Triethylamine → (1-Cyclopropyl-propyl)-[4-(4-methoxy-2-methyl-phenyl)-3-nitro-pyridin-2-yl]-amine

Temperatur

-78 °C

To a solution of 4-(4-methoxy-2-methyl-phenyl)-3-nitro-3H-pyridin-2-one (0.321 g, 1.23 mmol) CH2Cl2 (13 mL), was added Na2CO3 (0.317 g, 3.02 mmol). The reaction was cooled to −78° C., and trifluoromethanesulfonic anhydride (617 μL, 3.65 mmol) was added dropwise. After the addition, the reaction stirred for 15 min at −78° C., then warmed to 0° C. for 1 h. The reaction mixture was filtered and the collected solid was washed with CHCl3. The filtrate was concentrated in vacuo and dissolved in toluene (20 mL) followed by Et3N (343 μL, 2.4 mmol) and 1-cyclopropyl propyl amine HCl (0.331 g, 2.4 mmol), and heated at 130° C. overnight. The reaction was cooled and poured onto ice/H2O. The mixture was extracted with CH2Cl2, washed with H2O, brine, dried Na2SO4, filtered, and concentrated in vacuo. Purification using flash chromatography (10% EtOAc/Hexane) gave 0.220 g (54%) of (1-cyclopropyl-propyl)-[4-(4-methoxy-2-methyl-phenyl)-3-nitro-pyridin-2-yl]-amine: MS(AP) m/z 342.1 [(M+H)+, 100]. The purified intermediate was used in the following step.

1. additionAfter the addition
2. temperaturewarmed to 0° C. for 1 h
3. filtrationThe reaction mixture was filtered
4. washthe collected solid was washed with CHCl3
5. concentrationThe filtrate was concentrated in vacuo
6. dissolutiondissolved in toluene (20 mL)
7. temperatureheated at 130° C. overnight
8. temperatureThe reaction was cooled
9. additionpoured onto ice/H2O
10. extractionThe mixture was extracted with CH2Cl2
11. washwashed with H2O, brine, dried Na2SO4
12. filtrationfiltered
13. concentrationconcentrated in vacuo
14. customPurification

ORD-Eintrag

ord-8b12c8cd22d94da7aa1c43329e4e0ee2

Quelldatensatz

uspto-grants-2006_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07067658B2