Browse Prior Art Database

Crystalline forms of intermediates of 6-(3-Chloro-2-fluorobenzyl)-1-[1(S)-(hydroxymethyl)-2-methylpropyl]-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

IP.com Disclosure Number: IPCOM000236005D
Publication Date: 2014-Apr-02
Document File: 7 page(s) / 157K

Publishing Venue

The IP.com Prior Art Database

This text was extracted from a PDF file.
This is the abbreviated version, containing approximately 44% of the total text.

Page 01 of 7

    Crystalline forms of intermediates of 6-(3-Chloro-2-fluorobenzyl)-1-[1(S)- (hydroxymethyl)-2-methylpropyl]-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

 

     6-(3-Chloro-2-fluorobenzyl)-1-[1(S)-(hydroxymethyl)-2-methylpropyl]-7-methoxy-4- oxo-1,4-dihydroquinoline-3-carboxylic acid referred to as Compound I, has the following chemical structure:

 

  (S)-ethyl 2-(5-bromo-2,4-dimethoxybenzoyl)-3-(1-hydroxy-3-methylbutan-2- ylamino)-acrylate referred to as Compound II is an intermediate in the preparation of Compound I. Samples of Compound II were prepared by the process described in example 1, and were analyzed by X-ray powder diffraction ("XRPD") to provide a crystalline form. Figure 1 presents the XRPD of the obtained form.

Figure 1: XRPD of crystalline Compound II 

14000

Intensity (counts)

12000

10000

8000

6000

4000

2000

0


Page 02 of 7

    According to figure 1, the crystalline form of Compound II is characterized by XRPD peaks at: 10.2, 11.1, 13.4, 14.2, 15.8, 16.3, 17.5, 18.7, 20.0, 20.5, 21.3, 21.8, 22.9, 23.8, 25.5,
26.0, 27.4, 29.5 and 32.3 °2theta ± 0.2 °2theta.

Figure 2: FTIR spectrum of crystalline Compound II 

90

85

80

75

70

65

%T

60

55

50

45

40

3000

2000

1500

1000

500

Wavenumbers (cm-1)

(S)-ethyl 2-(5-bromo-2,4-dimethoxybenzoyl)-3-(1-(tert-butyldimethylsilyloxy)-3- methylbutan-2-ylamino)acrylate referred to as Compound III is another intermediate in the preparation of Compound I. Samples of Compound III were prepared by the process described in example 2, and were analyzed by XRPD to provide a crystalline form. Figure 3 presents the XRPD of the obtained form.


Page 03 of 7

Figure 3: XRPD of crystalline Compound III

Intensity (counts)

6000

5000

4000

3000

2000

1000

0

5

10 15 20 25 30 35 2Theta (°)

According to figure 3, the crystalline form of Compound III is characterized by XRPD peaks at: 8.5, 11.2, 14.6, 15.1, 16.3, 16.7, 16.9, 17.6, 18.5, 19.7, 21.0, 21.9, 22.5, 23.7, 24.8, 27.9,
29.6 and 33.2 °2theta ± 0.2 °2theta.

Figure 4: FTIR spectrum of crystalline Compound III

75

70

65

60

55

50

%T

45

40

35

30

25

20

15

3000

2000

1500

1000

500

Wavenumbers (cm-1)

 


Page 04 of 7

(S)-ethyl 6-bromo-1-(1-(tert-butyldimethylsilyloxy)-3-methylbutan-2-yl)-7-methoxy- 4-oxo-1,4-dihydroquinoline-3-carboxylate referred to as Compound IV is another intermediate in the preparation of Compound I. Samples of Compound IV were prepared by the process described in examples 3 and 4, and were analyzed by XRPD to provide a two crystalline forms. Figure 5 presents the XRPD of form I obtained according to example 3. 
 

Figure 5: XRPD of crystalline form I of Compound IV

Intensity (counts)

10000

6400

3600

1600

400

0

5 10 15 20 25 30 35 2Theta (°)

    According to figure 5, crystalline form I of Compound IV is characterized by XRPD peaks at: 8.8, 9.7, 10.6, 13.4, 11.9, 12.4, 13.7, 14.8, 15.8, 17.6, 18.9, 19.6, 20.4, 21.2, 22.7,
24.5 and 26.6 °2theta ± 0.2 °2theta.

Figure 6: FTIR of crystalline form I of Compound IV

90

85

80

75

70

%T

65

60

55

5...