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SOLID STATE FORMS OF (R)-6-HYDROXY-8-{1-HYDROXY-2-[2-(4-METHOXYPHENYL)-1,1-DIMETHYLETHYLAMINO]ETHYL}-4H-BENZO[1,4]OXAZIN-3-ONE HYDROCHLORIDE

IP.com Disclosure Number: IPCOM000248477D
Publication Date: 2016-Dec-06

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The IP.com Prior Art Database

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Page 01 of 11

SOLID STATE FORMS OF (R)-6-HYDROXY-8-{1-HYDROXY-2-[2-(4- METHOXYPHENYL)-1,1-DIMETHYLETHYLAMINO]ETHYL}-4H- BENZO[1,4]OXAZIN-3-ONE HYDROCHLORIDE

    Described herein are solid state forms of (R)‐6‐hydroxy‐8‐{1‐hydroxy‐2‐[2‐(4‐ methoxyphenyl)‐1,1‐dimethylethylamino]ethyl}‐4H‐benzo[1,4]oxazin‐3‐one hydrochloride, referred herein as compound A.

Samples of the solid state forms of Compound A were prepared according to the

processes described in examples 1 to 8 below, and were analyzed by X-ray powder diffraction

("XRPD"). Figures 1-8 present the XRPD, of the obtained forms I-VII and amorphous form

of Compound A.

Figure 1: XRPD pattern of crystalline form I of Compound A:

The crystalline form I of Compound A is characterized by XRPD peaks as provided in the table below (± 0.2 deg. 2θ). Form I of Compound A may be an anhydrous form.

Pos. [°2θ]

Intensity (cps)

400

300

200

100

0

5 10 15 20 25 30 35 40 2Theta (°)

d-spacing


[Å]

Rel. Int. [%]
5.3 16.82 100.0
6.8 12.97 9.3
8.2 10.81 3.2
9.5 9.29 2.3


10.1 8.79 20.9
10.5 8.44 15.2
11.0 8.02 2.4
11.5 7.72 3.3
12.1 7.34 5.5
12.2 7.24 10.4
12.6 7.04 20.3

12.8 6.89 7.7
13.6 6.50 25.2
13.9 6.36 3.2
14.5 6.09 16.6
15.2 5.82 10.3
15.5 5.72 37.1
15.6 5.67 35.7
16.0 5.54 3.2
16.4 5.42 13.1
17.0 5.23 12.7
17.2 5.16 15.1
17.5 5.06 7.5


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18.3 4.84 20.7
18.5 4.79 19.9
19.1 4.65 11.7
19.5 4.55 12.5
20.0 4.44 7.0
20.2 4.40 5.5
20.5 4.33 10.9
20.9 4.25 11.7
21.1 4.21 7.3
21.6 4.11 13.2
22.1 4.02 23.3
22.4 3.97 16.4
22.8 3.90 5.8
23.0 3.86 22.5
23.5 3.79 13.6
23.6 3.78 15.4
24.2 3.68 1.6
24.7 3.61 28.6
25.3 3.52 25.2
25.8 3.45 12.7
26.5 3.37 17.2
26.9 3.32 3.0

27.4 3.25 3.4
27.8 3.21 9.6
28.1 3.17 4.1
28.6 3.12 4.0
29.9 2.99 13.4
30.5 2.93 4.4
30.7 2.91 2.4
31.3 2.86 2.0
31.8 2.81 7.6
32.2 2.78 4.5
32.7 2.74 10.0
33.1 2.71 10.3
34.0 2.64 2.4
34.9 2.57 1.0
35.5 2.53 6.7
36.8 2.44 6.4
38.0 2.37 4.3
38.5 2.34 3.2
38.9 2.31 2.3
39.4 2.29 2.3

Figure 2: XRPD pattern of crystalline form II of Compound A:

Intensity (cps)

700

600

500

400

300

200

100

0

5 10 15 20 25 30 35 40 2Theta (°)


Page 03 of 11

The crystalline form II of Compound A is characterized by XRPD peaks as provided in the table below (± 0.2 deg. 2θ). Form II of Compound A is an IPA solvate.

Pos. [°2θ]

Rel. Int. [%]
6.6 13.43 71.2
9.6 9.18 11.3
9.9 8.91 16.8


13.1 6.75 36.9
13.3 6.66 26.3
13.6 6.49 6.2
14.5 6.11 5.2
14.8 5.99 2.5
15.0 5.89 8.4
15.7 5.64 9.0
16.1 5.51 16.4
17.5 5.07 4.6
18.6 4.78 65.4
19.1 4.65 15.0
19.3 4.61 15.6
19.5 4.54 28.1
19.8 4.48 16.4
20.8 4.28 3.8
21.2 4.19 5.4
21.8 4.08 12.0
22.5 3.95 8.5
22.9 3.89 7.6
23.0 3.86 8.8
23.2 3.83 8.3
23.8 3.74 4.9
24.1 3.69 100.0
24.3 3.66 37.7
24.7 3.61 7.3
25.1 3.54 15.4
25.2 3.53 12.1
25.7 3.46 12.2
26.3 3.38 10.1
26.8 3.32 4.8
27.4 3.25 14.6

27.6 3.23 16.7
27.7 3.21 9.6
28.1 3.17 5.2
28.3 3.15 13.8
28.8 3.10 10.1
29.1 3.06 4.5
29.6 3.02 2.2
30.1 2.97 9.4
30.3 2.95 6.1
30.7 2.91 1.2
31.3 2.85 12.3
31.4 2.85 14.2
31.6 2.83 7.7
32.0 2.80 3.1
32.6 2.75 4.2
32.8 2.73 2.7
33.1 2.71 1.0
33.9 2.64 4.5
34.2 2.62 6.3
34.4 2.60 8.8
34.5 2.60 6.8
34.9 2.57 4.0
35.3 2.54 1.7
35....