FORM - 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(Section 10 and Rule 13)
1. TITLE OF THE INVENTION: - A process for the preparation of Nilutamide and Triethylenemelamine.
2. ADDRESS OF THE APPLICANT:-
1)M. M. V. Ramana
NATIONALITY: INDIAN
Department of Chemistry, University of Mumbai, Vidyanagari, Santacruz (East), Mumbai- 400 098. India.
3. PREAMBLE TO THE DESCRIPTION - COMPLETE
The following specification particularly describes the invention and the manner in which it is to be performed.

4.DESCRIPTI0N:-Title:-
A process for the preparation of Nilutamide and Triethylenemelamine.
Abstract of the invention:-
The present invention relates to the synthesis of Nilutamide and Triethylenemelamine by simple and eco-friendly method. The main object of the present invention is to synthesize the Nilutamide and Triethylenemelamine through N-arylation by using KF/Al2O3 under solventless and transition metal free condition.
Background of invention and Prior art:-
Nilutamide is an antiandrogen medication used in the treatment of advanced stage prostate cancer. Nilutamide blocks the androgen receptor, preventing its interaction with testosterone. Because most prostate cancer cells rely on the stimulation of the androgen receptor for growth and survival, nilutamide can prolong life in men with prostate cancer. Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing. The cancer cells may spread from the prostate to other parts of the body, mainly the bones and lymph nodes. Prostate cancer may cause pain, erectile dysfunction or difficulty in urinating. Other symptoms can potentially develop during later stages of the disease. Nilutamide is marketed under the name Nilandron in the United States and under the name Anandron in Canada.
Triethylenemelamine is a drug used in chemotherapy. Chemotherapy is the treatment of cancer with one or more cytotoxic antineoplastic drugs (chemotherapeutic agents) as part of a standardized regimen. Chemotherapy may be given with a curative intent or to palliate symptoms it may aim to prolong life. It is often used in conjunction with other cancer treatments, such as radiation surgery or therapy. Certain chemotherapeutic agents also have a role in the treatment of other conditions, including Crohn's disease, ankylosing spondylitis, rheumatoid arthritis, psoriasis, psoriaticarthritis, systemiclupus erythematosus, multiple sclerosis and scleroderma. Traditional chemotherapeutic agents act by killing cells that divide rapidly, one of the main properties of most cancer cells. This means that chemotherapy also harms cells that divide rapidly under normal circumstances: digestive tract, cells in the bone marrow and hair follicles. This results in the most common side-effects of chemotherapy: myelosuppression (decreased production of blood cells, hence also immunosuppression), mucositis (inflammation of the lining of the digestive tract), and alopecia (hair loss).
Such drugs are well known in the prior arts including U.S. Pat. No. US 2006 / 7005124 B2; US 1993 / 5274162 A; WO 2002 / 2002002077 A3; V. B. Lokeshwar, L. E. Lopez, D. Munoz, A.

Chi, S. P. Shirodkar, S. D. Lokeshwar, D. 0. Escudero, N. Dhir, N. Altman Cancer Res. 2010, 70(7), 2613-23; S. F. Brady, J. M. Pawluczyk, P. K. Lumma, D. M. Feng, J. M. Wai, J. Jones D. DeFeo-Jones, B. K. Wong, C. Miller-Stein, J .H. Lin, A. Oliff, R. M. Freidinger, V. M. Garsky J. Med. Chem. 2002,45(21), 4706-15.
The methods used for the preparation of these drugs suffers from one of the disadvantages such as extended time, harsh reaction conditions, tedious preparation procedure, use of solvents and transition metals. Thus there is scope for the synthesis of these drugs by simple and eco-friendly method. The present invention describes synthesis of Nilutamide and Triethylenemelamine in one step through N-arylation in absence of transition metals and under mild conditions.
Description of the inventiom-
The main objective of the present invention is to synthesize Nilutamide and Triethylenemelamine that avoids (1) multi-step reactions, (2) solvents (3) transition metal, (4) tedious work up.
The present invention is successful in attaining all the above objectives. According to the invention there is provided a process for the preparation of Nilutamide (Scheme 1) and Triethylenemelamine (Scheme 2).
Scheme 1



Examples: -
Example 1
Preparation of 5,5-dimethyl-3-(4-nitro-3-(trifluoromethyl)phenyl)imidazolidine-2,4-dione
(Nilutamide)
Into a mixture of dry KF (0.3g) and basic Al2O3 (0.5 g) add 5,5-dimethylimidazolidine-2,4-dione (2a) (0.005M) and stir it well. Now add 4-chloro-l-nitro-2-(trifluoromethyl)benzene (la) (0.005M) at room temperature with continuous stirring for 8 minutes. After completion of reaction (TLC) the solid was extracted with dichloromethane and filtered. The dichloromethane extract was distilled and residue purified by crystallization/column chromatography, whereby 5, 5-dimethyl-3-(4-nitro-3-(trifluoromethyl)phenyl)imidazolidine-2,4-dione (3a) was obtained as solid (78% Yield) m.p.:152-153°C (Konieczny Marek. PL 1994/164184 Bl). The spectral data was also consistent with the reported data (PCT Int. Appl. 2010/ 2010106078, 23)
Example 2
Preparation of 2,4,6-tri(azindin-l-yI)-l,3,5-triazine(Triethylenemelamine)
Into a mixture of dry KF (0.3g) and basic Al2O3 (0.5 g) add aziridine (2b) (0.015M) and stir it well. Now add 2,4,6-trichIoro-l,3,5-triazine (lb) (0.005M) at room temperature with continuous stirring for 5 minutes. After completion of reaction (TLC) the solid was extracted with dichloromethane and filtered. The dichloromethane extract was distilled and residue purified by crystallization/column chromatography, whereby 2,4,6-tri(aziridin-l-yl)-l,3,5-triazine (3b) was obtained as solid (85% Yield) m.p.: dec. at 139 °C (V. P. Wystrachd, D. W. Kaiser, F. C. Schaefer Journal of the American Chemical Society, 1955, 77, 5915-18). Anal. Calcd. For C9H12N6: C, 52.93; H, 5.92; N, 41.14. Found: C, 52.81; H, 5.89; N, 41.10.

We Claim:-
1) Synthesis of 5, 5-dimethyl-3-(4-nitro-3-(trifluoromethyl)phenyl)imidazolidine-2,4-dione
(Nilutamide) (3a) as described in example 1 in one step via N-arylation using KF/AI2O3 without
solvent and transition metal, at room temperature in a short reaction time of 8 minutes.
2) Synthesis of 2,4,6-tri(aziridin-l-yl)-l,3,5-triazine (Triethylenemelamine) (3b) as described in example 2 in one step via N-arylation using KF/Al2O3 without solvent and transition metal, at room temperature in a short reaction time of 5 minutes.
3) Green method for the synthesis of Nilutamide (3a) and Triethylenemelamine (3b) as described in example 1 and example 2.