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CRYSTALLINE FORMS OF 10-DEACETYL BACCATINE III

IP.com Disclosure Number: IPCOM000234168D
Publication Date: 2014-Jan-15
Document File: 5 page(s) / 79K

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The IP.com Prior Art Database

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CRYSTALLINE FORMS OF 10-DEACETYL BACCATINE III

    (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)- 12b-(Acetyloxy)-12-(benzoyloxy)- 1,2a,3,4,4a,6,9,10,11,12,12a,12b- dodecahydro-4,6,9,11-tetrahydroxy- 4a,8,13,13- tetramethyl-7,11-methano- 5H-cyclodeca(3,4)benz(1,2-b) oxet-5-one (10-Deacetyl Baccatine III), referred to as Compound 1, has the following formula:

O

HO

Compound 1


Compound 1 can be used as starting material for preparation of taxoid active pharmaceutical ingredients such as 1,7β,10β-trihydroxy-9-oxo-5β,20-epoxytax-11- ene-2α,4,13α-triyl 4-acetate 2-benzoate 13-{(2R,3S)-3-[(tert-butoxycarbonyl)amino]- 2-hydroxy-3-phenylpropanoate}; or (2α,4α,5β,7β,10β,13α)-4,10-bis(acetyloxy)-13- {[(2R,3S)- 3-(benzoylamino)-2-hydroxy-3-phenylpropanoyl]oxy}- 1,7-dihydroxy-9- oxo-5,20-epoxytax-11-en-2-yl benzoate; or (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4- (Acetyloxy)-15-{[(2R,3S)-3-{[(tert-butoxy)carbonyl]amino}-2-hydroxy-3- phenylpropanoyl]oxy}-1-hydroxy-9,12-dimethoxy-10,14,17,17-tetramethyl-11-oxo-6- oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-ene-2-yl benzoate.

    Provided are the solid state forms of Compound 1 and processes for preparation thereof.

Acetone solvate crystalline form of Compound 1:

   Samples of acetone solvate of Compound 1were prepared according to Example 1 and were analyzed by X-ray powder diffraction ("XRPD").

Figure 1:An XRPD pattern of acetone solvate of Compound 1:

HO

OH

HO

H BzO AcO

O


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Intensity (cps)

3000

2500

2000

1500

1000

500

0

5 10 15 20 25 30 35 2Theta (°)

Main XRPD peaks: 6.5, 9.1, 9.5, 11.3, 12.4, 13.1, 13.4, 14.4, 14.8, 15.0, 16.4,


16.9, 18.3, 19.2, 19.7, 20.5, 21.1, 22.0, 23.2, 24.0, 24.7, 25.6, 26.4, 26.9, 27.5, 28.1,


29.2, 29.4, 30.3, 30.7, 31.3, 31.7, 32.5, 33.2, 34.0, 35.1, 36.3, 37.0, 37.8 and 39.7 °2θ ± 0.2 °2θ.

Anhydrous crystalline form of Compound 1:

    Samples of anhydrous form of Compound 1 were prepared according to Example 2 and were analyzed by X-ray powder diffraction ("XRPD").

Figure 2:An XRPD pattern of anhydrous form Compound 1:

Intensity (cps)

1500

1000

500

0

5 10 15 20 25 30 35 2Theta (°)


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Main XRPD peaks: 9.4, 10.3, 10.7, 12.9, 14.2, 16.0, 16.6, 18.2, 19.0, 19.1,


19.6, 20.8, 21.7, 21.8, 22.9, 23.5, 24.6, 25.3, 25.7, 26.1, 27.8, 28.4, 28.8, 29.1, 29.6,


30.2, 30.6, 31.1, 31.5, 32.1, 32.4, 33.0, 33.3, 35.4, 35.7, 36.1, 36.9, 37.2, 37.8, 38.8 and 39.2 °2θ ± 0.2 °2θ.

Tetrahydrofuran solvate crystalline form of Compound 1:

   Samples of tetrahydrofuran (THF) solvate form of Compound 1 were prepared according to Example 3 and were analyzed by X-ray powder diffraction ("XRPD").


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Figure 3:An XRPD pattern of THF solvate of Compound 1:

Main XRPD peaks: 6.6, 9.2, 11.3, 12.4, 13.1, 13.6, 14.6, 15....