CRYSTALS OF (2-AMINO-4,5,6,7-TETRAHYDROBENZO[b]THIEN-3-YL)(4-CHLOROPHENYL)METHANONE
OwnerGeorge Laurence, Allan R. Moorman +1inventors
InventorsGeorge Laurence, Allan R. Moorman, Aeri Park
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Abstract
The present invention provides crystal forms of (2-amino-4,5,6,7-tetrahydrobenzo[b]thiophen-3-yl)(4-chlorophenyl)methanone of the formula processes for the production of such crystal forms; pharmaceutical compositions comprising such crystal forms; and methods of treating diseases or conditions modulated by the adenosine A1 receptor, in particular neuropathic pain, in a mammal in need thereof, by employing such crystal forms, or pharmaceutical compositions comprising such.
Claims29
A crystal form of anhydrous (2-amino-4,5,6,7-tetrahydrobenzo[b]thiophen-3-yl)(4-chlorophenyl)methanone (T-62) which crystal form (Form I) is substantially free of other polymorphic forms of T-62 and has at least one of the following properties:
- (a) a melting point of about 143° C.;
- (b) a X-ray diffraction pattern with characteristic X-ray diffraction peaks at diffraction angles (20) of about 19.6±0.2, 19.9±0.2, 20.8±0.2, 22.9±0.2 and 23.3±0.2;
- (c) an infrared absorption spectrum with absorption bands at about 3330±2, 3239±2, 2943±2, 1908±2 and 927±2 cm−1;
- and
- (d) a Raman spectrum with Raman shifts at about 3060±2, 2944±2, 1596±2, 1426±2 and 1391±2 cm−1.
A crystal form of anhydrous (2-amino-4,5,6,7-tetrahydrobenzo[b]thiophen-3-yl)(4-chlorophenyl)methanone (T-62) which crystal form (Form II) is substantially free of other polymorphic forms of T-62 and has at least one of the following properties:
- (a) a melting point of about 135° C.;
- (b) a X-ray diffraction pattern with characteristic X-ray diffraction peaks at diffraction angles (2θ) of about 16.5±0.2, 19.4±0.2, 20.3±0.2, 22.2±0.2, 23.6±0.2 and 26.2±0.2;
- (c) an infrared absorption spectrum with absorption bands at about 3344±2, 3243±2, 2955±2, 2930±2, 1895±2 and 1172±2 cm−1;
- and
- (d) a Raman spectrum with Raman shifts at about 3065±2, 2957±2, 1595±2, 1430±2 and 1394±2 cm−1.
A crystal form of (2-amino-4,5,6,7-tetrahydrobenzo[b]thiophen-3-yl)(4-chlorophenyl)methanone (T-62) which crystal form (Form III) is substantially free of other polymorphic forms of T-62 and has at least one of the following properties:
- (a) a melting point in the range of about 126-135° C.;
- (b) a X-ray diffraction pattern with characteristic X-ray diffraction peaks at diffraction angles (20) of about 15.5±0.2, 19.1±0.2, 19.4±0.2, 21.3±0.2 and 21.7±0.2;
- (c) an infrared absorption spectrum with absorption bands at about 3247±2, 2941±2, 1908±2 and 922±2 cm−1;
- and
- (d) a Raman spectrum with Raman shifts at about 3068±2, 2939±2, 1596±2 and 1436±2 cm−1.
A crystal form of (2-amino-4,5,6,7-tetrahydrobenzo[b]thiophen-3-yl)(4-chlorophenyl)methanone (T-62) which crystal form (Form IV) is substantially free of other polymorphic forms of T-62 and has at least one of the following properties:
- (a) a melting point of about 138° C.;
- and
- (b) a X-ray diffraction pattern with characteristic X-ray diffraction peaks at diffraction angles (2θ) of about 7.4±0.2, 18.8±0.2, 20.4±0.2 and 21.3±0.2.
A method for the production of Form I crystal form of (2-amino-4,5,6,7-tetrahydrobenzo[b]thiophen-3-yl)(4-chlorophenyl)methanone (T-62) which crystal form is substantially free of other polymorphic forms of T-62, wherein the method comprises:
- (a) dissolving T-62, in any of its forms, in a solvent to form a solution in which solvent T-62 is suitably soluble at an elevated temperature ranging from about 30° C. to the boiling point of the solvent, and in which solvent T-62 is only poorly soluble at a lower temperature ranging from about −78° C. to about 30° C.;
- (b) cooling the solution to the lower temperature to induce precipitation of the Form I crystal form of T-62;
- and
- (c) isolating and drying the precipitated Form I crystal form of T-62.
A method for the production of Form I crystal form of (2-amino-4,5,6,7-tetrahydrobenzo[b]thiophen-3-yl)(4-chlorophenyl)methanone (T-62) which crystal form is substantially free of other polymorphic forms of T-62, wherein the method comprises:
- (a) dissolving T-62, in any of its forms, in a first solvent to form a solution in which solvent T-62 is readily soluble at a temperature ranging from room temperature to the boiling point of the solvent;
- (b) treating the solution with a second solvent which is miscible with the first solvent, and in which T-62 is only poorly soluble to induce precipitation of Form I crystal form of T-62;
- (c) if desired, cooling the resulting mixture gradually to a temperature of about 10° C. to further induce precipitation of the Form I crystal form of T-62;
- and
- (d) isolating and drying the precipitated Form I crystal form of T-62.
A method for the production of Form I crystal form of (2-amino-4,5,6,7-tetrahydrobenzo[b]thiophen-3-yl)(4-chlorophenyl)methanone (T-62) which crystal form is substantially free of other polymorphic forms of T-62, wherein the method comprises converting the Form III or Form IV crystal form of T-62 into the Form I crystal form of T-62 by storing the former crystal form of T-62 under atmospheric, super-atmospheric or reduced pressure at a temperature ranging from about 20° C. to about 104° C. and in relative humidity ranging from about 0% to about 95%.
Dependencies are inferred from the claim text.