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A crystalline form of N-(2,4-difluorobenzyl)-4-(benzyloxy)-3-oxobutanamide

IP.com Disclosure Number: IPCOM000237227D
Publication Date: 2014-Jun-09
Document File: 2 page(s) / 30K

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 2

A crystalline form of N-(2,4-difluorobenzyl)-4-(benzyloxy)-3-oxobutanamide

    Provided herein is a process for preparing crystalline N-(2,4-difluorobenzyl)-4-(benzyloxy)- 3-oxobutanamide, referred herein as Compound I. The process is described in Example 1.

    The isolated samples of Compound I were analyzed by X-ray powder diffraction ("XRPD"), which indicated a formation of a crystalline form of Compound I. Figure 1 depicts the XRPD of the obtained crystalline form. Compound I may be used for preparing (4R,12aS)-9-((2,4-difluorobenzyl)- carbamoyl)-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2Hpyrido[1',2':4,5]pyrazino[2,1-
b][1,3]oxazin-7-olate and salts thereof.

XRPD method

    The analysis was performed on ARL (SCINTAG) X-Ray powder diffractometer model X'TRA equipped with a solid state detector. Copper radiation of 1.5418 Å was used. Scanning parameters: range: 2-40 degrees two-theta; scan mode: continuous scan; step size: 0.05°, and a rate of 3 deg/min.

Figure 1: XRPD Diffractogram of Compound I

degrees 2-theta

    
According to Figure 1, the crystalline form of Compound I is characterized by XRPD peaks at: 6.8, 7.3, 10.8, 13.6, 14.6, 16.5, 18.1, 20.4, 21.8 and 22.8 degrees 2-theta ± 0.2 degrees 2-theta.


Page 02 of 2

Example 1: A process for preparing Compound I

Step A: Ethyl 4-(benzyloxy)-3-oxobutanoate (15 g) was dissolved in toluene (150 ml) followed by addition of ethylene glycol (24 ml) and p-toluenesulfonic acid (PTSA) (0.97 g). To the reaction vessel was connected Dean-Stark distillation system and the reaction mixture was refluxed till full consumption of the starting material. The reaction was cooled to RT, washed with aqueous K...