Triethylamine → diethyl {1-[(1-ethyl-1H-pyrazol-5-yl)amino]propylidene}propanedioate

温度

90 °C

5-Amino-1-ethylpyrazole (5.85 g, 0.0526 moles, 1.06 equivalents) was added in one portion to 31.35 g of a solution at room temperature, wherein the solution is of diethyl (1-chloro-1-propen-1-yl)propanedioate and/or diethyl (1-chloropropylidene)propanedioate (about 11.65 g, 0.0496 moles, 1.0 equivalent) in toluene (about 19.70 g). Triethylamine (14 ml, 10.05 g, 0.0993 moles, 2.0 equivalents) was added slowly to the reaction mixture ensuring Tint<30° C. by use of an ice bath. The reaction mixture was then heated at 90° C. for approximately 15.5 hours and then was allowed to cool to room temperature. The reaction mixture was filtered, the filter cake washed with toluene (23 ml), and then the filter cake was pulled dry. Toluene (12 ml) was added to the filtrate, and the solution was concentrated in vacuo to about 55 ml volume. Toluene (12 ml) was added to the solution which was then concentrated down to about 55 ml, and this toluene (12 ml) addition and evaporation was repeated. The toluene solution (about 55 ml) washed with 2M aqueous sodium hydroxide solution (55 ml), and the two layers were separated. The organic layer was concentrated to dryness to yield diethyl {1-[(1-ethyl-1H-pyrazol-5-yl)amino]propylidene}propanedioate as a brown liquid (11.11 g, about 72% theory yield). HPLC (5 min generic solvent gradient): TRET about 3.05. Mass Spectrum: Found: MH+ 310.1, (M-H)− 308.1.

1. custom<30° C.
2. temperatureto cool to room temperature
3. filtrationThe reaction mixture was filtered
4. washthe filter cake washed with toluene (23 ml)
5. customthe filter cake was pulled dry
6. additionToluene (12 ml) was added to the filtrate
7. concentrationthe solution was concentrated in vacuo to about 55 ml volume
8. additionToluene (12 ml) was added to the solution which
9. concentrationwas then concentrated down to about 55 ml
10. additionthis toluene (12 ml) addition and evaporation
11. washThe toluene solution (about 55 ml) washed with 2M aqueous sodium hydroxide solution (55 ml)
12. customthe two layers were separated
13. concentrationThe organic layer was concentrated to dryness
14. customto yield

ORDレコード

ord-95c93b3e17654d659c582b8eda0a5c42

出典データセット

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08003663B2