stage #2: With water In tetrahydrofuran at 0℃;

2-(1-benzyl-5-methoxy-1H-indol-3-yl)ethylamine (40619-73-6) → 2-(5-methoxyindol-3-yl)ethylamine (608-07-1)

Conditions	Yield
With sodium In tetrahydrofuran; ammonia at -33℃; for 1.5h;	66%

N-(2-(5-methoxy-1H-indol-3-yl)ethyl)-4-methylbenzenesulfonamide (102016-76-2) → 2-(5-methoxyindol-3-yl)ethylamine (608-07-1)

Conditions	Yield
With ammonia; sodium In tetrahydrofuran at -78℃; for 0.25h;	65%

5-methoxylindole (1006-94-6) + L-serin (56-45-1) → 2-(5-methoxyindol-3-yl)ethylamine (608-07-1)

Conditions	Yield
Stage #1: 5-methoxylindole; L-serin With engineered tryptophan synthase In methanol; aq. phosphate buffer at 75℃; for 12h; pH=8.0; Enzymatic reaction; Stage #2: With pyridoxal 5'-phosphate; Ruminococcus gnavus L-tryptophan decarboxylase In methanol; aq. phosphate buffer at 37℃; pH=8.0; Enzymatic reaction;	14%

5-methoxylindole (1006-94-6) + methyl magnesium iodide (917-64-6) + diethyl ether (60-29-7) + chloroacetonitrile (107-14-2) → 2-(5-methoxyindol-3-yl)ethylamine (608-07-1)

Conditions	Yield
und Erwaermen des Reaktionsprodukts Natrium in Aethanol;

5-methoxylindole (1006-94-6) + methyl magnesium iodide (917-64-6) + chloroacetonitrile (107-14-2) → 2-(5-methoxyindol-3-yl)ethylamine (608-07-1)

Conditions	Yield
With diethyl ether Erwaermen des Reaktionsprodukts mit Natrium und Aethanol;

(5-methoxy-2-oxo-2,3-dihydro-1H-indol-3-yl)acetonitrile (70351-49-4) → 2-(5-methoxyindol-3-yl)ethylamine (608-07-1)

Conditions	Yield
With 2-methyl-propan-1-ol; sodium

5-methoxytryptamine-2-carboxylic acid (52648-13-2) → 2-(5-methoxyindol-3-yl)ethylamine (608-07-1)

Conditions	Yield
With hydrogenchloride

4-Methoxyphenylhydrazine (3471-32-7) + 4-amino-butyraldehyde diethyl acetate → 2-(5-methoxyindol-3-yl)ethylamine (608-07-1)

Conditions	Yield
With zinc(II) chloride at 180℃;

5-methoxy-3-indoleglyoxylylamide (52055-22-8) → 2-(5-methoxyindol-3-yl)ethylamine (608-07-1)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran for 8h; Heating;
With lithium aluminium tetrahydride In tetrahydrofuran for 18h; Reflux;

5-methoxy-3-(2-phthalimido-ethyl)-indole-2-carboxylic acid (55747-60-9) → 2-(5-methoxyindol-3-yl)ethylamine (608-07-1)

Conditions	Yield
With sulfuric acid for 0.166667h; Heating; microwave irradiation;

tryptamine (61-54-1) + phenyl halide → 2-(5-methoxyindol-3-yl)ethylamine (608-07-1)

Conditions	Yield
Multi-step reaction with 5 steps 1: 100 percent / Et3N 2: Et3SiH / trifluoroacetic acid 3: 63 percent / Na2WO4*2H2O; aq. H2O2 / methanol; H2O 4: 85 percent / BF3 5: NaOH / Heating View Scheme

methyl 2-(1-H-indol-3-yl)ethylcarbamate (58635-45-3) → 2-(5-methoxyindol-3-yl)ethylamine (608-07-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: Et3SiH / trifluoroacetic acid 2: 63 percent / Na2WO4*2H2O; aq. H2O2 / methanol; H2O 3: 85 percent / BF3 4: NaOH / Heating View Scheme
Multi-step reaction with 4 steps 1: 97 percent / Et3SiH / trifluoroacetic acid / 3 h / 60 °C 2: 65 percent / H2O2 / Na2WO4*2H2O / methanol; H2O / 0.5 h / 20 °C 3: 94 percent / BF3 / 0.67 h / Heating 4: 99 percent / aq. NaOH / methanol / 4 h / Heating View Scheme

2,3-dihydro-Nb-methoxycarbonyltryptamine (180910-64-9) → 2-(5-methoxyindol-3-yl)ethylamine (608-07-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: 63 percent / Na2WO4*2H2O; aq. H2O2 / methanol; H2O 2: 85 percent / BF3 3: NaOH / Heating View Scheme
Multi-step reaction with 3 steps 1: 65 percent / H2O2 / Na2WO4*2H2O / methanol; H2O / 0.5 h / 20 °C 2: 94 percent / BF3 / 0.67 h / Heating 3: 99 percent / aq. NaOH / methanol / 4 h / Heating View Scheme

1-hydroxy-Nb-methoxycarbonyltryptamine (180910-53-6) → 2-(5-methoxyindol-3-yl)ethylamine (608-07-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / BF3 2: NaOH / Heating View Scheme
Multi-step reaction with 2 steps 1: 94 percent / BF3 / 0.67 h / Heating 2: 99 percent / aq. NaOH / methanol / 4 h / Heating View Scheme
Multi-step reaction with 2 steps 1: 85 percent / BF3*MeOH / 0.17 h / Heating 2: H2O View Scheme

5-methoxylindole (1006-94-6) → 2-(5-methoxyindol-3-yl)ethylamine (608-07-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: POCl3 / 0 °C 2: NH4OAc / 70 °C 3: LiAlH4 / tetrahydrofuran / Heating View Scheme
Multi-step reaction with 3 steps 1: diethyl ether / 6 h / Heating 2: NH3 / dioxane / 8 h / 20 °C 3: lithium aluminum hydride / tetrahydrofuran / 8 h / Heating View Scheme
Multi-step reaction with 5 steps 1.1: BuLi / tetrahydrofuran; hexane / 0.25 h / -10 °C 1.2: tetrahydrofuran; hexane / 3 h / 0 °C 2.1: 5.4 g / NBS / tetrahydrofuran; hexane / 3 h / -78 °C 3.1: t-BuLi / pentane; diethyl ether / 0.17 h / -78 °C 3.2: CuBr*SMe2 / pentane; diethyl ether / 0.25 h / -78 °C 3.3: 50 percent / BF3*Et2O / pentane; diethyl ether / 4 h / -78 °C 4.1: 89 percent / Bu4NF / tetrahydrofuran / 0.17 h / 20 °C 5.1: 65 percent / NH3; Na / tetrahydrofuran / 0.25 h / -78 °C View Scheme

5-methoxyindole-3-carboxaldehyde (10601-19-1) → 2-(5-methoxyindol-3-yl)ethylamine (608-07-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: NH4OAc / 70 °C 2: LiAlH4 / tetrahydrofuran / Heating View Scheme
Multi-step reaction with 3 steps 1: ammonium acetate / benzene / Reflux 2: sodium tetrahydroborate / tetrahydrofuran; methanol / 20 °C 3: palladium on activated charcoal; hydrogen / methanol / 20 °C View Scheme
Multi-step reaction with 2 steps 1: piperidine; acetic acid / benzene / Reflux 2: lithium aluminium tetrahydride / tetrahydrofuran / Reflux View Scheme
Multi-step reaction with 2 steps 1: ammonium acetate / 1.5 h / Reflux 2: lithium aluminium tetrahydride / tetrahydrofuran / 40 h / 0 - 20 °C View Scheme
Multi-step reaction with 2 steps 1: ammonium acetate / 1.5 h / Reflux; Inert atmosphere 2: lithium aluminium tetrahydride / tetrahydrofuran / 36 h / 0 - 20 °C / Inert atmosphere View Scheme

2-iodo-4-methoxylaniline (191348-14-8) → 2-(5-methoxyindol-3-yl)ethylamine (608-07-1)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: 96 percent / 4-dimethylaminopyridine; pyridine / 14 h / 20 °C 2.1: 82 percent / triphenylphosphine; diisopropyl azodicarboxylate / tetrahydrofuran / 0 - 20 °C 3.1: tristrimethylsilylsilane; azoisobutyronitrile / toluene / 12 h / Heating 3.2: 74 percent / p-toluenesulfonic acid / toluene / 2 h / Heating 4.1: 85 percent / hydrazine monohydrate / ethanol / 3 h / Heating 5.1: 84 percent / KOH / methanol / 9 h / Heating View Scheme

N-(2-iodo-4-methoxyphenyl)methanesulfonamide (627086-06-0) → 2-(5-methoxyindol-3-yl)ethylamine (608-07-1)

Conditions

Yield

Multi-step reaction with 4 steps 1.1: 82 percent / triphenylphosphine; diisopropyl azodicarboxylate / tetrahydrofuran / 0 - 20 °C 2.1: tristrimethylsilylsilane; azoisobutyronitrile / toluene / 12 h / Heating 2.2: 74 percent / p-toluenesulfonic acid / toluene / 2 h / Heating 3.1: 85 percent / hydrazine monohydrate / ethanol / 3 h / Heating 4.1: 84 percent / KOH / methanol / 9 h / Heating View Scheme

2-[2-(1-methanesulfonyl-5-methoxy-1H-indol-3-yl)ethyl]isoindole-1,3-dione (627086-09-3) → 2-(5-methoxyindol-3-yl)ethylamine (608-07-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / hydrazine monohydrate / ethanol / 3 h / Heating 2: 84 percent / KOH / methanol / 9 h / Heating View Scheme

N-[4-(1,3-dioxodihydroisoindol-2-yl)but-2-ynyl]-N-(2'-iodo-4'-methoxyphenyl)methanesulfonamide (627086-07-1) → 2-(5-methoxyindol-3-yl)ethylamine (608-07-1)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: tristrimethylsilylsilane; azoisobutyronitrile / toluene / 12 h / Heating 1.2: 74 percent / p-toluenesulfonic acid / toluene / 2 h / Heating 2.1: 85 percent / hydrazine monohydrate / ethanol / 3 h / Heating 3.1: 84 percent / KOH / methanol / 9 h / Heating View Scheme

(5-methoxy-1H-indol-3-yl)oxoacetyl chloride (2426-19-9) → 2-(5-methoxyindol-3-yl)ethylamine (608-07-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: NH3 / dioxane / 8 h / 20 °C 2: lithium aluminum hydride / tetrahydrofuran / 8 h / Heating View Scheme
Multi-step reaction with 2 steps 1: ammonia / 1,4-dioxane / 20 °C 2: lithium aluminium tetrahydride / tetrahydrofuran / 18 h / Reflux View Scheme

1-benzyl-5-methoxy-1H-indole-3-acetamide (93879-42-6) → 2-(5-methoxyindol-3-yl)ethylamine (608-07-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 60.5 percent / LiAlH4 / diethyl ether / 48 h / Heating 2: 66 percent / Na / tetrahydrofuran; liquid ammonia / 1.5 h / -33 °C View Scheme

methyl 1-benzyl-5-methoxy-1H-indole-3-acetate (419569-93-0) → 2-(5-methoxyindol-3-yl)ethylamine (608-07-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: 83 percent / NH3 / methanol / 192 h / 20 °C 2: 60.5 percent / LiAlH4 / diethyl ether / 48 h / Heating 3: 66 percent / Na / tetrahydrofuran; liquid ammonia / 1.5 h / -33 °C View Scheme

succinic acid anhydride (108-30-5) + 2-(5-methoxyindol-3-yl)ethylamine (608-07-1) → 3-<(5-methoxy-3-indolyl)ethylamino>propionic acid (58714-14-0)

Conditions	Yield
In chloroform at 0 - 5℃; for 0.25h;	100%
In dichloromethane at 20℃; for 18h;	99%

2-(5-methoxyindol-3-yl)ethylamine (608-07-1) + acetic anhydride (108-24-7) → 5-methoxy-N-acetyl-tryptamine (73-31-4)

Conditions	Yield
With pyridine In dichloromethane	100%
In 1,2-dichloro-ethane at 0℃; for 1h;	96%
With triethylamine	95%

2-(5-methoxyindol-3-yl)ethylamine (608-07-1) + formic acid ethyl ester (109-94-4) → N-(2-(5-methoxy-1H-indol-3-yl)ethyl)formamide (104510-12-5)

Conditions	Yield
for 10h; Reflux;	100%
for 10h; Reflux;	100%
for 12h; Reflux;	100%

2-(5-methoxyindol-3-yl)ethylamine (608-07-1) + Trifluoroacetaldehyde ethyl hemiacetal (433-27-2) → 6-methoxy-1-trifluoromethyl-1,2,3,4-tetrahydro-9H-pyrido<3,4-b>indole (126260-64-8)

Conditions	Yield
at 110 - 120℃; for 5h;	99.7%

4-methyleneoxetan-2-one (674-82-8) + 2-(5-methoxyindol-3-yl)ethylamine (608-07-1) → N-<2-(5-methoxy-1H-indol-3-yl)ethyl>-3-oxobutyramide (112081-40-0)

Conditions	Yield
In tetrahydrofuran at 20℃; for 24h;	99%
In dichloromethane at 0℃; for 12.5h;

phthalic anhydride (85-44-9) + 2-(5-methoxyindol-3-yl)ethylamine (608-07-1) → 2-(2-(5-methoxy-1H-indol-3-yl)ethyl)isoindoline-1,3-dione (55747-66-5)

Conditions	Yield
With triethylamine In toluene for 24h; Reflux; Dean-Stark;	99%
at 206℃;	88%
With triethylamine In toluene for 24h; Reflux;	87%

2-(5-methoxyindol-3-yl)ethylamine (608-07-1) + di-tert-butyl dicarbonate (24424-99-5) → 3-[2-[(tert-butyloxycarbonyl)amino]ethyl]-5-methoxy-1H-indole (380358-27-0)

Conditions	Yield
With triethylamine In tetrahydrofuran at 20℃; for 12h;	99%
With triethylamine In tetrahydrofuran at 10℃; for 1h; Inert atmosphere;	99%
With triethylamine In tetrahydrofuran at 10℃; for 1h;	99%

1-methyl-1H-indole-2,3-dione (2058-74-4) + 2-(5-methoxyindol-3-yl)ethylamine (608-07-1) → (S)-6'-methoxy-1-methyl-2',3',4',9'-tetrahydrospiro[indoline-3,1'-pyrido[3,4-b]indol]-2-one (1340563-49-6)

Conditions	Yield
With (S)-3,3'-bis(2,4,6-tri-iso-propylphenyl)-1,1'-binaphthyl-2,2'-diyl hydrogenphosphate In N,N-dimethyl-formamide at 40℃; Pictet-Spengler cyclisation; Inert atmosphere; optical yield given as %ee; enantioselective reaction;	99%

2-(5-methoxyindol-3-yl)ethylamine (608-07-1) + 5-bromo-1-methyl-1H-indole-2,3-dione (2058-72-2) → 5-bromo-6'-methoxy-1-methyl-2',3',4',9'-tetrahydrospiro[indoline-3,1'-pyrido[3,4-b]indol]-2-one (904501-92-4)

Conditions	Yield
With scandium(III) chloride; sodium sulfate In dichloromethane at 23℃; Pictet-Spengler cyclisation; Inert atmosphere;	99%

3-methylbutyric acid (503-74-2) + 2-(5-methoxyindol-3-yl)ethylamine (608-07-1) → C16H22N2O2

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine at 20℃; for 18h;	99%

2-(5-methoxyindol-3-yl)ethylamine (608-07-1) + acetyl chloride (75-36-5) → 5-methoxy-N-acetyl-tryptamine (73-31-4)

Conditions	Yield
In dichloromethane at 25 - 30℃; Temperature;	98.3%
With triethylamine In dichloromethane at 20℃;
With triethylamine In dichloromethane at 0 - 20℃; for 5h;

2-(5-methoxyindol-3-yl)ethylamine (608-07-1) + 2-bromoallyl bromide (513-31-5) → 2-bromo-N-[2-(5-methoxy-1H-indol-3-yl)ethyl]prop-2-en-1-amine (1036862-81-3)

Conditions	Yield
With potassium carbonate In tetrahydrofuran at 20℃;	98%

2-(5-methoxyindol-3-yl)ethylamine (608-07-1) + 2-(2'-phenylethynyl)benzoic acid (1084-95-3) → 3-benzyl-3-hydroxy-2-(2-(5-methoxy-1H-indol-3-yl)ethyl)isoindolin-1-one (1246168-38-6)

Conditions	Yield
Stage #1: 2-(2'-phenylethynyl)benzoic acid With tetrabutylammonium acetate In water at 100℃; for 0.166667h; Microwave irradiation; Inert atmosphere; Stage #2: 2-(5-methoxyindol-3-yl)ethylamine In water at 100℃; for 0.166667h; Microwave irradiation; Inert atmosphere; regioselective reaction;	98%

2-(5-methoxyindol-3-yl)ethylamine (608-07-1) + benzaldehyde (100-52-7) → N-benzyl-2-(5-methoxy-1H-indol-3-yl)ethan-1-amine (25119-60-2)

Conditions	Yield
Stage #1: 2-(5-methoxyindol-3-yl)ethylamine; benzaldehyde In methanol at 20℃; for 36h; Stage #2: With sodium tetrahydroborate In methanol at 20℃; for 1h;	98%
Stage #1: 2-(5-methoxyindol-3-yl)ethylamine; benzaldehyde In methanol at 20℃; Stage #2: With sodium tetrahydroborate at 20℃; Borch Reduction;	98%
Stage #1: 2-(5-methoxyindol-3-yl)ethylamine; benzaldehyde In methanol at 20℃; for 36h; Stage #2: With sodium tetrahydroborate In methanol at 20℃; for 1h;
Stage #1: 2-(5-methoxyindol-3-yl)ethylamine; benzaldehyde With sodium sulfate In methanol for 12h; Stage #2: With sodium tetrahydroborate In methanol at 0℃;

2-(5-methoxyindol-3-yl)ethylamine (608-07-1) + Glyoxilic acid (298-12-4) → 6-methoxy-2,3,4,9-tetrahydro-1H-β-carboline-1-carboxylic acid (17952-63-5)

Conditions	Yield
With potassium carbonate In water; ethyl acetate at 20℃; for 24h; pH=5; Pictet-Spengler Synthesis;	98%

2-(5-methoxyindol-3-yl)ethylamine (608-07-1) + 2-((4-methoxyphenyl)ethynyl)benzoic acid (859829-95-1) → 3-hydroxy-2-(2-(5-methoxy-1H-indol-3-yl)ethyl)-3-(4-methoxybenzyl)isoindolin-1-one (1246168-42-2)

Conditions	Yield
Stage #1: 2-((4-methoxyphenyl)ethynyl)benzoic acid With tetrabutylammonium acetate In water at 100℃; for 0.166667h; Microwave irradiation; Inert atmosphere; Stage #2: 2-(5-methoxyindol-3-yl)ethylamine In water at 100℃; for 0.166667h; Microwave irradiation; Inert atmosphere; regioselective reaction;	97%

2-(5-methoxyindol-3-yl)ethylamine (608-07-1) + dimethyl 2-ketoglutarate (13192-04-6) → methyl 8-methoxy-2,3,5,6,11,11b-hexahydro-3-oxo-1H-indolizino<8,7-b>indole-11b-carboxylate (129968-05-4)

Conditions	Yield
With acetic acid for 4h; Reflux; Inert atmosphere;	97%

2-(5-methoxyindol-3-yl)ethylamine (608-07-1) + potassium thioacetate (10387-40-3) → 5-methoxy-N-acetyl-tryptamine (73-31-4)

Conditions	Yield
With tetrabutylammonium tetrafluoroborate In ethyl acetate at 20℃; Electrochemical reaction;	97%

2-(5-methoxyindol-3-yl)ethylamine (608-07-1) + n-valeryl chloride (638-29-9) → N-<2-(5-methoxy-1H-indol-3-yl)ethyl>pentanamide

Conditions	Yield
In toluene for 1h; Ambient temperature;	96%

2-(5-methoxyindol-3-yl)ethylamine (608-07-1) + 7-(trifluoromethyl)-3,4,5,6-tetrahydro-2H-azepine (1146222-77-6) → 5-(6-methoxy-1-(trifluoromethyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)pentan-1-amine

Conditions	Yield
With trifluoroacetic acid In dichloromethane at 20℃; for 168h; Pictet-Spengler Synthesis;	96%

formaldehyd (50-00-0) + 2-(5-methoxyindol-3-yl)ethylamine (608-07-1) → pinoline (20315-68-8)

Conditions	Yield
With chloro-trimethyl-silane	95%
With acetic acid In methanol at 80℃; for 1h;	83%
With sulfuric acid Erhitzen des Reaktionsprodukts mit wss. H2SO4;

2-(5-methoxyindol-3-yl)ethylamine (608-07-1) + di-tert-butyl dicarbonate (24424-99-5) + tetra(n-butyl)ammonium hydrogen sulfate + benzenesulfonyl chloride (98-09-9) + 3-[2-[(tert-butyloxycarbonyl)amino]ethyl]-5-methoxy-1H-indole (380358-27-0) → 1-(benzenesulfonyl)-3-[2-[(tert-butyloxycarbonyl)amino]ethyl]-5-methoxy-1H-indole (297751-49-6) + 2-[1-(benzenesulfonyl)-5-methoxy-1H-indol-3-yl]ethylamine hydrochloride

Conditions	Yield
With sodium hydroxide In dichloromethane	A n/a B 95%

2-(5-methoxyindol-3-yl)ethylamine (608-07-1) + 1-benzylisatin (1217-89-6) → (S)-1-benzyl-6'-methoxy-2',3',4',9'-tetrahydrospiro[indoline-3,1'-pyrido[3,4-b]indol]-2-one (1340563-51-0)

Conditions	Yield
With (S)-3,3'-bis(2,4,6-tri-iso-propylphenyl)-1,1'-binaphthyl-2,2'-diyl hydrogenphosphate In N,N-dimethyl-formamide at 40℃; Pictet-Spengler cyclisation; Inert atmosphere; optical yield given as %ee; enantioselective reaction;	95%

2-(5-methoxyindol-3-yl)ethylamine (608-07-1) + cyclohexanecarbaldehyde (2043-61-0) → 1-cyclohexyl-6-methoxy-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole

Conditions	Yield
With trifluoroacetic acid In dichloromethane at 20℃; Pictet-Spengler Synthesis;	95%

2-(5-methoxyindol-3-yl)ethylamine (608-07-1) + 4-Nitrobenzenesulfonyl chloride (98-74-8) → N-(2-(5-methoxy-1H-indol-3-yl)ethyl)-4-nitrobenzenesulfonamide

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃; Inert atmosphere; Schlenk technique;	95%

2-(5-methoxyindol-3-yl)ethylamine (608-07-1) + (4-fluorophenyl)glyoxal (403-32-7) → (4-fluorophenyl)(6-methoxy-9H-pyrido[3,4-b]indol-1-yl)methanone (1148028-92-5)

Conditions	Yield
Stage #1: 2-(5-methoxyindol-3-yl)ethylamine; (4-fluorophenyl)glyoxal In dichloromethane Stage #2: With montmorillonite K-10; palladium 10% on activated carbon In methanol; dichloromethane for 0.0833333h; Pictet-Spengler cyclisation; Stage #3: at 130℃; for 0.116667h; Microwave irradiation;	94%
With 5%-palladium/activated carbon; montmorillonite K10 Clay at 130℃; Microwave irradiation;

2-(5-methoxyindol-3-yl)ethylamine (608-07-1) + levulinic acid (123-76-2) → 8-Methoxy-2,3,5,6,11,11b-hexahydro-3-oxo-11b-methyl-1H-indolizino<8,7-b>indole (734-15-6)

Conditions	Yield
at 180℃; under 11251.1 Torr; for 0.0333333h; Pictet-Spengler condensation; Microwave irradiation; Neat (no solvent);	94%

Upstream product

• 1006-94-6 5-methoxylindole 
• 917-64-6 methyl magnesium iodide 
• 60-29-7 diethyl ether 
• 107-14-2 chloroacetonitrile 
• 70351-49-4 (5-methoxy-2-oxo-2,3-dihydro-1H-indol-3-yl)acetonitrile 
• 52648-13-2 5-methoxytryptamine-2-carboxylic acid 
• 68935-49-9 5-methoxy-3-(2-nitroethyl)-1H-indole 
• 3471-32-7 4-Methoxyphenylhydrazine 
• 102016-76-2 N-(2-(5-methoxy-1H-indol-3-yl)ethyl)-4-methylbenzenesulfonamide 
• 40619-73-6 2-(1-benzyl-5-methoxy-1H-indol-3-yl)ethylamine 
• 55747-60-9 5-methoxy-3-(2-phthalimido-ethyl)-indole-2-carboxylic acid 
• 712-09-4 5-methoxytryptophol 
• 153-98-0 serotonin hydrochloride 
• 1210-83-9 N-acetyl-5-hydroxytryptamine 

Downstream Products

• 20315-68-8 pinoline 
• 102016-76-2 N-(2-(5-methoxy-1H-indol-3-yl)ethyl)-4-methylbenzenesulfonamide 
• 6582-72-5 5-Methoxy-N,N-dimethyltryptamin-methiodid 
• 50-67-9 3-(2-aminoethyl)-1H-indol-5-ol 
• 55747-66-5 2-[2-(5-methoxy-1H-indol-3-yl)-ethyl]-isoindole-1,3-dione 
• 75671-07-7 N-<2-(5-methoxy-3-indolyl)ethyl>-2-chloro-2-phenylacetamide 
• 66012-83-7 N-Butyryl-5-methoxytryptamine 
• 122576-90-3 5-methoxy-3-<2-(diphenylmethanimino)-ethyl>-indole 
• 36933-22-9 L-N-Z-γ-methyl-N-<2-(5-methoxy-3-indolyl)ethyl>isoglutamide 
• 174727-69-6 2-[1-(2,5-Dimethyl-benzyl)-5-methoxy-1H-indol-3-yl]-ethylamine 
• 104724-19-8 (E)-N-[2-(5-Methoxy-1H-indol-3-yl)-ethyl]-2-methyl-3-phenyl-acrylamide 
• 107292-74-0 1,2,3,4-Tetrahydro-5-<<2-(1H-indol-3-yl)ethyl>amino>-1-(phenylmethyl)-4-pyridinecarboxylic acid, ethyl ester 
• 29573-13-5 1-benzyl-1,2,3,4-tetrahydro-8-methoxy-β-carboline-1-carboxylic acid 
• 104724-21-2 (E)-3-(3-Chloro-phenyl)-N-[2-(5-methoxy-1H-indol-3-yl)-ethyl]-acrylamide 

Relevant articles and documents

Synthesis, pulse radiolysis, and in vitro radioprotection studies of melatoninolipoamide, a novel conjugate of melatonin and α-lipoic acid

A novel conjugate of melatonin 2 and α-lipoic acid 4 has been prepared using DCC mediated coupling. The conjugate named melatoninolipoamide has been assigned its structure 1 on the basis of spectral analysis (UV, IR, NMR, and EI-MS). Pulse radiolysis studies of the conjugate were carried out in aqueous solutions with both oxidizing and reducing radicals. The results indicate that the melatonin moiety of the conjugate reacts preferably with oxidizing radicals and the lipoic acid moiety exhibits preferential reaction with reducing radicals. The in vitro radioprotection ability of 1 was examined by γ-radiation induced lipid peroxidation in liposomes and hemolysis of erythrocytes, and compared the results with those of melatonin and α-lipoic acid. The studies suggest that the conjugate can be explored as a probable radioprotector.

Design, Synthesis, and Biological Activity of Hydrogen Peroxide Responsive Arylboronate Melatonin Hybrids

Stimulus-responsive cleavage reactions have found broad use to direct drug release at a particular target disease area. Increased levels of reactive oxygen species (ROS) have been associated with the development and progression of cancer and several other disease states, motivating the development of drug conjugates that can undergo a chemoselective ROS-triggered release. Melatonin (MLT) and the reactive electrophile p-benzoquinone methide (p-QM) have evidenced either cytoprotective or cytotoxic effects in biological systems, depending on the dose, cellular targets, and time of exposure. In this study, we report the synthesis and biological activity of two MLT derivatives linked to ROS-responsive arylboronate triggers (P1 and P2), which can be activated by endogenously generated hydrogen peroxide (H2O2) to release MLT, or 5-methoxytryptamine (5-MeOT), and p-QM-intermediates. Their H2O2-induced activation mechanism was studied by HPLC-DAD-MS. P1, which rapidly releases MLT and p-QM, was able to strongly induce the Nrf2 antioxidant signaling pathway, but was ineffective to provide protection against H2O2-mediated oxidative damage. By contrast, P1 exhibited strong toxic effects in HeLa cancer cells, without causing significant toxicity to normal NCTC-2544 cells. Similar, although more limited, effects were exerted by P2. In both cases, cytotoxicity was accompanied by depletion of cellular glutathione (GSH), probably as a consequence of p-QM release, and increased ROS levels. A role for MLT in toxicity was also observed, suggesting that the P1 released products, MLT and p-QM, contributed additively to promote cell death.

Method for synthesizing melatonin intermediate by taking methoxyphenamine as raw material

The invention belongs to the technical field of compound synthesis, and aims to solve the problem that expensive reducing agents are needed in the present method for synthesizing melatonin, and the cost is high. The invention provides a method for synthesizing melatonin intermediate by taking methoxyphenamine as a raw material, and the like. Pt / Al with supported catalyst by taking methoxyaniline and ethylene glycol as raw materials2 O3 One-step hydrothermal method synthesizes 5 - methoxyindole and then obtains melatonin precursor 3 methoxytryptamine by 5 -step hydrothermal reaction. 5 - Methoxyindole is firstly synthesized by taking ethylene glycol and paramethoxyaniline as raw materials, then 3 methoxytryptamine is obtained through 5 - steps, and the total yield of the reaction is 14.0%. final synthesis of melatonin. A new melatonin synthesis route is designed, and the melatonin precursor 5 - methoxytryptamine is synthesized by using a raw material aniline derivative and ethylene glycol which are simple in application structure and low in cost.

Synthesis method of melatonin

The invention discloses a synthesis method of melatonin, and belongs to the technical field of pharmaceutical chemistry synthesis. According to the method, 5-hydroxytryptamine hydrochloride is used as a raw material, 5-methoxytryptamine is obtained through a methylation reaction of hydroxyl through a one-pot feeding method, a crude melatonin product is prepared through an acetylation reaction of amino, and finally, the finished melatonin is obtained through one-step refining and purification. The melatonin synthesis method provided by the invention avoids waste caused by step-by-step purification of the product, and has the characteristics of short synthesis route, short synthesis period, few raw material types and the like, the obtained product is high in yield, and the purity can meet the market demand. The synthesis method of the melatonin provided by the invention saves the cost and is easy for industrial production.