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Crystalline form of diethylamine salt and calcium salt of (S)-tetrahydrofuran-3-yl (2S,3R)-4-(N-isobutyl-4-nitrophenylsulfonamido)-1-phenyl-3-(phosphonooxy)butan-2-ylcarbamate

IP.com Disclosure Number: IPCOM000202279D
Publication Date: 2010-Dec-13
Document File: 4 page(s) / 114K

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    Crystalline form of diethylamine salt and calcium salt of (S)-tetrahydrofuran-3-yl (2S,3R)-4-(N-isobutyl-4-nitrophenylsulfonamido)-1-phenyl-3-(phosphonooxy)butan-2- ylcarbamate

    (S)-tetrahydrofuran-3-yl (2S,3R)-4-(N-isobutyl-4-nitrophenylsulfonamido)-1-phenyl-3- (phosphonooxy)butan-2-ylcarbamate(referred to as "NFOS") of the following formula;

Me

HN N

is an intermediate in the synthesis of Calcium (2R,3S)-1-(4-amino-N-isobutylphenylsulfonamido)- 4-phenyl-3-(((S)-tetrahydrofuran-3-yloxy)carbonylamino)butan-2-yl phosphate(referred to as "FSM").

     FSM is a phosphate ester prodrug of the protease inhibitor and antiretroviral drug (3S)- oxolan-3-yl N-[(2S,3R)-3-hydroxy-4-[N-(2-methylpropyl)(4-aminobenzene)sulfonamido]-1- phenylbutan-2-yl]carbamate(referred to as "AMP").

Crystalline forms of salts of NFOS were found and are described herein below.

    A crystalline form of NFOS diethylamine salt can be characterized by data selected from: a powder XRD pattern with peaks at about 9.1, 13.1, 16.9, 21.1 and 26.8° 2θ ± 0.2° 2θ; a powder XRD pattern as depicted in figure 1, and combinations thereof.

Figure 1 shows a powder XRD pattern of NFOS diethylamine salt

P

  HO O HO

       Me O

S

O O

NO2

O

O

O


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Intensity (counts)

6400

3600

1600

400

0

5 10 15 20 25 30 35

2Theta (°)

The NFOS diethylamine salt can be further characterized by PXRD peaks at about 10.2,
15.0, 16.2, 18.4 and 20.3 ° 2θ ± 0.2° 2θ.

    A crystalline form of NFOS calcium salt, designated form A can be characterized by data selected from: a powder XRD pattern with peaks at about 5.6, 9.5, 17.6, 19.2 and 19.9° 2θ ± 0.2° 2θ; a powder XRD pattern as depicted in figure 2, and combinations thereof.

Figure 2 shows a powder XRD pattern of NFOS calcium salt form A

Intensity (counts)

14400

10000

6400

3600

1600

400

0

5 10 15 20 25 30 35

2Theta (°)

The NFOS calcium salt form A can be further characterized by PXRD peaks at about 11.0,
14.5, 16.5, 21.9 and 25.8 ° 2θ ± 0.2° 2θ.


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The NFOS calcium salt form A may be a hydrate.

    A crystalline form of NFOS calcium salt designated form B can be characterized by data selected from: a powder XRD pattern with peaks at about 5.2, 8.9, 16.9, 18.6 and 21.2° 2θ ± 0.2° 2θ; a powder XRD pattern as depicted in figure 3, and combinations thereof.

Figure 3 shows XRPD pattern of NFO...