Trifluoroacetic acid → 5-Chloro-3-nitro-4-[4-(1,2,4-oxadiazol-3-ylmethyl)-1-piperazinyl]-2-pyridinamine

To a solution of tert-butyl 4-((1,2,4-oxadiazol-3-yl)methyl)piperazine-1-carboxylate (213 mg, 0.790 mmol) in CH2Cl2 (18 mL) was added TFA (1.8 mL, 23.8 mmol) and the solution was stirred at room temperature for 1½ h. The reaction was concentrated in vacuo, azeotroping with toluene (×2) and dried in vacuum desiccator (containing KOH) overnight to give a yellow oil. The crude oil was dissolved in iPrOH (4.4 mL) and both 2-amino-3-nitro-4,5-dichloropyridine (190 mg, 0.752 mmol) and DIPEA (520 μl, 3.00 mmol) were added. The solution was stirred at 50° C. for 4 h. On cooling, a yellow precipitate dropped out which was filtered, washed with Et2O, dried in vacuo to yield the title compound as a yellow solid (165 mg, 0.486, 65%). The filtrate was concentrated in vacuo to give 715 mg oily yellow solid. Purification was accomplished by flash chromatography on silica gel (4×11) eluting with EtOAc/hexane (40-50%) to yield the title compound (42 mg, 16%) as a yellow solid.

1. concentrationThe reaction was concentrated in vacuo
2. customazeotroping with toluene (×2)
3. dry with materialdried in vacuum desiccator (containing KOH) overnight
4. customto give a yellow oil
5. stirringThe solution was stirred at 50° C. for 4 h
6. temperatureOn cooling
7. additiona yellow precipitate dropped out which
8. filtrationwas filtered
9. washwashed with Et2O
10. customdried in vacuo

ORD-Eintrag

ord-1e1f763256774702ad53e2da1b866cbd

Quelldatensatz

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09447092B2