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Crystalline form of N-[4-[2(2-amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl) ethyl]benzoyl]-L-glutamic acid (Pemetrexed diacid)

IP.com Disclosure Number: IPCOM000242153D
Publication Date: 2015-Jun-20
Document File: 2 page(s) / 86K

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The IP.com Prior Art Database


X-ray Diffraction spectrum of Pemetrexed diacid.

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Crystalline form of N-[4-[2(2-amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl) ethyl]benzoyl]-L-glutamic acid (Pemetrexed diacid)

Pemetrexed disodium, developed by Eli Lilly and Company and approved by USFDA on September 24, 1996, as an antifolate antineoplastic agent was first disclosed in US 5,344,932. It is marketed by Eli Lilly and Company under the trade name ALIMTA®, for treatment of malignant pleural mesothelioma and for second-line treatment of non small cell lung cancer.

The preparation of pemetrexed disodium involves treatment of N-[4-[2(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid (pemetrexed diacid) with aqueous sodium hydroxide in an aqueous solvent mixture.

Pemetrexed diacid, having the structure mentioned below is generally prepared by the methods disclosed in Example 6 of US 5,416,211 and Example 13 of US 5,344,932.

Both US 5,416,211 and US 5,344,932 do not mention the nature of the polymorphic forms obtained by the disclosed methods, however, US 8,088,919 mentions that polymorphic forms A, B, C, D, E and F of Pemetrexed diacid are obtained by the disclosed methods.

We herein wish to report the polymorphic patterns of pemetrexed diacid obtained by preparing according to the methods disclosed in prior art.

Figure 1 discloses the X-ray powder diffraction (“PXRD”) pattern of crystalline pemetrexed diacid characterized by peaks at about 6.15, 10.45, 11.90, 13.75, 15.15, 15.85, 18.75, 20.10, 20.25, 21.15, 21.80 and 25.45 ± 0.2° (2θ).

Figure 1: X-ray powder diffrac...