Browse Prior Art Database

Salts of 4-[3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy]-7-methoxy-6-quinolinecarboxamide

IP.com Disclosure Number: IPCOM000248423D
Publication Date: 2016-Nov-27
Document File: 6 page(s) / 307K

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 6

Salts of 4-[3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy]-7- methoxy-6-quinolinecarboxamide

4-[3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy]-7-methoxy-6- quinolinecarboxamide has the following chemical structure (referred to herein as Compound I):

N

O

 H3CO H2N

O

NH O

NH

Cl

(I)

Compound - I

Provided are processes for preparing and crystallizing compound I as Oxalate salt, compound I as 1,5-dinapsylate salt, compound I as Besylate salt, compound I as Phosphate salt and compound I as Ethane-1,2-disulphonate salt.

Powder X-ray Diffraction (XRPD) method

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

PANalytical X'Pert Pro; CuKα radiation (λ = 1.54 Å); PIXcel 1D detector; Back-loading Sample Holder. Prior to analysis, the sample was adjusted into a cavity of the sample holder ring and the surface of the sample was smoothed by means of a press block and holder ring was locked in holder base.

Measurement parameters:

Scan range: 3 - 50 degrees 2-theta; Scan mode: continuous;


Page 02 of 6

Step size: 0.0065652 degrees;

Time per step: 20.4 s;

Sample spin: 1 s;

Sample holder: Back-loading Sample Holder. Example-1: Preparation of compound I Oxalate salt

To a solution of Compound I (5g) in methanol (75ml) oxalic acid (1.6 g) was added at 60 °C over a period of 10-15 minutes. When the reaction mass becomes viscous further methanol (20ml) was added to it. The reaction mass was cooled to 20-30 °C and stirred at this temperature for 1 to 2 hours at this temperature. The reaction mass was filtered and washed with methanol (5ml). After drying 5.6g (92.5%) product was obtained.

The obtained product was analyzed by XRPD and the obtained PXRD pattern is presented in Figure 1


Page 03 of 6

Figure 1: XRPD pattern of Compound I Oxalate salt

Main XRPD peaks of compound I Oxalate salt are .9, 9.4, 11.0, 14.2, 15.8, 18.1, 29.5,
22.3, 25.1 and 26.5 degrees two theta ±0.2 degrees two theta

Example-2: Preparation of compound I 1,5-dinapsylate salt

To a solution of Compound I (2g) in methanol (20ml) Naphthalene-1,5-disulphonic acid tetrahydrate (1.8g) was added at 60 °C over a period of 10-15 minutes. The reaction mass was cooled to 20-30 °C and stirred at this temperature for 30 minutes. The reaction mass was filtered and washed with methanol (5ml). After drying 2.3g (85.8 %) product was obtained

The obtained crystalline product was analyzed by XRPD and the obtained PXRD pattern is presented in Figure 2


Page 04 of 6

   Figure 2: XRPD pattern of crystalline form of Compound I 1,5-dinapsylate salt Main XRPD peaks of the crystalline compound I...