143388-64-1

Basic information

• Product Name: NARATRIPTAN HYDROCHLORIDE (125 MG)F0C3600.998MG/MG(AI)
• Synonyms: NARATRIPTAN HYDROCHLORIDE (125 MG)F0C3600.998MG/MG(AI);Amerge.;Naramig;Naratriptan Hydrochloride;N-Methyl-2-[3-(1-methyl-4-piperidyl)-1H-indol-5-yl]-ethanesulfonamide Hydrochloride;N-Methyl-3-(1-methylpiperidin-4-yl)-1H-indole-5-ethanesulfonamide hydrochloride;Naratriptan monohydrochloride;Naratriptan Hydrochloride (125 mg)
• CAS NO: 143388-64-1
• Molecular Formula: C₁₇H₂₅N₃O₂S*ClH
• Molecular Weight: 371.93
• Product Categories: Intermediates & Fine Chemicals;Pharmaceuticals;APIs;Amerge, Naramig;Inhibitors
• Mol File: 143388-64-1.mol
• Article Data: 8

Chemical Properties

• Melting Point: 234-236°C
• Boiling Point: 541.3 °C at760mmHg
• Flash Point: 281.2 °C
• Appearance: white to off-white/
• Vapor Pressure: 8.81E-12mmHg at 25°C
• Storage Temp.: -20°C Freezer
• Solubility: H2O: ≥10mg/mL
• CAS DataBase Reference: NARATRIPTAN HYDROCHLORIDE (125 MG)F0C3600.998MG/MG(AI)(CAS DataBase Reference)
• NIST Chemistry Reference: NARATRIPTAN HYDROCHLORIDE (125 MG)F0C3600.998MG/MG(AI)(143388-64-1)
• EPA Substance Registry System: NARATRIPTAN HYDROCHLORIDE (125 MG)F0C3600.998MG/MG(AI)(143388-64-1)

Safety Data

• Hazard Codes: Xi
• Statements: 36
• Safety Statements: 26
• WGK Germany: 3
• Hazardous Substances Data: 143388-64-1(Hazardous Substances Data)

Usage

Description

Naramig was launched in Germany, Sweden and the UK for use in migraine. It is chemically available via a number of related synthetic routes all having about three steps starting from 5-bromoindole. It is a new serotonin 5-HT1B/1D receptor antagonist with modest affinity for 5-HT1a, and very weak affinity for 5-HT3 receptors. It has little or no affinity for a wide range of non-serotonin receptors including a- and padrenoceptors, dopamine, neurokinin NK1, and opiate receptors. It mediates vasoconstriction in cerebral vasculature (extra cerebral intracranial vessels), reduces neurogenic inflammation, and inhibits responses mediated by the trigeminal nerves. It has a 6- and 3-fold greater affinity for 5-HT1B, and 5-HT1D, receptors, respectively, than sumatriptan which translates to a 2-3 fold increase in potency. The reoccurance of headache was less compared to sumatriptan, zolmitriptan and rizatriptan. Naramig had no clinical effects on blood pressure or heart rate, had a long duration of action with very good tolerability, and has high oral bioavailability.

Chemical Properties

Beige Solid

Uses

Different sources of media describe the Uses of 143388-64-1 differently. You can refer to the following data:
1. Naratriptan Hydrochloride is a triptan drug and is used for the treatment of migraine headaches
2. Naratriptan Hydrochloride is a triptan drug that is used for the treatment of migraine headaches. It is a selective 5-hydroxytryptamine1 receptor subtype agonist
3. laxative

InChI:InChI=1/C17H25N3O2S.ClH/c1-18-23(21,22)10-7-13-3-4-17-15(11-13)16(12-19-17)14-5-8-20(2)9-6-14;/h3-4,11-12,14,18-19H,5-10H2,1-2H3;1H

Synthetic route

naratriptan (121679-13-8) → naratriptan hydrochloride (143388-64-1)

Conditions	Yield
With hydrogenchloride In ethanol at 0 - 30℃; for 1h; pH=1.0 - 1.5; Product distribution / selectivity;	93.4%
With hydrogenchloride In methanol; water at 0 - 10℃;	84%
With hydrogenchloride In methanol; ethanol at 5 - 25℃; pH=1.0;	71.7%
With hydrogenchloride In isopropyl alcohol; acetone at 5 - 10℃; pH=1;

palladium oxide on charcoal + N-methyl-2-[3-(1,2,3,6-tetrahydro-1-methyl-4-pyridinyl)-1H-indol-5-yl]ethenesulphonamide (166306-28-1) → naratriptan hydrochloride (143388-64-1)

Conditions	Yield
In hydrogenchloride; methanesulfonic acid; water	88%
With hydrogenchloride In water; ethyl acetate; N,N-dimethyl-formamide
With hydrogenchloride In water; ethyl acetate; N,N-dimethyl-formamide

N-methyl-2-[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indol-5-yl]ethanesulfonamide (121679-20-7) → naratriptan hydrochloride (143388-64-1)

Conditions	Yield
Stage #1: N-methyl-2-[3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indol-5-yl]ethanesulfonamide With hydrogen; acetic acid; platinum(IV) oxide In methanol at 50 - 60℃; under 3677.86 Torr; Stage #2: With hydrogenchloride In ethanol; isopropyl alcohol for 1h; Product distribution / selectivity; Reflux;	85%
Multi-step reaction with 2 steps 1.1: hydrogen; acetic acid / palladium 10% on activated carbon / 25 °C / 1448.05 - 2172.08 Torr 1.2: 10 °C / pH 7.5 - 8.5 2.1: hydrogenchloride / isopropyl alcohol; acetone / 5 - 10 °C / pH 1 View Scheme

palladium oxide on charcoal + (E)-N-Methyl-2-[3-(1,2,3,6-tetrahydro-1-methyl-4-pyridinyl)-1H-indol-5-yl]ethene sulphonamide, hydrochloride (166306-29-2) → naratriptan hydrochloride (143388-64-1)

Conditions	Yield
In methanol; water; ethyl acetate; N,N-dimethyl-formamide	71.2%

C18H24N3O4S(1-)*Na(1+) → naratriptan hydrochloride (143388-64-1)

Conditions	Yield
With hydrogenchloride In water for 12h; pH=2; Product distribution / selectivity; Heating / reflux;

palladium oxide on charcoal + N-methyl-2-[3-(1,2,3,6-tetrahydro-1-methyl-4-pyridinyl)-1H-indol-5-yl]ethenesulphonamide (166306-28-1) + pyrographite (7440-44-0) → naratriptan hydrochloride (143388-64-1)

Conditions	Yield
With hydrogenchloride In ethyl acetate; N,N-dimethyl-formamide
With hydrogenchloride In ethyl acetate; N,N-dimethyl-formamide

2-(4-amino-phenyl)ethanesulfonic acid methylamide (98623-16-6) → naratriptan hydrochloride (143388-64-1)

Conditions	Yield
Multi-step reaction with 8 steps 1.1: sodium hydrogencarbonate; iodine / dichloromethane / 25 - 30 °C 2.1: dichloromethane / 1.5 h / 25 °C 3.1: copper(l) iodide; lithium chloride / N,N-dimethyl-formamide / 0.5 h / 25 °C 3.2: 25 °C 4.1: potassium hydroxide; ethanol / 15 - 25 °C 5.1: potassium tert-butylate / 1-methyl-pyrrolidin-2-one / 80 - 85 °C 5.2: 0.5 h / 25 °C 6.1: trifluoroacetic acid / ethanol / 25 °C / Reflux 6.2: 10 - 15 °C / pH 8 7.1: hydrogen; acetic acid / palladium 10% on activated carbon / 25 °C / 1448.05 - 2172.08 Torr 7.2: 10 °C / pH 7.5 - 8.5 8.1: hydrogenchloride / isopropyl alcohol; acetone / 5 - 10 °C / pH 1 View Scheme
Multi-step reaction with 7 steps 1.1: sodium hydrogencarbonate; iodine / dichloromethane / 25 - 30 °C 2.1: dichloromethane / 1.5 h / 25 °C 3.1: copper(l) iodide; lithium chloride / N,N-dimethyl-formamide / 0.5 h / 25 °C 3.2: 25 °C 4.1: potassium tert-butylate / 1-methyl-pyrrolidin-2-one / 25 - 85 °C / Inert atmosphere 4.2: 0.5 h / 25 °C 5.1: trifluoroacetic acid / ethanol / 25 °C / Reflux 5.2: 10 - 15 °C / pH 8 6.1: hydrogen; acetic acid / palladium 10% on activated carbon / 25 °C / 1448.05 - 2172.08 Torr 6.2: 10 °C / pH 7.5 - 8.5 7.1: hydrogenchloride / isopropyl alcohol; acetone / 5 - 10 °C / pH 1 View Scheme
Multi-step reaction with 8 steps 1.1: sodium hydrogencarbonate; iodine / dichloromethane / 25 - 30 °C 2.1: methanol / 25 - 30 °C 2.2: 4 h / 25 - 30 °C 3.1: copper(l) iodide; lithium chloride / N,N-dimethyl-formamide / 0.5 h / 25 °C 3.2: 25 °C 4.1: potassium hydroxide; ethanol / 15 - 25 °C 5.1: potassium tert-butylate / 1-methyl-pyrrolidin-2-one / 80 - 85 °C 6.1: potassium hydroxide / methanol / 8 h / 60 - 65 °C 7.1: hydrogen; ethanol; triethylsilane / palladium 10% on activated carbon / ethanol / 25 - 30 °C 8.1: hydrogenchloride / isopropyl alcohol; acetone / 5 - 10 °C / pH 1 View Scheme
Multi-step reaction with 9 steps 1.1: sodium hydrogencarbonate; iodine / dichloromethane / 25 - 30 °C 2.1: methanol / 25 - 30 °C 2.2: 4 h / 25 - 30 °C 3.1: copper(l) iodide; lithium chloride / N,N-dimethyl-formamide / 0.5 h / 25 °C 3.2: 25 °C 4.1: potassium hydroxide; ethanol / 15 - 25 °C 5.1: potassium tert-butylate / 1-methyl-pyrrolidin-2-one / 80 - 85 °C 6.1: potassium hydroxide / methanol / 8 h / 60 - 65 °C 7.1: trifluoroacetic acid / dichloromethane / 0.17 h / 25 °C 7.2: 25 - 30 °C 7.3: 10 - 15 °C 8.1: hydrogen; acetic acid / palladium 10% on activated carbon / 25 °C / 724.03 Torr 8.2: 10 °C / pH 7.5 - 8.5 9.1: hydrogenchloride / isopropyl alcohol; acetone / 5 - 10 °C / pH 1 View Scheme

N-Methyl-1H-indole-5-ethanesulphonamide (98623-50-8) → naratriptan hydrochloride (143388-64-1)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: trifluoroacetic acid / ethanol / 25 °C / Reflux 1.2: 10 - 15 °C / pH 8 2.1: hydrogen; acetic acid / palladium 10% on activated carbon / 25 °C / 1448.05 - 2172.08 Torr 2.2: 10 °C / pH 7.5 - 8.5 3.1: hydrogenchloride / isopropyl alcohol; acetone / 5 - 10 °C / pH 1 View Scheme

N-[2-iodo-4-(2-(methylsulfamoyl)ethyl)phenyl]acetamide (1268265-90-2) → naratriptan hydrochloride (143388-64-1)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: copper(l) iodide; lithium chloride / N,N-dimethyl-formamide / 0.5 h / 25 °C 1.2: 25 °C 2.1: potassium hydroxide; ethanol / 15 - 25 °C 3.1: potassium tert-butylate / 1-methyl-pyrrolidin-2-one / 80 - 85 °C 3.2: 0.5 h / 25 °C 4.1: trifluoroacetic acid / ethanol / 25 °C / Reflux 4.2: 10 - 15 °C / pH 8 5.1: hydrogen; acetic acid / palladium 10% on activated carbon / 25 °C / 1448.05 - 2172.08 Torr 5.2: 10 °C / pH 7.5 - 8.5 6.1: hydrogenchloride / isopropyl alcohol; acetone / 5 - 10 °C / pH 1 View Scheme
Multi-step reaction with 5 steps 1.1: copper(l) iodide; lithium chloride / N,N-dimethyl-formamide / 0.5 h / 25 °C 1.2: 25 °C 2.1: potassium tert-butylate / 1-methyl-pyrrolidin-2-one / 25 - 85 °C / Inert atmosphere 2.2: 0.5 h / 25 °C 3.1: trifluoroacetic acid / ethanol / 25 °C / Reflux 3.2: 10 - 15 °C / pH 8 4.1: hydrogen; acetic acid / palladium 10% on activated carbon / 25 °C / 1448.05 - 2172.08 Torr 4.2: 10 °C / pH 7.5 - 8.5 5.1: hydrogenchloride / isopropyl alcohol; acetone / 5 - 10 °C / pH 1 View Scheme

2-(4-benzylamino-3-iodophenyl)ethanesulfonic acid methylamide (1268265-93-5) → naratriptan hydrochloride (143388-64-1)

Conditions	Yield
Multi-step reaction with 7 steps 1.1: copper(l) iodide; lithium chloride / N,N-dimethyl-formamide / 0.5 h / 25 °C 1.2: 25 °C 2.1: potassium hydroxide; ethanol / 15 - 25 °C 3.1: potassium tert-butylate / 1-methyl-pyrrolidin-2-one / 80 - 85 °C 4.1: potassium hydroxide / methanol / 8 h / 60 - 65 °C 5.1: trifluoroacetic acid / dichloromethane / 0.17 h / 25 °C 5.2: 25 - 30 °C 5.3: 10 - 15 °C 6.1: hydrogen; acetic acid / palladium 10% on activated carbon / 25 °C / 724.03 Torr 6.2: 10 °C / pH 7.5 - 8.5 7.1: hydrogenchloride / isopropyl alcohol; acetone / 5 - 10 °C / pH 1 View Scheme
Multi-step reaction with 6 steps 1.1: copper(l) iodide; lithium chloride / N,N-dimethyl-formamide / 0.5 h / 25 °C 1.2: 25 °C 2.1: potassium hydroxide; ethanol / 15 - 25 °C 3.1: potassium tert-butylate / 1-methyl-pyrrolidin-2-one / 80 - 85 °C 4.1: potassium hydroxide / methanol / 8 h / 60 - 65 °C 5.1: hydrogen; ethanol; triethylsilane / palladium 10% on activated carbon / ethanol / 25 - 30 °C 6.1: hydrogenchloride / isopropyl alcohol; acetone / 5 - 10 °C / pH 1 View Scheme

N-[4-(2-{methylsulfamoyl}ethyl)-2-{2-(trimethylsilanyl)ethynyl}phenyl]acetamide (1268265-95-7) → naratriptan hydrochloride (143388-64-1)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: potassium hydroxide; ethanol / 15 - 25 °C 2.1: potassium tert-butylate / 1-methyl-pyrrolidin-2-one / 80 - 85 °C 2.2: 0.5 h / 25 °C 3.1: trifluoroacetic acid / ethanol / 25 °C / Reflux 3.2: 10 - 15 °C / pH 8 4.1: hydrogen; acetic acid / palladium 10% on activated carbon / 25 °C / 1448.05 - 2172.08 Torr 4.2: 10 °C / pH 7.5 - 8.5 5.1: hydrogenchloride / isopropyl alcohol; acetone / 5 - 10 °C / pH 1 View Scheme
Multi-step reaction with 4 steps 1.1: potassium tert-butylate / 1-methyl-pyrrolidin-2-one / 25 - 85 °C / Inert atmosphere 1.2: 0.5 h / 25 °C 2.1: trifluoroacetic acid / ethanol / 25 °C / Reflux 2.2: 10 - 15 °C / pH 8 3.1: hydrogen; acetic acid / palladium 10% on activated carbon / 25 °C / 1448.05 - 2172.08 Torr 3.2: 10 °C / pH 7.5 - 8.5 4.1: hydrogenchloride / isopropyl alcohol; acetone / 5 - 10 °C / pH 1 View Scheme

2-(4-benzylamino-3-trimethylsilanylethynyl-phenyl)ethanesulfonic acid methylamide (1268265-97-9) → naratriptan hydrochloride (143388-64-1)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: potassium hydroxide; ethanol / 15 - 25 °C 2.1: potassium tert-butylate / 1-methyl-pyrrolidin-2-one / 80 - 85 °C 3.1: potassium hydroxide / methanol / 8 h / 60 - 65 °C 4.1: trifluoroacetic acid / dichloromethane / 0.17 h / 25 °C 4.2: 25 - 30 °C 4.3: 10 - 15 °C 5.1: hydrogen; acetic acid / palladium 10% on activated carbon / 25 °C / 724.03 Torr 5.2: 10 °C / pH 7.5 - 8.5 6.1: hydrogenchloride / isopropyl alcohol; acetone / 5 - 10 °C / pH 1 View Scheme
Multi-step reaction with 5 steps 1: potassium hydroxide; ethanol / 15 - 25 °C 2: potassium tert-butylate / 1-methyl-pyrrolidin-2-one / 80 - 85 °C 3: potassium hydroxide / methanol / 8 h / 60 - 65 °C 4: hydrogen; ethanol; triethylsilane / palladium 10% on activated carbon / ethanol / 25 - 30 °C 5: hydrogenchloride / isopropyl alcohol; acetone / 5 - 10 °C / pH 1 View Scheme

N-[2-ethynyl-4-(2-(methylsulfamoyl)ethyl)phenyl]acetamide (1268265-99-1) → naratriptan hydrochloride (143388-64-1)

Conditions

Yield

Multi-step reaction with 4 steps 1.1: potassium tert-butylate / 1-methyl-pyrrolidin-2-one / 80 - 85 °C 1.2: 0.5 h / 25 °C 2.1: trifluoroacetic acid / ethanol / 25 °C / Reflux 2.2: 10 - 15 °C / pH 8 3.1: hydrogen; acetic acid / palladium 10% on activated carbon / 25 °C / 1448.05 - 2172.08 Torr 3.2: 10 °C / pH 7.5 - 8.5 4.1: hydrogenchloride / isopropyl alcohol; acetone / 5 - 10 °C / pH 1 View Scheme

2-(4-benzylamino-3-ethynylphenyl)ethanesulfonic acid methylamide (1268266-01-8) → naratriptan hydrochloride (143388-64-1)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: potassium tert-butylate / 1-methyl-pyrrolidin-2-one / 80 - 85 °C 2.1: potassium hydroxide / methanol / 8 h / 60 - 65 °C 3.1: trifluoroacetic acid / dichloromethane / 0.17 h / 25 °C 3.2: 25 - 30 °C 3.3: 10 - 15 °C 4.1: hydrogen; acetic acid / palladium 10% on activated carbon / 25 °C / 724.03 Torr 4.2: 10 °C / pH 7.5 - 8.5 5.1: hydrogenchloride / isopropyl alcohol; acetone / 5 - 10 °C / pH 1 View Scheme
Multi-step reaction with 4 steps 1: potassium tert-butylate / 1-methyl-pyrrolidin-2-one / 80 - 85 °C 2: potassium hydroxide / methanol / 8 h / 60 - 65 °C 3: hydrogen; ethanol; triethylsilane / palladium 10% on activated carbon / ethanol / 25 - 30 °C 4: hydrogenchloride / isopropyl alcohol; acetone / 5 - 10 °C / pH 1 View Scheme

2-(1-benzyl-1H-indol-5-yl)ethanesulfonic acid methylamide (894351-85-0) → naratriptan hydrochloride (143388-64-1)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: potassium hydroxide / methanol / 8 h / 60 - 65 °C 2.1: trifluoroacetic acid / dichloromethane / 0.17 h / 25 °C 2.2: 25 - 30 °C 2.3: 10 - 15 °C 3.1: hydrogen; acetic acid / palladium 10% on activated carbon / 25 °C / 724.03 Torr 3.2: 10 °C / pH 7.5 - 8.5 4.1: hydrogenchloride / isopropyl alcohol; acetone / 5 - 10 °C / pH 1 View Scheme
Multi-step reaction with 3 steps 1: potassium hydroxide / methanol / 8 h / 60 - 65 °C 2: hydrogen; ethanol; triethylsilane / palladium 10% on activated carbon / ethanol / 25 - 30 °C 3: hydrogenchloride / isopropyl alcohol; acetone / 5 - 10 °C / pH 1 View Scheme

2-[1-benzyl-3-(1-methyl-1,2,3,6-tetrahydro-pyridin-4-yl)-1H-indol-5-yl]-ethanesulfonic acid methylamide (894351-86-1) → naratriptan hydrochloride (143388-64-1)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: trifluoroacetic acid / dichloromethane / 0.17 h / 25 °C 1.2: 25 - 30 °C 1.3: 10 - 15 °C 2.1: hydrogen; acetic acid / palladium 10% on activated carbon / 25 °C / 724.03 Torr 2.2: 10 °C / pH 7.5 - 8.5 3.1: hydrogenchloride / isopropyl alcohol; acetone / 5 - 10 °C / pH 1 View Scheme

N-methyl-2-[1-benzyl-3-(1-methylpiperidin-4-yl)-1H-indol-5-yl]ethanesulfonamide (894351-87-2) → naratriptan hydrochloride (143388-64-1)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: hydrogen; acetic acid / palladium 10% on activated carbon / 25 °C / 724.03 Torr 1.2: 10 °C / pH 7.5 - 8.5 2.1: hydrogenchloride / isopropyl alcohol; acetone / 5 - 10 °C / pH 1 View Scheme

2-(4-amino-3-iodo-phenyl)ethanesulfonic acid methylamide (1200070-42-3) → naratriptan hydrochloride (143388-64-1)

Conditions	Yield
Multi-step reaction with 7 steps 1.1: dichloromethane / 1.5 h / 25 °C 2.1: copper(l) iodide; lithium chloride / N,N-dimethyl-formamide / 0.5 h / 25 °C 2.2: 25 °C 3.1: potassium hydroxide; ethanol / 15 - 25 °C 4.1: potassium tert-butylate / 1-methyl-pyrrolidin-2-one / 80 - 85 °C 4.2: 0.5 h / 25 °C 5.1: trifluoroacetic acid / ethanol / 25 °C / Reflux 5.2: 10 - 15 °C / pH 8 6.1: hydrogen; acetic acid / palladium 10% on activated carbon / 25 °C / 1448.05 - 2172.08 Torr 6.2: 10 °C / pH 7.5 - 8.5 7.1: hydrogenchloride / isopropyl alcohol; acetone / 5 - 10 °C / pH 1 View Scheme
Multi-step reaction with 6 steps 1.1: dichloromethane / 1.5 h / 25 °C 2.1: copper(l) iodide; lithium chloride / N,N-dimethyl-formamide / 0.5 h / 25 °C 2.2: 25 °C 3.1: potassium tert-butylate / 1-methyl-pyrrolidin-2-one / 25 - 85 °C / Inert atmosphere 3.2: 0.5 h / 25 °C 4.1: trifluoroacetic acid / ethanol / 25 °C / Reflux 4.2: 10 - 15 °C / pH 8 5.1: hydrogen; acetic acid / palladium 10% on activated carbon / 25 °C / 1448.05 - 2172.08 Torr 5.2: 10 °C / pH 7.5 - 8.5 6.1: hydrogenchloride / isopropyl alcohol; acetone / 5 - 10 °C / pH 1 View Scheme
Multi-step reaction with 7 steps 1.1: methanol / 25 - 30 °C 1.2: 4 h / 25 - 30 °C 2.1: copper(l) iodide; lithium chloride / N,N-dimethyl-formamide / 0.5 h / 25 °C 2.2: 25 °C 3.1: potassium hydroxide; ethanol / 15 - 25 °C 4.1: potassium tert-butylate / 1-methyl-pyrrolidin-2-one / 80 - 85 °C 5.1: potassium hydroxide / methanol / 8 h / 60 - 65 °C 6.1: hydrogen; ethanol; triethylsilane / palladium 10% on activated carbon / ethanol / 25 - 30 °C 7.1: hydrogenchloride / isopropyl alcohol; acetone / 5 - 10 °C / pH 1 View Scheme
Multi-step reaction with 8 steps 1.1: methanol / 25 - 30 °C 1.2: 4 h / 25 - 30 °C 2.1: copper(l) iodide; lithium chloride / N,N-dimethyl-formamide / 0.5 h / 25 °C 2.2: 25 °C 3.1: potassium hydroxide; ethanol / 15 - 25 °C 4.1: potassium tert-butylate / 1-methyl-pyrrolidin-2-one / 80 - 85 °C 5.1: potassium hydroxide / methanol / 8 h / 60 - 65 °C 6.1: trifluoroacetic acid / dichloromethane / 0.17 h / 25 °C 6.2: 25 - 30 °C 6.3: 10 - 15 °C 7.1: hydrogen; acetic acid / palladium 10% on activated carbon / 25 °C / 724.03 Torr 7.2: 10 °C / pH 7.5 - 8.5 8.1: hydrogenchloride / isopropyl alcohol; acetone / 5 - 10 °C / pH 1 View Scheme

naratriptan hydrochloride (143388-64-1) → 2-[4-formylamino-3-(1-methylpiperidine-4-carbonyl)phenyl]ethanesulphonic acid methylamide

Conditions	Yield
With sodium periodate In methanol at 20℃; for 68.5h;	76%

1-((4-azido)phenylthio)pyrrolidine-2,5-dione + naratriptan hydrochloride (143388-64-1) → 2-(2-(4-azidophenyl)thio-3-(1-methylpiperidin-4-yl)-1H-indol-5-yl)-N-methylethanesulfonamide

Conditions	Yield
With 2-((-2-(3-(3,5-bis(trifluoromethyl)phenyl)thioureido)cyclohexyl)carbamoyl)-3,4,5,6-tetrachlorobenzoic acid; trifluoroacetic acid In methanol; dichloromethane; water at 20℃; for 24h;	49%

naratriptan hydrochloride (143388-64-1) → 1-methyl-5'-(2-(N-methylsulfamoyl)ethyl)-2'-oxo-1-azaspiro[bicyclo[2.2.1]heptane-7,3'-indolin]-1-ium iodide

Conditions	Yield
With water; iodine; sodium hydrogencarbonate In tetrahydrofuran at 20℃; for 20h; chemoselective reaction;	24%

naratriptan hydrochloride (143388-64-1) → naratriptan (121679-13-8)

Conditions	Yield
With sodium hydroxide In water

Upstream product

• 166306-28-1 N-methyl-2-[3-(1,2,3,6-tetrahydro-1-methyl-4-pyridinyl)-1H-indol-5-yl]ethenesulphonamide 
• 166306-29-2 (E)-N-Methyl-2-[3-(1,2,3,6-tetrahydro-1-methyl-4-pyridinyl)-1H-indol-5-yl]ethene sulphonamide, hydrochloride 
• 121679-20-7 N-methyl-2-(3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indol-5-yl)ethane-1-sulfonamide 
• 1200070-42-3 2-(4-amino-3-iodo-phenyl)ethanesulfonic acid methylamide 
• 894351-87-2 N-methyl-2-[1-benzyl-3-(1-methylpiperidin-4-yl)-1H-indol-5-yl]ethanesulfonamide 
• 894351-86-1 2-[1-benzyl-3-(1-methyl-1,2,3,6-tetrahydro-pyridin-4-yl)-1H-indol-5-yl]-ethanesulfonic acid methylamide 
• 894351-85-0 2-(1-benzyl-1H-indol-5-yl)ethanesulfonic acid methylamide 
• 1268266-01-8 2-(4-benzylamino-3-ethynylphenyl)ethanesulfonic acid methylamide 
• 1268265-99-1 N-[2-ethynyl-4-(2-(methylsulfamoyl)ethyl)phenyl]acetamide 
• 1268265-97-9 2-(4-benzylamino-3-trimethylsilanylethynyl-phenyl)ethanesulfonic acid methylamide 
• 1268265-95-7 N-[4-(2-{methylsulfamoyl}ethyl)-2-{2-(trimethylsilanyl)ethynyl}phenyl]acetamide 
• 1268265-93-5 2-(4-benzylamino-3-iodophenyl)ethanesulfonic acid methylamide 
• 1268265-90-2 N-[2-iodo-4-(2-(methylsulfamoyl)ethyl)phenyl]acetamide 
• 98623-50-8 N-Methyl-1H-indole-5-ethanesulphonamide 

Downstream Products

• 121679-13-8 naratriptan 

Relevant articles and documents

A PROCESS FOR THE SYNTHESIS OF NARATRIPTAN

The present invention relates to a process for preparing naratriptan or a salt thereof, the process comprising: (a) reacting a compound of formula (3) with a compound of the formula HCCR wherein Z is a protecting group, Y is a leaving group and R is a trialkyl silyl group, a trialkylstannyl group or a zinc (II) halide, to obtain the compound of formula (4); (b) converting the compound of formula (4) to a compound of formula (5) wherein Z'' is hydrogen or a benzyl group; (c) converting the compound of formula (5) to naratriptan; and (d) optionally converting naratriptan to a salt thereof. The present invention also provides novel compounds (3) and (4) and processes for their preparation.

PROCESS FOR PREPARATION OF NARATRIPTAN HYDROCHLORIDE

The present invention relates to an improved process for the preparation of N-methyl-3- (1-methyl-4-piperidinyl)-1H-indole-5-ethanesulfonamide hydrochloride of formula (I) having less than 0.15 % area by HPLC of 3-(1-methyl-4-piperidinyl)-1H-indole-5- ethanesulfonamide (1A) and intermediates thereof.

PROCESS FOR THE PREPARATION OF INDOLE DERIVATIVES

The present invention relates to a novel process for the preparation of indole derivatives. In particular, present invention relates to the process for preparing naratriptan of formula (I), and its salts using novel intermediates. The present invention also relates to novel synthetic intermediates useful in the preparation of naratriptan hydrochloride.