Browse Prior Art Database

SOLID STATE FORM OF INTERMEDIATE IN PREPARATION OF (1 S, 2S, 3R,5S)-3- [7-[(1R,2S)-2-(3,4-DIFLUOROPHENYL)CYCLOPROPYLAMINO]-5-(PROPYLTHIO)- 3H-[1,2,3]TRIAZOLO[4,5-D]PYRIMIDIN-3-Y1]-5-(2-HYDROXYETHOXY) CYCLOPENTANE-1 ,2-DIOL

IP.com Disclosure Number: IPCOM000237912D
Publication Date: 2014-Jul-21
Document File: 4 page(s) / 107K

Publishing Venue

The IP.com Prior Art Database

This text was extracted from a PDF file.
This is the abbreviated version, containing approximately 52% of the total text.

Page 01 of 4

SOLID STATE FORM OF INTERMEDIATE IN PREPARATION OF (1 S, 2S, 3R,5S)-3- [7-[(1R,2S)-2-(3,4-DIFLUOROPHENYL)CYCLOPROPYLAMINO]-5-(PROPYLTHIO)- 3H-[1,2,3]TRIAZOLO[4,5-D]PYRIMIDIN-3-Y1]-5-(2-HYDROXYETHOXY) CYCLOPENTANE-1 ,2-DIOL

(1 S, 2S, 3R, 5S)-3-[7-[(1R,2S)-2-(3,4-Difluorophenyl)cyclopropylamino]-5-

(propylthio)- 3H-[1,2, 3]triazolo[4,5-d]pyrimidin-3-y1]-5-(2-hydroxyethoxy)cyclopentane-1 ,2-

diol (referred to as "Compound 1"), has the following chemical structure:

Compound 1

    (1R, 2S)-2-(3, 4-difluorophenyl) cyclopropan-1-amine hydrochloride (referred to as Compound 2), is an intermediate in the preparation of Compound 1.

Compound 2 has the following chemical structure:

Compound 2

    A sample of Compound 2 was prepared by the process described in the below example, and was analyzed by X-ray powder diffraction ("XRPD") to provide a crystalline form. Figure 1 represents the XRPD of the obtained form.

1


Page 02 of 4

Figure 1: XRPD pattern of crystalline form of Compound 2

Main PXRD peaks:


5.5; 11.1; 12.2; 15.5; 16.7; 17.7; 18.2; 18.7; 20.8; 21.2; 22.1; 22.9; 23.5; 24.1; 24.7; 25.4; 26.7; 28.3;
29.0; 29.6; 31.3; 31.6; 32.6; 33.0; 33.8; 34.3; 34.7; 36.0; 36.2; 36.9; 38.0; 38.8; 39.2 and 39.6 degrees two theta ± 0.2 degrees 2-theta

Powder X-ray Diffraction (XRD) method

X-ray diffraction was performed on X-Ray powder diffractometer:


Bruker D8 Advance; CuK_ radiation (λ = 1.5418 Å); Lynx eye detector; laboratory temperature 22- 25 °C; PMMA specimen holder ring. Prior to analysis, the samples were gently ground by means of mortar and pestle in order to obtain a fine powder. The ground sample was adjusted into a cavity of the sample holder and the surface of the sample was smoothed by means of a cover glass. Measurement parameters:

Scan range: 2 - 40 degrees 2-theta;

Scan mode: continuous;

Step size: 0.05 degrees;

Time per step: 0.5 s;

2


Page 03 of 4

Sample spin: 30 rpm;

Sample holder: PMMA specimen holder ring. Divergence slit: V20

Example

Example 1: Procedure for the preparation of (1R, 2S)-2-(3, 4-difluorophenyl)cyclopropan-1-amine

hydrochloride.

To the solution of EthylChloroFormate in toluene, (1R, 2R)-2-(3, 4-difluorophenyl) cyclopropane-1- carboxylic acid +Tri ethyl amine solution in toluene was added drop wise in to it by maintaining the internal temperature -10 to -5°C in a period of 60-90mins. The reaction mass was stirred for at least 30 minute after completion of addition and monitored the reaction on HPLC. After completion of reaction sodium azide solution in water was added in to it under stirring at -10 to 5°C in 15-30 minutes. The reaction was stirred at 0-5°C and monitored on HPLC. After completion of reaction layer was separated out and washed it with water. The organic layer...