With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.1001180-21-7,(R)-tert-Butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate,as a common compound, the synthetic route is as follows.
A flask was equipped with a thermocouple, mechanic stirrer, a nitrogen inlet and drying tube. To the flask was added (R)-tert-buty 4-(5-methyl-7-oxo-6,7-dihydro-5H- cyclopenta[i ]pyrimidin-4-yl)piperazine-l -carboxylate (46.0 g, 139 mmol) followed by dichloromethane (1.10 L) and RuCl(TsDACH) catalyst (1.50 g, 2.80 mmol) with nitrogen degassing (gas dispersion tube) and agitation at room temperature. To the mixture was added triethylamine (23.0 mL, 167 mmol) with degassing. Formic acid (7.40 mL, 195 mmol) was slowly added to the mixture at a rate of about 1 mL/min. Good agitation with stirring was maintained until complete consumption of starting material (about 8-12 hr) as determined by HPLC analysis. The reaction was quenched with saturated sodium bicarbonate (2.00 vol., 100 mL), the layers were separated and the aqueous layer was discarded. The organic layer was washed with saturated sodium bicarbonate, saturated ammonium chloride and brine (2.00 vol., 100 mL each). The organics were dried over sodium sulfate, filtered and solvent exchanged into methanol. The methanolic solution (5.00 vol.) of crude product was charged with 50 wt % SiliaBond Thiol (Silicycle, Inc.) and 20 wt% Charcoal. The mixture was heated to about 50 C and maintained at that temperature with good stirring overnight. The mixture was cooled to room temperature, filtered over a pad of Celite and then polish filtered through a 0.45 micron filter. The mixture was distilled to a minimum working volume and concentrated under reduced pressure to afford the product (44.0 g, 95 % yield), as a 96:4 mixture of trans/cis diastereomers) as solid. Trace amount of Ru metal was measured by ICP-EOS and found that the product contained less than about 20 ppm Ru. The product was purified by preparative HPLC under the following conditionsor crystallization from ethyl acetate/heptane to yield 98.4 % pure product, 97.7 % de with about 100% ee., 1001180-21-7
The synthetic route of 1001180-21-7 has been constantly updated, and we look forward to future research findings.
Reference：
Patent; ARRAY BIOPHARMA INC.; GENENTECH, INC.; LANE, Jonathan W.; REMARCHUK, Travis; SHAKYA, Sagar; SPENCER, Keith L.; STENGEL, Peter J.; WO2013/173736; (2013); A1;,
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