In the chemical reaction process,reaction time,type of solvent,can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product.An updated downstream synthesis route of 147118-37-4 as follows., 147118-37-4
Example 13 Preparation of 2-((4/?,6S)-6-((E)-2-(4-(4-fluorophenyl)-6-isopropyl-2-(N- methylmethylsulfonamido)pyrimidin-5-yl)vinyl)-2,2-dimethyl-1 ,3-dioxan yl)acetate, methyl ester (O) from N-(4-(4-fluorophenyl)-5-formyl-6- isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide (J) and 2-((4 ?,6S)-6- ((benzo[d]thiazol-2-ylsulfonyl)methyl)-2,2-dimethyl-1 ,3-dioxan-4-yl)acetate methyl ester (N)(N) (J) (O) N-(4-(4-fluorophenyl)-5-formyl-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide (0.35 g, I .O mmol) and 2-((4 ,6S)-6-((benzo[d]thiazol-2-ylsulfonyl)methyl)-2,2-dimethyl- 1 ,3-dioxan-4-yl)acetate methyl ester (0.45 g, 1.1 mmol) were added to 12 mL of dry THF After stirring for 10 min at 20C, the reaction mixture was cooled to -70C. At this temperature 1.5 mL of NaHMDS solution (1 M in THF, total 1.5 mmol) was added in 1 h keeping the temperature between -70 and -75C. When dosing was completed, the reaction mixture was stirred for 2h at -75C, then quenched with 10% aqueous NaHC03 (10 mL). The phases were separated. The aqueous layer was extracted with 2 x 25 mL of ethyl acetate. The combined organic phases were washed with 5% aqueous Na2C03 and concentrated under vacuum. The residue was crystallized from isopropanol to give 2-((4 ,6S)-6-((E)-2-(4-(4-fluorophenyl)-6-isopropyl-2-(N-methylmethylsulfonamido) pyrimidin-5-yl)vinyl)-2,2-dimethyl-1 ,3-dioxan-4-yl)acetate, methyl ester as a solid (Compound O, 0.34 g, 0.63 mmol, 63% yield).
The chemical industry reduces the impact on the environment during synthesis 147118-37-4, I believe this compound will play a more active role in future production and life.
Reference:
Patent; DSM SINOCHEM PHARMACEUTICALS NETHERLANDS B.V.; DE LANGE, Ben; RIEBEL, Peter, Hans; WOLBERG, Michael; HEEMSKERK, Dennis; MINK, Daniel; WO2012/98048; (2012); A1;,
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