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Preparation of 2-(2-((4-fluorobenzyl)thio)-4-oxo-4,5,6,7-tetrahydro-1H-cyclopenta[d]pyrimidin-1-yl)acetic acid from 2,3,4,5,6,7-hexahydro-4-oxo-2-thioxo-1H-cyclopenta[d]pyrimidin-1-yl) as raw material and 4-fluorobenzylchloride (13.4 g, 1.05 eq) The general procedure was as follows: 2,3,4,5,6,7-hexahydro-4-oxo-2-thio-1H-cyclopentadienopyrimidin-1-yl-acetic acid was slurried in a mixture of water (112 mL) and isopropanol (20 mL). A 50.9% aqueous NaOH solution (13.82 g, 1.99 eq.) was added, followed by washing with water (10 mL) to obtain a solution. Next, Na2CO3 (1.50 g, 0.16 eq.) was added and the solution was heated to 40 ± 3°C. 4-fluorobenzyl chloride was then added and subsequently washed with isopropanol (12 mL). The reaction mixture was stirred at 40 ± 3°C until the reaction was complete (about 2.5 h). After cooling to 20 ± 3°C, formic acid (2.4 g, 0.6 eq.) was added and the product was crystallized within 30 min. a second batch of formic acid (6.9 g, 1.7 eq.) was added within 1 h. The slurry was stirred at 20 ± 3°C for at least 1 h. The reaction mixture was then stirred for at least 1 h. The product was then filtered to separate the product. The slurry was filtered to separate the product, washed twice successively with a mixture of water (32 mL) and isopropanol (8 mL), then with isopropanol (40 mL), and finally dried in vacuo at 50°C to give the title compound as an off-white solid (28.6 g, 97% yield).1H NMR (d6-DMSO) δ: 1.95 (2H, m), 2.57 (2H, t) , 2.85 (2H, t), 4.4 (2H, s), 4.7 (2H, s), 7.15 (2H, dd), 7.45 (2H, dd), ~13.6 (1H, vbrs).

[1] Patent: WO2011/146494, 2011, A1. Location in patent: Page/Page column 11
[2] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 3, p. 839 - 843
[3] Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 4, p. 787 - 792