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Crystalline (S)-5-Methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]benzimidazole magnesium and processes for the preparation thereof

IP.com Disclosure Number: IPCOM000126437D
Publication Date: 2005-Jul-18

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The IP.com Prior Art Database

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   Crystalline (S)-5-Methoxy-2-[[(4-methoxy-3,5-dimethyl-2- pyridyl)methyl]sulfinyl]benzimidazole magnesium and processes for the preparation thereof

(S)-5-Methoxy-2-[[(4-methoxy-3,5-dimethyl-2- pyridyl)methyl]sulfinyl]benzimidazole is used for the treatment of heartburn and other symptoms associated with gastroesophageal reflux disease (GERD). It is also used for the short-term treatment of diagnostically confirmed erosive esophagitis (associated with GERD). Furthermore, (S)-5-Methoxy-2-[[(4-methoxy-3,5-dimethyl- 2-pyridyl)methyl]sulfinyl]benzimidazole is used to maintain symptom resolution and healing of erosive esophagitis, and it is also used for the treatment of ulcer, duodenal, Helicobacter pylori-associated (treatment adjunct), when in combination with clarithromycin and amoxicillin.

    (S)-5-Methoxy-2-[[(4-methoxy-3,5-dimethyl-2- pyridyl)methyl]sulfinyl]benzimidazole magnesium salt having the formula:

N

O

C H 3

O C H 3 C H 3

S

N

M g 2 +

N

O C H 3

2

is used for the preparation of enantiomerically pure(S)-5-Methoxy-2-[[(4-methoxy- 3,5-dimethyl-2-pyridyl)methyl]sulfinyl]benzimidazole.

    Novel crystalline forms of S)-5-Methoxy-2-[[(4-methoxy-3,5-dimethyl-2- pyridyl)methyl]sulfinyl]benzimidazole magnesium were found, and are described herein below.

Form T01

Figure 1: The crystalline form, denominated Form T01, has main x-ray powder diffraction peaks at about 5.9, 6.6, 7.6 and 18.9 degrees two-theta, ±0.2 degrees two- theta.

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Form T01 exists as a trihydrate and the water content may be of about 6.1% to about


7.3%.

Form T02

Figure 2: The crystalline form, denominated Form T02, has main x-ray powder diffraction peaks at about 5.7, 7.3, 16.9 and 24.8 degrees two-theta, ±0.2 degrees two- theta. Form T02 may be further characterized by X-ray powder diffraction peaks at about 6.6, 12.7, 20.48, 16.6, 17.9, 19.3, 23.0 and 23.54 degrees two-theta, ±0.2 degrees two-theta.

Form T03

Figure 3: The crystalline form, denominated Form T03, has main x-ray powder diffraction peaks at about 6.8, 17.0, 17.7, 23.6 and 24.4 degrees two-theta, ±0.2 degrees two-theta. Form T03 may be further characterized by X-ray powder diffraction peaks at about 5.9, 7.6, 12.9, 20.6, 23.6, 25.0, 25.5 and 27.4 degrees two- theta, ±0.2 degrees two-theta.

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Form T03 exists as a tetrahydrate and the water content may be of about 10%. Form T08

Figure 4: The crystalline form, denominated Form T08, has main x-ray powder diffraction peaks at about 5.1, 10.3 and 15.1 degrees two-theta, ±0.2 degrees two- theta. Form T08 may be further characterized by X-ray powder diffraction peaks at about 20.6, 22.5 and 26.2 degrees two-theta, ±0.2 degrees two-theta.

Form T09

Figure 5: The crystalline form, denominated Form T09, has main x-ray powder diffraction peaks at about 5.8, 11.8, 17.3, 17.5, 23.8, 25.8 and 30.3 degrees two-theta, ±0.2 degrees two-thet...