Electric Literature of 7699-18-5, 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 7699-18-5 as follows.
Preparation of 5-methoxy-2-(1 -methyl-1 H-pyrazol-4-yl)-indole-3-carbaldehyde; 5-Methoxy isatin (0.2 g, 1.1 mmol, 1 eq.) was dissolved in hydrazine hydrate (1.2 ml_, 38 mmol, 34 eq.) and refluxed for 15 minutes. The reaction mixture was poured into cold water and extracted with EtOAc. The combined organic extracts were dried on Na2SO4. The solvent was evaporated to afford crude 5-methoxy-1 ,3-dihydro-indol-2-one that was purified by silica gel column chromatography (eluent: hexane/EtOAc from 10:0 to 6:4). Yield: 27%. MS (m/z): 164.2 (MH+).Phosphorous oxybromide (0.35 ml_, 3.1 mmol, 2.5 eq.) was added drop wise to a solution of DMF (0.3 ml_, 3.7 mmol, 3 eq.) in dry methylene chloride at 00C. The mixture was stirred at 00C for 30 minutes, then a solution of 5-methoxy-1 ,3-dihydro-indol-2-one (0.2 g, 1.2 mmol, 1 eq.) in dry methylene chloride (2 ml_) was added and the mixture was refluxed for 3 hours. The solution was neutralized with solid NaHCO3 and extracted with methylene chloride. The organic layer was dried on Na2SO4 and evaporated under reduced pressure. The crude mixture was purified by silica gel column chromatography (eluent: hexane/AcOEt 6:4 to 4:6) to give pure 2-bromo-5-methoxy-indole-3-carbaldehyde. Yield: 45%. MS (m/z): 254.1 (MH+). A stirred solution of 2-bromo-5-methoxy-indole-3-carbaldehyde (2.0 g, 7.9 mmol, 1 eq.) in DME (2 ml_) was deoxygenated by bubbling argon for 10 minutes at rt. Pd(PPh3)4 (0.9 g, 0.8 mmol, 0.1 eq.) was added followed by a solution of 1-methyl-4-(4,4,5,5-tetramethyl- [1 ,3,2]dioxaborolan-2-yl)-1 H-pyrazole (2.4 g, 1 1.63 mmol, 1.48 eq.) in ethanol (2.5 ml_). 2M Na2CO3 (33 ml_, 8.5 eq.) was also deoxygenated with argon and added. The resulting mixture was heated at 78C for 18 hours. The reaction mixture was cooled to room temperature, quenched with water, and extracted with methylene chloride. Organic layer was dried on anhydrous Na2SO4 and evaporated under reduced pressure to give the crude product 1f. Yield: 89%. MS (m/z): 256.1 (MH+).
According to the analysis of related databases, 7699-18-5, the application of this compound in the production field has become more and more popular.
Reference:
Patent; WYETH LLC; AYRAL-KALOUSTIAN, Semiramis; MANSOUR, Tarek Suhayl; TSOU, Hwei-Ru; ZHANG, Nan; VENKATESAN, Aranapakam M.; DI, Li; KERNS, Edward H.; WO2010/30727; (2010); A1;,
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