Process for the synthesis of the sodium salt of 4-[[(1R)-2-[5-(2-fluoro-3-methoxyphenyl)-3-[[2-fluoro-6-(trifluoromethyl)-phenyl]methyl]-3,6-dihydro-4-methyl-2.6-dioxo-1(2H)-pyrimidinyl]-1-phenylethyl]amino]-butanoic acid (elagolix sodium salt) and intermediates of said process

A process for the synthesis of the sodium salt of Elagolix, which comprises the following steps:

• a) reaction of the compound 5-bromo-1-[2-fluoro-6-(trifluoromethyl)benzyl]-6-methylpyrimidine-2,4(1H,3H)-dione (N-6) with D-Boc-phenylglycinol to obtain the intermediate 5-bromo-1-[2-fluoro-6-(trifluoromethyl)benzyl]-6-methyl-3-[2(R)-tert-butoxycarbonylamino-2-phenylethyl]-pyrimidine-2,4(1H,3H)-dione (N-5):
• b) treatment of the intermediate N-5 with hydrochloric acid in a solvent selected among ethanol, methanol, isopropanol, acetone, methyl isobutyl ketone (MIBK), ethyl acetate, isopropyl acetate or a mixture thereof, to obtain the intermediate 5-bromo-1-[2-fluoro-6-(trifluoromethyl)benzyl]-6-methyl-3-[2(R)-amino-2-phenylethyl]-pyrimidine-2,4(1H,3H)-dione hydrochloride (N-4):
• c) treatment with bases of the intermediate N-4 and reaction with ethyl 4-bromobutanoate at a temperature between 30 and 55° C. to obtain the intermediate 3-[2(R) -{ethoxycarbonylpropylamino}-2-phenylethyl]-5-bromo-1-[2-fluoro-6-(trifluoromethyl)benzyl]-6-methyl-pyrimidine-2,4(1H,3H)-dione (N-3):
• d) treatment of the intermediate N-3 with a protic acid (AH) to obtain the corresponding salt (intermediate N-2):
• wherein A− is a conjugate base of the protic acid;
• e) reaction of the intermediate N-2 with 2-fluoro-3-methoxyphenylboronic acid to obtain the intermediate 3-[2(R)-{ethoxycarbonylpropyl-amino }-2-phenylethyl]-5-(2-fluoro-3-methoxyphenyl)-1[2-fluoro-6-(trifluoromethyl)benzyl]-6-methyl-pyrimidine -2,4(1H,3H)-dione (N-1):
• f) formation of the sodium salt of Elagolix by reaction of the intermediate N-1 with sodium hydroxide: