Synthetic Route of 16034-48-3, A common heterocyclic compound, 16034-48-3, name is 1-Pyrazoleacetic Acid, molecular formula is C5H6N2O2, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
A solution of Example 1G and DIPEA (0.15 M and 0.43 M in DMA, respectively, 257 iL, 0.04 mmol Example 1G (1.0 equivalent) and 0.12 mmol DIPEA (3.0 equivalents)),HATU (0.2 M in DMA, 257 iL, 0.052 mmol, 1.3 equivalents), and 2-(1H-pyrazol-1-yl)acetic acid (0.40 M in DMA, 121 iL, 0.048 mmol, 1.2 equivalents) were aspirated from their respective source vials, mixed through a perfluoroalkoxy mixing tube (0.2 mm inner diameter), and loaded into an injection loop. The reaction segment was injected into the flow reactor (Hastelloy coil, 0.75 mm inner diameter, 1.8 mL internal volume) set at 100 C, andpassed through the reactor at 180 iL min1 (10 minute residence time). Upon exiting the reactor, the reaction was loaded directly into an injection loop and purified by preparative HPLC on a Phenomenex Luna C8(2) 5 tm boA AXIA column (50 mm x 21.2 mm). A gradient of acetonitrile (A) and 0.1 % ammonium acetate in water (B) was used, at a flow rate of 30 mL/min (0-0.5 mm 5 % A, 0.5-6.5 mm linear gradient 5-60 % A, 6.5-7.0 mm lineargradient 60-100 % A, 7.0-8.9 mm 100 % A, 8.9-9.0 mm linear gradient 100-5 % A, 9.0-10 mm 5 % A) to yield the title compound (7.33 mg, 39 % yield). ?H NMR (400 MHz, DMSOd 6/D20) oe 7.76 (d, J= 2.3 Hz, 1H), 7.60 – 7.45 (m, 4H), 7.37 – 7.28 (m, 1H), 7.07 – 6.87 (m, 3H), 6.31 (t, J= 2.1 Hz, 1H), 5.82 (s, 1H), 5.00 (s, 2H), 3.93 (q, J= 6.9 Hz, 2H), 3.36 (s, 3H),1.14 (t, J= 6.9 Hz, 3H). MS (ESI) mlz 481.1 (M+Hj.
The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.
Reference:
Patent; ABBVIE INC.; SHEPPARD, George, S.; BOGDAN, Andrew; KATI, Warren, M.; PARK, Chang, H.; WANG, Le; MCDANIEL, Keith, F.; WO2015/89075; (2015); A1;,
Pyrazole – Wikipedia,
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