Provided herein are free base crystalline forms, crystalline salts, and an amorphous salts of omecamtiv mecarbil.

The present invention provides freebase and salt forms, and compositions and methods thereof, useful for treating various conditions in which aldehyde toxicity is implicated in the pathogenesis by the administration of small molecule therapeutics acting as a scavenger for toxic aldehydes.

A process for the manufacturing of fire suppressing crystals having a high Q-factor particle size distribution, said fire suppression crystals being intended for use as a fire suppressing additive in polymer compositions, the process comprising the steps; a) Preparing a mother liquor comprising water and a salt composition obtained in step c) or d), the temperature of said mother liquor being adjusted to 10-50 C. and comprising said salt composition to a level of at least 90% of saturation. Calcium hydroxide is added to the mother liquor to a level of at least 90% of saturation. b) Preparing an acid solution comprising water and two or more acids selected from the group consisting of; C.sub.2-C.sub.6 mono-, di- and/or tri-carboxylic acids, and optionally a phosphorous compound. The temperature of said acid solution is adjusted to 20-90 C. 31 and comprising acids to a level of at least 50% of saturation. c) The mother liquor, comprising calcium hydroxide, obtained from step a) is subjected to intense agitation under which the acid solution obtained from step b) is slowly added to said mother liquor allowing reaction to form salt until supersaturation is achieved while maintaining PH at a level securing that no unreacted acids remains after reaction, d) Crystals formed in the reaction of step c) is continuously or discontinuously removed from the reaction product of step c).

A process for the manufacturing of fire suppressing crystals having a high Q-factor particle size distribution, said fire suppression crystals being intended for use as a fire suppressing additive in polymer compositions, the process comprising the steps; a) Preparing a mother liquor comprising water and a salt composition obtained in step c) or d), the temperature of said mother liquor being adjusted to 10-50 C. and comprising said salt composition to a level of at least 90% of saturation. Calcium hydroxide is added to the mother liquor to a level of at least 90% of saturation. b) Preparing an acid solution comprising water and two or more acids selected from the group consisting of; C.sub.2-C.sub.6 mono-, di- and/or tri-carboxylic acids, and optionally a phosphorous compound. The temperature of said acid solution is adjusted to 20-90 C. 31 and comprising acids to a level of at least 50% of saturation. c) The mother liquor, comprising calcium hydroxide, obtained from step a) is subjected to intense agitation under which the acid solution obtained from step b) is slowly added to said mother liquor allowing reaction to form salt until supersaturation is achieved while maintaining PH at a level securing that no unreacted acids remains after reaction, d) Crystals formed in the reaction of step c) is continuously or discontinuously removed from the reaction product of step c).

A method of catalytic oxidation of a lignite using oxygen as an oxidant at atmospheric pressure is provided. The method includes the following steps, pulverizing the lignite to 200-mesh or less; drying the pulverized lignite at a temperature of 80 C. in vacuum for 10 h; weighing 0.5 g of the dried lignite and sequentially adding 10 ml of acetic acid, 0.5 mmol of a catalyst and 0.15-0.25 mmol of a cocatalyst into a round-bottom flask filled with the oxygen, keeping oxygen pressure at 0.1 MPa, reacting at a temperature of 80-120 C. for 4-12 h; using oxygen as the oxidant to catalytically oxidize the reacted lignite at an atmospheric pressure of 0.1 MPa; filtering after the reaction is finished; decompressing the filtrate to remove the acetic acid, adding a small amount of ethyl acetate to dissolve, and using an excess CH.sub.2N.sub.2/ether solution to esterify for 10 h at room temperature; and analyzing the esterified product through a gas chromatography-mass spectrometer.

A method of catalytic oxidation of a lignite using oxygen as an oxidant at atmospheric pressure is provided. The method includes the following steps, pulverizing the lignite to 200-mesh or less; drying the pulverized lignite at a temperature of 80 C. in vacuum for 10 h; weighing 0.5 g of the dried lignite and sequentially adding 10 ml of acetic acid, 0.5 mmol of a catalyst and 0.15-0.25 mmol of a cocatalyst into a round-bottom flask filled with the oxygen, keeping oxygen pressure at 0.1 MPa, reacting at a temperature of 80-120 C. for 4-12 h; using oxygen as the oxidant to catalytically oxidize the reacted lignite at an atmospheric pressure of 0.1 MPa; filtering after the reaction is finished; decompressing the filtrate to remove the acetic acid, adding a small amount of ethyl acetate to dissolve, and using an excess CH.sub.2N.sub.2/ether solution to esterify for 10 h at room temperature; and analyzing the esterified product through a gas chromatography-mass spectrometer.

The invention relates to novel crystalline forms of 3-(4-amino-l-oxo-l,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione, including a novel urea cocrystal of 3-(4-amino-l-oxo-l,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione; a novel gallic acid cocrystal of 3-(4-amino-l-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione; a novel propyl gallate cocrystal of 3-(4-amino-l-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione; and a novel L-tartaric acid cocrystal of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione. The preparation and characterization of the novel crystalline forms according to various embodiments of the invention are described. The invention also relates to pharmaceutical compositions containing the novel crystalline forms, and the therapeutic use of the novel crystalline forms.

The invention relates to novel crystalline forms of 3-(4-amino-l-oxo-l,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione, including a novel urea cocrystal of 3-(4-amino-l-oxo-l,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione; a novel gallic acid cocrystal of 3-(4-amino-l-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione; a novel propyl gallate cocrystal of 3-(4-amino-l-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione; and a novel L-tartaric acid cocrystal of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione. The preparation and characterization of the novel crystalline forms according to various embodiments of the invention are described. The invention also relates to pharmaceutical compositions containing the novel crystalline forms, and the therapeutic use of the novel crystalline forms.

The present invention provides compounds and compositions thereof which are useful as inhibitors of Bruton's tyrosine kinase and which exhibit desirable characteristics for the same.

The present invention provides compounds and compositions thereof which are useful as inhibitors of Bruton's tyrosine kinase and which exhibit desirable characteristics for the same.