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4S,4aS,5aR,12aS)-9-(2-(tert-butylamino) acetamido)-4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide acetonitrile solvate and (4S,4aS,5aR,12aS)-9-(2-(tert-butylamino) acetamido)-4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide acetone solvate and processes for their preparation

IP.com Disclosure Number: IPCOM000179292D
Publication Date: 2009-Feb-11
Document File: 4 page(s) / 808K

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4S,4aS,5aR,12aS)-9-(2-(tert-butylamino) acetamido)-4,7-bis(dimethylamino)- 1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2- naphthacenecarboxamide acetonitrile solvate and (4S,4aS,5aR,12aS)-9-(2-(tert- butylamino) acetamido)-4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro- 3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide acetone solvate and processes for their preparation (4S,4aS,5aR,12aS)-9-(2-(tert-butylamino) acetamido)-4,7-bis(dimethylamino)- 1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2- naphthacenecarboxamide (hereinafter referred to as "Tig") is depicted in the following structure:

C

H3

CH3

OH O OH

OH

H

O O

H N

NH

C

H3

NH

NH2

OH

O

H

  N C

H3 CH3

C

H3

CH3

 (4S,4aS,5aR,12aS)-9-(2-(tert-butylamino) acetamido)-4,7-bis(dimethylamino)- 1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2- naphthacenecarboxamide acetonitrile solvate (hereinafter referred to as "Tig acetonitrile solvate") can be prepared by providing a mixture of Tig and acetonitrile and precipitating Tig acetonitrile solvate from the mixture. The obtained material has a solvent-Tig ratio of 1:1.

 The solution may be obtained by heating the mixture at temperature of 50°C to 70°C. Precipitation may be promoted by mixing and cooling the mixture to a temperature of 0°C to 30°C and by adding an anti-solvent such as n-octane, n-hexane, n-heptane and cyclohexane to the mixture. Filtration of the suspension or evaporation under reduced pressure and elevated temperature may also facilitate the precipitation of the solvate.

 In one specific example Tig acetonitrile solvate was prepared by dissolving 50mg Tig in 6ml acetonitrile and heating to 70oC. n-Octane (4.5 ml) was added with stirring to and the solution was allowed to cool to 20oC. The solution was allowed to stand in an opened flask overnight at 20oC, which facilitated the crystallization of Tig acetonitrile solvate in the form of single crystals.

The following figure presents the XRPD pattern of Tig acetonitrile solvate.

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Main peaks are: 6.0, 6.9, 9.3, 10.2 and 23.0 + 0.2 degrees two theta. Additional peaks

are 12.1, 16.3, 18.0, and 21.0 + 0.2 degrees 2-theta.

 The above Tig acetonitrile solvate may be further characterized by single crystal X-ray analysis providing a monoclinic P21 crystalline form having unit cell parameters of: a =
14.979(1), b = 5.5374...