1053239-39-6

Basic information

• Product Name: 2-(1,6,7,8-Tetrahydro-2H-indeno[5,4-b]furan-8-yl)ethylaMine hydrochloride
• Synonyms: 2-(1,6,7,8-Tetrahydro-2H-indeno[5,4-b]furan-8-yl)ethylaMine hydrochloride;1,6,7,8-Tetrahydro-2H-indeno[5,4-b]furan-8-ethanamine hydrochloride;2H-Indeno[5,4-b]furan-8-ethanaMine, 1,6,7,8-tetrahydro- (hydrochloride)(1:1);2-(2,6,7,8-Tetrahydro-1H-indeno[5,4-b]furan-8-yl)ethanamine hydrochloride;2-(1,6,7,8-Tetrahydro-2H-indeno[5,4-b]furan-8-yl)ethanamine hydro chloride (1:1)
• CAS NO: 1053239-39-6
• Molecular Formula: C₁₃H₁₇NO*ClH
• Molecular Weight: 239.74112
• Mol File: 1053239-39-6.mol
• Article Data: 5

Chemical Properties

• Melting Point: 165-167℃
• Appearance: /
• Density: 1.058±0.06 g/cm3 (20ºC 760 Torr)
• CAS DataBase Reference: 2-(1,6,7,8-Tetrahydro-2H-indeno[5,4-b]furan-8-yl)ethylaMine hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: 2-(1,6,7,8-Tetrahydro-2H-indeno[5,4-b]furan-8-yl)ethylaMine hydrochloride(1053239-39-6)
• EPA Substance Registry System: 2-(1,6,7,8-Tetrahydro-2H-indeno[5,4-b]furan-8-yl)ethylaMine hydrochloride(1053239-39-6)

Safety Data

• Hazardous Substances Data: 1053239-39-6(Hazardous Substances Data)

Usage

General Description

2-(1,6,7,8-Tetrahydro-2H-indeno[5,4-b]furan-8-yl)ethylamine hydrochloride, also known as THIIC, is a chemical compound that belongs to the class of organic compounds known as phenyls. It is a psychoactive drug and a selective serotonin releasing agent. THIIC acts on the central nervous system, producing effects such as increased heart rate, euphoria, and enhanced sensory perception. It is often used recreationally for its stimulating and hallucinogenic properties. However, it also has potential therapeutic uses in the treatment of mood disorders and anxiety. THIIC is typically found in the form of a white powder and is commonly administered orally, intravenously, or through inhalation.

Synthetic route

2-(1,2,6,7-tetrahydro-8H-indeno[5,4-b]furan-8-ylidene)acetonitrile (221530-44-5) → 2‑(1,6,7,8‑tetrahydro‑2H‑indeno[5,4‑b]furan‑8‑yl)ethylamine hydrochloride (1053239-39-6)

Conditions	Yield
With hydrogen; platinum(IV) chloride In methanol; chloroform at 30 - 40℃; under 2250.23 - 3750.38 Torr; for 2h; Solvent; Reagent/catalyst;	97%
Multi-step reaction with 2 steps 1: sodium tetrahydroborate / ethanol / 2 h / Large scale 2: hydrogenchloride / water; methanol / 1 h / 45 °C / Large scale View Scheme

(2E)-2-(4,5-dibromo-1,2,6,7-tetrahydro-8H-indeno[5,4-b]furan-8-ylidene)ethanamine hydrochloride → 2‑(1,6,7,8‑tetrahydro‑2H‑indeno[5,4‑b]furan‑8‑yl)ethylamine hydrochloride (1053239-39-6)

Conditions	Yield
Stage #1: (2E)-2-(4,5-dibromo-1,2,6,7-tetrahydro-8H-indeno[5,4-b]furan-8-ylidene)ethanamine hydrochloride With sodium carbonate In water; toluene Stage #2: With hydrogen; sodium acetate; palladium 10% on activated carbon In methanol; toluene at 50℃; under 3310.08 Torr; Stage #3: With hydrogenchloride In isopropyl alcohol; toluene at 30℃; for 2h; pH=2;	87%

C13H15NO2 (1053239-38-5) → 2‑(1,6,7,8‑tetrahydro‑2H‑indeno[5,4‑b]furan‑8‑yl)ethylamine hydrochloride (1053239-39-6)

Conditions	Yield
Stage #1: C13H15NO2 With sodium tetrahydroborate; boron trifluoride diethyl etherate In tetrahydrofuran at 25 - 35℃; for 24 - 25h; Stage #2: With hydrogenchloride In water; ethyl acetate

2-(1,6,7,8-tetrahydro-2H-indeno[5,4-b]furan-8-ylidene)ethylamine hydrochloride → 2‑(1,6,7,8‑tetrahydro‑2H‑indeno[5,4‑b]furan‑8‑yl)ethylamine hydrochloride (1053239-39-6)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol; water at 20℃;

1,2,6,7-tetrahydro-8H-indeno[5,4-b]-furan-8-one (196597-78-1) → 2‑(1,6,7,8‑tetrahydro‑2H‑indeno[5,4‑b]furan‑8‑yl)ethylamine hydrochloride (1053239-39-6)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium hydride / tetrahydrofuran / 1 h / 25 °C / Large scale 1.2: 3.5 h / Large scale 2.1: sodium tetrahydroborate / ethanol / 2 h / Large scale 3.1: hydrogenchloride / water; methanol / 1 h / 45 °C / Large scale View Scheme

N-tert-butoxycarbonyl-1,2,6,7-tetrahydro-8H-indeno[5,4-b]furan-8-ylethylamine → 2‑(1,6,7,8‑tetrahydro‑2H‑indeno[5,4‑b]furan‑8‑yl)ethylamine hydrochloride (1053239-39-6)

Conditions	Yield
With hydrogenchloride In methanol; water at 45℃; for 1h; Large scale;	4.1 kg

2‑(1,6,7,8‑tetrahydro‑2H‑indeno[5,4‑b]furan‑8‑yl)ethylamine hydrochloride (1053239-39-6) + propionic acid anhydride (123-62-6) → N-(2-(1,6,7,8-tetrahydro-2H-indeno[5,4-b]furan-8-yl)ethyl)propionamide

Conditions	Yield
With sodium hydrogencarbonate In water at 5 - 10℃; for 1h; pH=5.5;	86%

2‑(1,6,7,8‑tetrahydro‑2H‑indeno[5,4‑b]furan‑8‑yl)ethylamine hydrochloride (1053239-39-6) + propionyl chloride (79-03-8) → N-(2-(1,6,7,8-tetrahydro-2H-indeno[5,4-b]furan-8-yl)ethyl)propionamide

Conditions	Yield
Stage #1: 2‑(1,6,7,8‑tetrahydro‑2H‑indeno[5,4‑b]furan‑8‑yl)ethylamine hydrochloride With sodium hydroxide In tetrahydrofuran at 5 - 10℃; for 0.5h; pH=13 - 13.5; Stage #2: propionyl chloride In tetrahydrofuran at 5℃; pH=5.5 - 6.0;	75%
With triethylamine In tetrahydrofuran at 10 - 35℃; for 2 - 3h;

2‑(1,6,7,8‑tetrahydro‑2H‑indeno[5,4‑b]furan‑8‑yl)ethylamine hydrochloride (1053239-39-6) + butyryl chloride (141-75-3) → N-[2-(1,6,7,8-tetrahydro-2H-indeno[5,4-b]furan-8-yl)ethyl]butyramide

Conditions	Yield
	67%
With sodium hydroxide In water	67%

2‑(1,6,7,8‑tetrahydro‑2H‑indeno[5,4‑b]furan‑8‑yl)ethylamine hydrochloride (1053239-39-6) + (-)-O,O′-dibenzoyl-L-tartaric acid monohydrate (62708-56-9) → (S)-2-(1,6,7,8-tetrahydro-2H-indeno[5,4-b]furan-8-yl)ethylamine dibenzoyl-L-tartaric acid

Conditions	Yield
Stage #1: 2‑(1,6,7,8‑tetrahydro‑2H‑indeno[5,4‑b]furan‑8‑yl)ethylamine hydrochloride With sodium hydroxide In dichloromethane; water Stage #2: (-)-O,O′-dibenzoyl-L-tartaric acid monohydrate In acetonitrile at 60℃;

2‑(1,6,7,8‑tetrahydro‑2H‑indeno[5,4‑b]furan‑8‑yl)ethylamine hydrochloride (1053239-39-6) → 2‑(1,6,7,8‑tetrahydro‑2H‑indeno[5,4‑b]furan‑8‑yl)‑1‑ethylamine (448964-37-2)

Conditions	Yield
With palladium on activated charcoal; hydrogen In methanol at 60℃; under 750.075 Torr; for 1h; Pressure; Temperature; Large scale;	3.2 kg

2‑(1,6,7,8‑tetrahydro‑2H‑indeno[5,4‑b]furan‑8‑yl)ethylamine hydrochloride (1053239-39-6) → (S)-2-(2,6,7,8-tetrahydro-2H-indeno[5,4-b]furan-8-yl)ethylamine S-ibuprofen salt

Conditions	Yield
Multi-step reaction with 2 steps 1: palladium on activated charcoal; hydrogen / methanol / 1 h / 60 °C / 750.08 Torr / Large scale 2: methanol / 1 h / 55 - 60 °C / Large scale View Scheme

2‑(1,6,7,8‑tetrahydro‑2H‑indeno[5,4‑b]furan‑8‑yl)ethylamine hydrochloride (1053239-39-6) → ramelteon (196597-26-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: palladium on activated charcoal; hydrogen / methanol / 1 h / 60 °C / 750.08 Torr / Large scale 2.1: methanol / 1 h / 55 - 60 °C / Large scale 3.1: sodium hydroxide / tetrahydrofuran; water / 0.08 h / Large scale 3.2: 2 h / 10 °C / Large scale View Scheme

Upstream product

• 1053239-38-5 C₁₃H₁₅NO₂ 
• 196597-78-1 1,2,6,7-tetrahydro-8H-indeno[5,4-b]-furan-8-one 
• 221530-44-5 2-(1,2,6,7-tetrahydro-8H-indeno[5,4-b]furan-8-ylidene)acetonitrile 

Downstream Products

• 196597-27-0 N-[2-(1,6,7,8-tetrahydro-2H-indeno[5,4-b]furan-8-yl)ethyl]propionamide 
• 448964-37-2 2?(1,6,7,8?tetrahydro?2H?indeno[5,4?b]furan?8?yl)?1?ethylamine 
• 196597-26-9 ramelteon 

Relevant articles and documents

Preparation method of ramelteon intermediate

The invention discloses a method for preparing a ramelteon intermediate 2-(1, 6, 7, 8-tetrahydro-2H-indeno[5,4-b]furan-8-yl) ethylamine hydrochloride with a structure as shown in a formula I which isdescribed in the specification. The method specifically comprises the following steps: by taking 2-(1, 2, 6, 7-tetrahydro-8H-indeno[5,4-b] furan-8-subunit)acetonitrile (II) as a raw material, generating a chemical content I by adopting a hydrogenation one-step method under the conditions of a certain temperature, a catalyst and a solvent. The preparation method provided by the invention is simpleand convenient to operate, and avoids the following defects of the traditional method: (1) reaction conditions are harsh; (2) the reaction time is too long, and the intermediate state III is incompletely converted; and (3), a large amount of polymerization impurities A and B are generated in the reaction process, and the reaction conversion rate is low. Existing synthetic routes and impurities A and B are shown in the specification.

A lightning-US for amine method for the preparation of (by machine translation)

The invention relates to a preparation method of Ramelteon. The method mainly comprises three reaction steps of hydrogenation, chiral resolution and acylation reaction. According to the synthesis of the Ramelteon, 2-(1,6,7,8-tetralin-2H-indeno[5,4-b]furan-8-subunit) ethylamine hydrochloride serves as a start raw material, Pd-C serves as a catalyst, and 2-(1,6,7,8-tetralin-2H-indeno[5,4-b]furan-8-base) ethylamine hydrochloride, namely an midbody-1, is acquired through catalytic hydrogenation; chiral resolution is conducted on the midbody-1 through dibenzoyl-L-tartrate, so that (S)-2-(1,6,7,8-tetralin-2H-indeno[5,4-b]furan-8-base) ethylamine dibenzoyl-L-tartrate, namely a midbody-2, is acquired; an acylation reaction is conducted on the midbody-2 and propionyl chloride, so that a crude product of the Ramelteon is acquired, and a finished product of the Ramelteon is acquired after the crude product is refined and qualified.

INTERMEDIATES AND PROCESSES FOR THE SYNTHESIS OF RAMELTEON

Provided are intermediates Formulae (IV), (V), (VI), (VII), (IX) and processes for preparation of Ramelteon, wherein X = O-Alkyl or -NH2.