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POLYMORPH OF 1-(3,4-DIMETHYLPHENYL)-3-METHYL-1H-PYRAZOL-5-OL AND 3'-AMINO-2'-HYDROXYBIPHENYL-3-CARBOXYLIC ACID

IP.com Disclosure Number: IPCOM000180992D
Publication Date: 2009-Mar-23
Document File: 4 page(s) / 87K

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The IP.com Prior Art Database

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POLYMORPH OF 1-(3,4-DIMETHYLPHENYL)-3-METHYL-1H-PYRAZOL-

5-OL AND 3'-AMINO-2'-HYDROXYBIPHENYL-3-CARBOXYLIC ACID

1-(3,4-dimethylphenyl)-3-methyl-1H-pyrazol-5-ol (referred as DMPMP) of the following structure:

and 3'-amino-2'-hydroxybiphenyl-3-carboxylic acid (referred as BPCA) of the following structure:

are intermediates of (Z)-3'-(2-(1-(3,4-dimethylphenyl)-3-methyl-5-oxo-1H-pyrazol- 4(5H)-ylidene)hydrazinyl)-2'-hydroxybiphenyl-3-carboxylic acid (referred as ETP) of the following structure:

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ETP is a c-mpl receptor agonist that is marketed under the trade name Promacta® by GlaxoSmithKline and Ligand Pharmaceuticals for the treatment of conditions leading to thrombocytopenia.

Two crystalline forms of the above intermediates were found and are described below.

DMPMP crystalline form:

The crystalline form of DMPMP can be characterized by data selected from a group consisting of: X-ray powder diffraction having peaks at about 10.72, 12.93, 17.95,
20.96, and 26.01 ± 0.2 degrees two-theta; a PXRD pattern described in Figure 1; and combination thereof.

Figure 1 shows a PXRD pattern of DMPMP crystalline form:

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The DMPMP crystalline Form can be further characterized by a PXRD having peaks at about 9.7, 14.36, 17.09, 23.14 and 27.84 ± 0.2 degrees two-theta.

BPCA crystalline form:

The crystalline form of BPCA can be characterized by data selected from a group consisting of: X-ray powder diffraction having peaks at about 8.51, 14.87, 19.66,
26.19 and 32.66 ± 0.2 degrees two-theta; a PXRD pattern described in Figure 2; and combination thereof.

Intensity (counts)

5 10 15 20 25 30 35

2Theta (°)

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Figure 2 shows a PXRD pattern of BPCA crystalline form:

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