Traitement en cours

Veuillez attendre...

Paramétrages

Paramétrages

Aller à Demande

1. WO2020156982 - MONOHYDRATE DE CHLORHYDRATE DE ROGARATINIB ET ÉTATS SOLIDES ASSOCIÉS

Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

[ EN ]
Claims:

We claim:

1 Compound (III)


2. The form of the compound of claim 1 characterized by a X-ray powder diffractogram measured at 25°C and with Cu-K alpha 1 as radiation source displaying at least the following reflections, quoted as 2Q value ± 0.2°: 9.3, 10.6, and 13.3.

3. The form of the compound of claim 1 characterized by a X-ray powder diffractogram measured at 25°C and with Cu-K alpha 1 as radiation source displaying at least the following reflections, quoted as 2Q value ± 0.2°: 9.3, 10.6, 13.3, 20.7, and 23.3.

4 The form of the compound of claim 1 characterized by a X-ray powder diffractogram measured at 25°C and with Cu-K alpha 1 as radiation source displaying at least the following reflections, quoted as 2Q value ± 0.2°: 9.3 , 10.6 , 11.4 , 13.3 , 20.7, 23.3 , and 26.0.

5. The form of the compound of claim 1 characterized by a X-ray powder diffractogram measured at 25°C and with Cu-K alpha 1 as radiation source displaying at least the following reflections, quoted as 2Q value ± 0.2°: 6.8, 9.3, 10.6, 11.4, 13.3, 20.7, 23.3, 24.6, 26.0, and 27.6.

6 A pharmaceutical composition comprising pseudopolymorphic form (III) of the compound of formula (I) and optionally further pharmaceutically acceptable excipients.

7. The pharmaceutical composition of claim 6 comprising crystalline form (III) of the compound of the formula (I) mainly and no significant fractions of another form of the compound of the formula (I) and optionally further pharmaceutically acceptable excipients.

8 A crystalline form of the compound of any of claims 1 to 5 for use in the treatment and/or prophylaxis of cancer.

9. A pharmaceutical composition of any of claims 6 to 7 for use in the treatment and/or prophylaxis of proliferative disorders, such as cancer and tumor diseases.

10 Use of a compound as defined in any of claims 1 to 5 for the manufacture of a pharma- ceutical composition for the treatment or prevention of proliferative disorders, such as cancer and tumor diseases.

11 Use of a compound as defined in any of claims 1 to 5 for the manufacture of a tablet which is physically and chemically stable.

12 A method of treating or preventing proliferative disorders, such as cancer and tumor diseases in a mammal, comprising administering to a mammal in need thereof a thera- peutically effective amount of the compound as defined in any of claims 1 to 5.

13. A process for producing the crystalline form (III) of the compound of formula (I) comprising the step of allowing the compound of formula (I) to react, by dissolution or suspension of the compound of formula (I) in an inert solvent and addition of an acid or acid precursor.

14. The process of claim 13, wherein the compound of formula (I) is allowed to react by dissolution or suspension of the compound of formula (I) in THF or EtOH and water, and addition of HC1.

15. The process of claim 14, wherein the compound of formula (I) is produced by allowing a compound of formula (VII)

to react in the presence of THF and water with K2CO3 and a palladium catalyst with a compound of formula (VIII)

16. The process of claim 15, wherein the compound of formula (VII) is produced by allowing a compound of formula (V) to react

with a compound of formula (XIII)

with paraformaldehyde in the presence of an acid to an thereby producing a compound of formula (VI),

and then allowing the compound of formula (VI) to react with a bromination agent.

17. The process of claim 16, wherein the compound of formula (V) is produced by allowing a compound of formula (IV) to react

with an acid thereby producing a compound of formula (XXII),

and then allowing (XXII) to react with methanol in the presence of a base, thereby producing a compound of formula (XXIII),


and then allowing (XXIII) to react with formamidine acetate and a base.

18. The process of claim 17, wherein the compound of formula (IV) is produced by allowing a compound of formula (X)

to react with B0C-NH-NH2 to form a compound of formula (XI)

which is allowed to react with CISO2NCO to form a compound of formula (XII)

which is, in turn, allowed to react with N-bromosuccinimide to form a compound of formula (IX)

which is allowed to react with metal organic reagents, preferably with methyl magnesium bromide and butyl lithium, in addition to paraformaldehyde to form a compound of formula (IV).