NOVEL CRYSTALLINE FORMS OF (S)-7-OXA-2-AZA-SPIRO[4.5]DECANE-2-CARBOXYLIC ACID [7-(3,6-DIHYDRO-2H-PYRAN-4-YL)-4-METHOXY-THIAZOLO[4,5-C]PYRIDIN-2-YL]-AMIDE AND CO-CRYSTAL FORMS THEREOF
A process prepares novel crystalline forms of (S)-7-oxa-2-aza-spiro[4.5]decane-2-carboxylic acid [7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-thiazolo[4,5-c]pyridin-2-yl]-amide. The crystalline forms find application in medicaments and pharmaceutical preparations.
1 . A crystalline form of (S)-7-oxa-2-aza-spiro[4,5]decane-2-carboxylic acid [7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-thiazolo[4,5-c]pyridin-2-yl]-amide.
2 . The crystalline form of (S)-7-oxa-2-aza-spiro[4,5]decane-2-carboxylic acid [7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-thiazolo[4,5-c]pyridin-2-yl]-amide according to claim 1 , wherein the
crystalline form is a crystalline anhydrous form A1.
3 . The crystalline form of (S)-7-oxa-2-aza-spiro[4,5]decane-2-carboxylic acid [7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-thiazolo[4,5-c]pyridin-2-yl]-amide according to claim 1 , wherein the
crystalline form is selected from the group consisting of the hydrate forms NF2, NF3, NF4 and NF12.
4 . The crystalline form of (S)-7-oxa-2-aza-spiro[4,5]decane-2-carboxylic acid [7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-thiazolo[4,5-c]pyridin-2-yl-amide according to claim 1 , wherein the
crystalline form is a co-crystal form selected from the group consisting of
a) a mono fumaric acid co-crystal form A1,
b) a hemi fumaric acid co-crystal form A2,
c) a hemi fumaric acid co-crystal form NF1,
d) a hemi fumaric acid co-crystal form NF2,
e) a mono 3-hydroxybenzoic acid co-crystal form NF1,
f) a mono 3-hydroxybenzoic acid co-crystal form NF2,
g) a hemi tartaric acid co-crystal form NF1,
h) a hemi tartaric acid co-crystal form NF2,
i) a mono D -malic acid co-crystal form NF1,
j) a 1,5-naphthalenedisulfonic acid co-crystal form NF1 and
k) a mono 3,4-dihydroxybenzoic acid co-crystal form NF1.
5 . The crystalline anhydrous form A1 of (S)-7-oxa-2-aza-spiro[4,5]decane-2-carboxylic acid 17-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-thiazolo[4,5-c]pyridin-2-yl]-amide according to claim 2 ,
wherein the crystalline anhydrous form A1 has the characteristic peaks:
No.
°2θ (Cu—Kα 1 radiation) ± 0.2°
1
7.8
2
9.5
3
10.6
4
11.6
5
12.2
6
15.4
7
16.5
8
18.6
9
19.9
10
20.2
11
21.5
12
22.4
13
23.2
14
23.9
15
24.6
16
25.5
17
28.1
18
28.5
6 . The crystalline form of (S)-7-oxa-2-aza-spiro[4,5]decane-2-carboxylic acid [7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-thiazolo[4,5-c]pyridin-2-yl]-amide according to claim 4 , wherein the mono fumaric acid co-crystal form A1 has the characteristic peaks:
No.
°2θ (Cu—Kα 1 radiation) ± 0.2°
1
7.8
2
9.5
3
10.6
4
11.6
5
12.2
6
15.4
7
16.5
8
18.6
9
19.9
10
20.2
11
21.5
12
22.4
13
23.2
14
23.9
15
24.6
16
25.5
17
28.1
18
28.5
7 . The crystalline form of (S)-7-oxa-2-aza-spiro[4,5]decane-2-carboxylic acid [7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-thiazolo[4,5-c]pyridin-2-yl]-amide according to claim 4 , wherein the hemi fumaric acid co-crystal form A2 has the characteristic peaks:
No.
°2θ (Cu—Kα 1 radiation) ± 0.2°
1
6.6
2
9.7
3
11.5
4
13.4
5
14.1
6
14.7
7
16.5
8
18.0
9
18.5
10
19.4
11
20.0
12
21.4
13
22.9
14
24.1
15
26.8
8 . The crystalline form of (S)-7-oxa-2-aza-spiro[4,5]decane-2-carboxylic acid [7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-thiazolo[4,5-c]pyridin-2-yl]-amide according to claim 4 , wherein the hemi fumaric acid co-crystal form NF1 has the characteristic peaks:
No.
°2θ (Cu—Kα 1 radiation) ± 0.2°
1
6.7
2
8.1
3
10.1
4
12.3
5
16.1
6
16.3
7
16.7
8
19.3
9
21.5
10
22.9
11
25.7
9 . The crystalline form of (S)-7-oxa-2-aza-spiro[4.5]decane-2-carboxylic acid [7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-thiazolo[4,5-c]-pyridin-2-yl]-amide according to claim 4 , wherein the hemi fumaric acid co-crystal form NF2 has the characteristic peaks:
No.
°2θ (Cu—Kα 1 radiation) ± 0.2°
1
6.2
2
8.1
3
9.4
4
10.5
5
11.3
6
14.2
7
14.9
8
16.8
9
17.5
10
19.1
11
20.3
12
20.9
13
21.6
14
22.6
15
24.4
16
25.9
10 . The clystalline form of (S)-7-oxa-2-aza-spiro[4,5]decane-2-carboxylic acid [7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-thiazolo[4,5-c]pyridin-2-yl]-amide according to claim 4 , wherein the mono 3-hydroxybenzoic acid co-crystal form NF1 has the characteristic peaks:
No.
°2θ (Cu—Kα 1 radiation) ± 0.2°
1
7.3
2
10.6
3
13.9
4
14.5
5
16.1
6
16.6
7
17.4
8
18.1
9
18.7
10
19.4
11
20.0
12
20.8
13
21.3
14
23.1
15
23.5
16
25.1
17
25.7
18
27.2
19
28.1
11 . The crystalline form of (S)-7-oxa-2-aza-spiro[4,5]decane-2-carboxylic acid [7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-thiazolo[4,5-c]pyridin-2-yl]-amide according to claim 4 , wherein the mono 3-hydroxybenzoic acid co-crystal form NF2 has the characteristic peaks:
No.
°2θ (Cu—Kα 1 radiation) ± 0.2°
1
8.1
2
8.5
3
10.0
4
12.6
5
14.0
6
15.7
7
16.8
8
19.6
9
20.4
10
20.9
11
22.9
12
23.6
13
29.5
12 . The crystalline form of (S)-7-oxa-2-aza-spiro[4,5]decane-2-carboxylic acid [7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-thiazolo[4,5-c]pyridin-2-yl]-amide according to claim 4 , wherein the mono 3,4-dihydroxybenzoic acid co-crystal form NF1 has the characteristic peaks:
No.
°2θ (Cu—Kα 1 radiation) ± 0.2°
1
7.3
2
10.8
3
13.9
4
15.2
5
15.9
6
16.5
7
17.4
8
18.0
9
18.6
10
19.3
11
20.2
12
21.3
13
23.0
14
23.5
15
25.1
16
25.8
17
27.2
18
28.2
19
29.5
13 . The crystalline form of (S)-7-oxa-2-aza-spiro[4,5]decane-2-carboxylic acid [7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-thiazolo[4,5-c]pyridin-2-yl]-amide according to claim 4 , wherein the hemi tartaric acid co-crystal form NF1 has the characteristic peaks:
No.
°2θ (Cu—Kα 1 radiation) ± 0.2°
1
11.2
2
16.0
3
17.0
4
18.5
5
19.6
6
20.4
7
23.3
8
24.2
9
27.9
14 . The crystalline form of (S)-7-oxa-2-aza-spiro[4,5]decane-2-carboxylic acid [7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-thiazolo[4,5-c]pyridin-2-yl]-amide according to claim 4 , wherein the hemi tartaric acid co-crystal form NF1 has the characteristic peaks:
No.
°2θ (Cu—Kα 1 radiation) ± 0.2°
1
11.2
2
16.0
3
16.9
4
17.9
5
19.7
6
20.4
7
23.3
8
24.1
9
27.8
15 . The crystalline form of (S)-7-oxa-2-aza-spiro[4,5]decane-2-carboxylic acid [7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-thiazolo[4,5-c]pyridin-2-yl]-amide according to claim 4 , wherein the 1,5-naphthalenedisulfonic acid co-crystal form NF1 has the characteristic peaks:
No.
°2θ (Cu—Kα 1 radiation) ± 0.2°
1
6.5
2
8.4
3
10.1
4
10.4
5
12.0
6
13.1
7
14.8
8
15.3
9
16.9
10
17.7
11
18.2
12
18.6
13
19.4
14
20.3
15
21.0
16
21.8
17
22.2
18
22.8
19
25.0
16 . The crystalline form of (S)-7-oxa-2-aza-spiro[4,5]decane-2-carboxylic acid [7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-thiazolo[4,5-c]pyridin-2-yl]-amide according to claim 4 , wherein the mono D -malic acid co-crystal form NF1 has the characteristic peaks:
No.
°2θ (Cu—Kα 1 radiation) ± 0.2°
1
17.0
2
19.6
3
20.4
4
21.6
5
23.4
6
28.1
17 . A (S)-7-oxa-2-aza-spiro[4,5]decane-2-carboxylic acid [7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-thiazolo[4,5-c]pyridin-2-yl]-amide containing one or more of the crystalline form according to claim 1 .
18 . The (S)-7-oxa-2-aza-spiro[4,5]decane-2-carboxylic acid [7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-thiazolo[4,5-c]pyridin-2-yl]-amide essentially consisting of one or more of the crystalline form according to claim 1 .
19 . A method for the preparation of the crystalline form according to claim 4 , the method comprising:
suspending (S)-7-oxa-2-aza-spiro[4.5]decane-2-carboxylic acid [7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-thiazolo[4,5-c]pyridin-2-yl]-amide in an organic solvent at elevated temperature,
adding the equivalent amount of a co-former, and
carrying out a cooling crystallization.
20 . A medicament, comprising:
one or more of the crystalline form according to claim 1 or mixtures thereof in all ratios for the treatment and/or prophylaxis of cancer.
21 . A pharmaceutical preparation, comprising:
one or more of the crystalline form according to claim 1 or mixtures thereof in all ratios and optionally further excipients and/or adjuvants.
22 . A process for the preparation of a pharmaceutical preparation, the process comprising:
bringing that one or more of the crystalline form according to claim 1 or mixtures thereof in all ratios into a suitable dosage form together with a solid, liquid or semi-liquid excipient or adjuvant.