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1349902-20-0

2,3,4,5,6,7-hexahydro-4-oxo-2-thioxo-1H-CyclopentapyriMidine-1-acetic acid synthesis

3synthesis methods
-

Yield:1349902-20-0 58%

Reaction Conditions:

Stage #1: sodium glycinate;methyl 2-oxocyclopentane-1-carboxylatewith 1-methyl-pyrrolidin-2-one at 60; for 2 h;Inert atmosphere;
Stage #2: sodium thiocyanidewith chloro-trimethyl-silane at 120; for 3 h;Inert atmosphere;

Steps:

2-(4-Oxo-2-thioxo-2,3,4,5,6,7-hexahydro-1H-cyclopenta-[d]-pyrimidin-1-yl) acetic acid (1):

Methyl 2-oxocyclopentanecarboxylate (1 eq, 17.5 mmol) was added to a suspension of glycine sodium salt (1 eq, 18.0 mmol) in NMP (18 mL). The reaction mixture was stirred for 2 hours at 60°C under argon. After cooling the mixture to room temperature, sodium thiocyanate (1.4 eq, 25 mmol) was added. Chlorotrimethylsilane (3.5 eq, 61.5 mmol) was then added dropwise and the reaction was stirred at 120° C for 3 hours. The reaction was cooled to 90° C and water (35 mL) was added. The suspension was slowly cooled to 4° C overnight and the product was collected by filtration. The product was washed with water (2 x 15 mL) and acetone (15 mL) then dried at 50° C to yield the title compound as an off white solid (1.4 g, 58%). 1H NMR (DMSO-d6) δ: 12.56 (s, 1H), 4.94 (bs, 2H), 2.85 (m, 2H), 2.59 (t, J = 7.8 Hz, 2H) 1.99 (quint, J = 7.8 Hz, 2H).

References:

Guibbal, Florian;Bénard, Sébastien;Patché, Jessica;Meneyrol, Vincent;Couprie, Jo?l;Yong-Sang, Jennyfer;Meilhac, Olivier;Jestin, Emmanuelle [Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,# 4,p. 787 - 792] Location in patent:supporting information

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