Réaction #2286351

Équation de réaction

(2-cyano-2-{[3,5-dichloro-4-(5-isopropyl-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-hydrazono}-acetyl)-carbamic acid ethyl ester

(2-Cyano-2-{[3,5-dichloro-4-(5-isopropyl-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-hydrazono}-acetyl)-carbamic acid ethyl ester

sodium acetate

→

2-[3,5-dichloro-4-(5-isopropyl-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carbonitrile

Rendement 51.3%

2-[3,5-Dichloro-4-(5-isopropyl-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carbonitrile

Rendement 51.3%

Solvants

acetic acid

Conditions de réaction

Traitement

1. 1
   TempératureThe reaction was cooled to 25° C.
2. 2
   workup.ADDITIONwas then poured onto water (125 mL)
3. 3
   ExtractionThe resulting orange mixture was extracted with ethyl acetate (150 mL)
4. 4
   LavageThe combined organics were washed with a saturated aqueous sodium chloride solution
5. 5
   Séchagedried with magnesium sulfate
6. 6
   workup.ADDITIONtreated with Norite neutral decolorizing carbon
7. 7
   Filtrationfiltered through celite
8. 8
   Lavagewashed with ethyl acetate
9. 9
   ConcentrationThe filtrate was concentrated under vacuum
10. 10
    AutrePurification by HPLC (10-90 acetonitrile/water with 0.1% trifluoroacetic acid over 30 min)

Mode opératoire

A solution of (2-cyano-2-{[3,5-dichloro-4-(5-isopropyl-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-hydrazono}-acetyl)-carbamic acid ethyl ester (95) (190 mg, 0.38 mmol) in glacial acetic acid (4 mL) was treated with sodium acetate (158 mg, 1.15 mmol). The resulting mixture was heated to 120° C. for 3.5 h. The reaction was cooled to 25° C. and was then poured onto water (125 mL). The resulting orange mixture was extracted with ethyl acetate (150 mL). The combined organics were washed with a saturated aqueous sodium chloride solution, dried with magnesium sulfate, treated with Norite neutral decolorizing carbon, filtered through celite and washed with ethyl acetate. The filtrate was concentrated under vacuum. Purification by HPLC (10-90 acetonitrile/water with 0.1% trifluoroacetic acid over 30 min) afforded 2-[3,5-dichloro-4-(5-isopropyl-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carbonitrile (96) (87.2 mg, 44%) as an off-white solid; ES-HRMS m/e calcd for C19H16Cl2N6O3 (M+H)+ 447.0734, found 447.0735. Exact Mass=446.0661; Molecular Weight=447.2838.

Source