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CRYSTALLINE FORM OF N-(CARBAMOYLMETHYL-4-PHENYL-2-PYRROLIDINONE AND INTERMEDIATES THEREOF

IP.com Disclosure Number: IPCOM000212593D
Publication Date: 2011-Nov-17
Document File: 4 page(s) / 47K

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The IP.com Prior Art Database

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CRYSTALLINE FORM OF N-(CARBAMOYLMETHYL-4-PHENYL-2- PYRROLIDINONE AND INTERMEDIATES THEREOF

N-(Carbamoylmethyl-4-phenyl-2-pyrrolidinone, referred as to 'Compound P' has the following structure:

    Described hereinafter, are crystalline form of Compound P and crystalline forms of its intermediate phenylpyrrolidin-2-one, referred as to 'Compound III' of the following structure:

Form F1 of Compound P:

Form F1 of Compound P can be characterized by data selected from a group consisting of: X-ray powder diffraction pattern, having peaks at about 8.6, 9.0, 16.1,


17.2, 19.0, 20.5 and 22.0±0.2 degrees two-theta; an X-ray powder diffraction pattern substantially as depicted in Figure 1; and combinations thereof.

Figure 1: XRPD pattern of Form F1 of Compound P

Form PP1 of Compound III:


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Form PP1 of Compound III can be characterized by data selected from a group consisting of: X-ray powder diffraction pattern, having peaks at about 6.0, 10.9, 13.9 and 19.7±0.2 degrees two-theta; an X-ray powder diffraction pattern substantially as depicted in Figure 2; and combinations thereof.

Figure 2: XRPD pattern of Form PP1 of Compound III

Counts

A mixture of Form PP1 and Form PP2 of Compound III:

A mixture of Form PP1 and Form PP2 of Compound III can be characterized by data selected from a group consisting of: X-ray powder diffraction pattern, having peaks at about 6.0, 6.5, 16.7, 17.1, 22.5 and 23.8 ±0.2 degrees two-theta; an X-ray powder diffraction pattern substantially as depicted in Figure 3; and combinations thereof. Figure 3: XRPD pattern of a mixture of Form PP1 and Form PP2 of Compound III

Counts

3000

2000

1000

0

10

30

20

Position [°2Theta] (Copper (Cu))

3000

2000

1000

0

10

30

20

Position [°2Theta] (Copper (Cu))


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X-Ray Powder Diffraction Analysis (XRPD) experimental parameters.

Instrument

                 Philips X'Pert PRO powder diffractometer Sample holder preparation

Sample is applied directly on silicon PW1817/32 "zero background" holder

Instrument

Philips X'Pert PRO

Generator

PW3040; 45 kV, 40 mA

X-Ray tube

PW3373/00; Cu anode LFF

X-ray radiation λ(CuKα1) = 1.540598 Å

Temperature

295±5K

Scan rate


0.05 o/sec

Step size


0.0167 o

Example 1:

    50 g of crude N-(Carbamoylmethyl-4-phenyl-2-pyrrolidinone was charged with 250 mL of isopropyl alcohol at 30 ± 5°C. Heated to reflux for about 60-90 minutes, cool it to 25 ± 5°C and maintain for 4-5hrs. The slurry was filtered and washed with isopropyl alcohol and than dried under vacuum at 50°C. The crystal harvested was N-(Carbamoylmethyl-4-phenyl-2-pyrrolidino...