The Prior Art Database and Publishing service will be updated on Sunday, February 25th, from 1-3pm ET. You may experience brief service interruptions during that time.
Browse Prior Art Database

Triethylenetetramine Hydrochloride Morph

IP.com Disclosure Number: IPCOM000249361D
Publication Date: 2017-Feb-21
Document File: 8 page(s) / 903K

Publishing Venue

The IP.com Prior Art Database


A process for preparation of Form T of the dihydrochloride salt of Triethylenetetramine or N,N'-bis(2-aminoethyl)-1,2-ethanediamine is described. Form T is characterised by X-ray diifraction spectra, Infra-red spectra, Differential scanning calorimetry (DSC) and melting point.

This text was extracted from a Microsoft Word document.
At least one non-text object (such as an image or picture) has been suppressed.
This is the abbreviated version, containing approximately 51% of the total text.

Triethylenetetramine Hydrochloride Morph


Triethylenetetramine or N, N’-bis(2-aminoethyl)-1,2-ethanediamine belongs to the class of polyethylene polyamines and is used as a chelating agent for removing copper in the body.

Triethylenetetramine dihydrochloride:Compound (1)                                                          

US 8067641 disclose Form I and Form II of compound (1), characterized by melting point, differential scanning colorimetry (DSC) and infra-red spectra (IR).

Scheme-1: Synthesis of N, N’-bis(2-aminoethyl)-1,2-ethanediamine dihydrochloride (1)

The process disclosed herein (Scheme1) relates to a new polymorph Form T which is characterized by X-ray powder diffraction spectra (XRPD), IR spectra, melting point and DSC.


Example 1:   Preparation of 2-([2-[cyanomethyl)t-butyloxycarbonylamino]ethyl-t-butyloxy carbonylamino)acetonitrile (5):

Potassium carbonate (481 g) was added to the stirred mixture of ethylene diamine (100 g) and acetonitrile (100 ml), cooled to around 100C, followed by gradual addition of chloroacetonitrile (263.2 g) at the same temperature. The reaction mass was stirred at 25-300C, till completion of the reaction, as monitored by HPLC. After completion, the mixture was cooled and Boc-anhydride (760 g) was added to it, followed by stirring at the same temperature till completion of the reaction, as monitored by HPLC.

The reaction mass was filtered and the filtrate was concentrated. Addition of toluene to the residue, heating the mixture to around 700C, followed by cooling of the mass, stirring and filtration provided 2-([2-[cyanomethyl)-t-butyloxycarbonylamino]ethyl-t-butyloxycarbonylamino)acetonitrile (5).  Yield:   507 g (90 %)

Example 2:   Preparation of t-butyl (N-2-aminoethyl)N-([2-[(2-aminoethyl)-t-butyloxy)carbonylamino]ethyl)carbamate (6):

Raney nickel (120 g) in isopropanol (100 ml) was charged into an autoclave, followed by addition of compound 5 (200 g) in isopropanol (400 ml). Cooled ammonia solution (W/W 9% ammonia in isopropanol) was charged into the autoclave and the reaction was carried out at around 300C under hydrogen pressure of 5 Kg/cm2. The reaction was monitored by HPLC.

After completion of the reaction, the mass was filtered, concentrated, and methyl tertiary butyl ether was added to the residue. The mixture was heated to around 500C, followed by cooling of the mass, stirring, optional seeding with compound 6 and filtration to give tertiary butyl(N-2-aminoethyl)-N-([2-[(2-aminoethyl)-(tert-butyloxy)carbonylamino] ethyl)carbamate. Yield:  174 g (85 %)

Example 3:   Preparation of N,N’-bis(2-aminoethyl)-1,2-ethanediamine dihydrochloride (1)

Concentrated hydrochloric acid (121.5 g) was gradually added to a stirred mixture of tertiarybutyl-N-(2-aminoethyl)-N-2-[(2-aminoethyl)-(tert-butoxy)carbonyl]amino] ethyl}carbamate  (Compoun...