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SOLID STATE FORM OF INTERMEDIATE IN PREPARATION OF 4-(1-HYDROXY-1- METHYLETHYL)-2-PROPYL-1-[[2'-(1H-TETRAZOL-5-YL)[1,1'-BIPHENYL]-4- YL]METHYL]-1H-IMIDAZOLE -5-LITHIUM CARBOXYLATE

IP.com Disclosure Number: IPCOM000236920D
Publication Date: 2014-May-22
Document File: 5 page(s) / 146K

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The IP.com Prior Art Database

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SOLID STATE FORM OF INTERMEDIATE IN PREPARATION OF 4-(1-HYDROXY-1- METHYLETHYL)-2-PROPYL-1-[[2'-(1H-TETRAZOL-5-YL)[1,1'-BIPHENYL]-4-

YL]METHYL]-1H-IMIDAZOLE -5-LITHIUM CARBOXYLATE

4-(1-Hydroxy-1-methylethyl)-2-propyl-1-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4- yl]methyl]-1H-imidazole -5-Lithium carboxylate (referred to as "Compound 1") has the fallowing chemical structure:

Compound 1

    Compound 1 may be an intermediate in the synthesis of (5-methyl-2-oxo-2H-1,3-dioxol-4- yl)methyl 4-(2-hydroxypropan-2-yl)-2-propyl-1-({4-[2-(2H-1,2,3,4-tetrazol-5- yl)phenyl]phenyl}methyl)-1H-imidazole-5-carboxylate.

4-(1-Hydroxy-1-methylethyl)-2-propyl-1-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]- 1H-imidazole -5-carboxylic ethyl ester (referred to as "Compound 2") is an intermediate in the preparation of Compound 1, and has the following chemical structure:

Compound 2

Described hereinafter are crystalline forms of Compound 2.

1


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Figure 1: XRPD pattern of crystalline form of Compound 2 prepared by Procedure in Example 1

Main PXRD peaks:

    4.3; 8.7; 9.1; 9.4; 9.8; 10.6; 10.9; 11.9; 13.1; 13.7; 14.6; 15.0; 15.5; 16.1; 16.7; 17.2; 18.1;
18.9; 19.2; 19.7; 20.0; 20.5; 21.1; 21.4; 22.1; 22.6; 23.5; 24.6; 25.8; 26.4; 28.4; 29.6 and 31.2 degrees two theta ± 0.2 degrees 2-theta.

2


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Figure 2: XRPD pattern of crystalline form of Compound 2 prepared by Procedure in Example 2

Main PXRD peaks:

    4.7; 5.7; 8.9; 9.5; 10.2; 11.4; 12.8; 14.2; 15.7; 16.3; 16.9; 17.3; 18.3; 19.1; 19.9; 20.4; 20.9;
21.3; 22.0; 22.4; 23.2; 23.7; 24.5; 25.3; 25.6; 25.9; 26.4; 27.0; 28.3; 29.8; 30.9; 33.7; 35.1; 36.0; 39.8 degrees two theta ± 0.2 degrees 2-theta.

3


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Powder X-ray Diffraction (XRD) method

X-ray diffraction was performed on X-Ray powder diffractometer:
Bruker D8 Advance; CuK_ radiation (λ = 1.5418 Å); Lynx eye detector; laboratory temperature 22- 25 °C; PMMA specimen holder ring. Prior to analysis, the samples were gently ground by means of mortar and pestle in order to obtain a fine powder. The ground sample was adjusted into a cavity of the sample holder and the surface of the sample was smoothed by means of a cover glass.

Measurement parameters:

Scan range: 2 - 40 degrees 2-theta;

Scan mode: continuous;

Step size: 0.05 degrees;

Time per step: 0.1 s;

Sample spin: 60 rpm;

Sample holder: PMMA specimen holder ring. Divergence slit: 1.0

Examples

Example 1: Procedure for the preparation of 4-(1-Hydroxy-1-methylethyl)-2-propyl-1-[[2'-(1H-

tetrazol-5-...