Réaction #46259

Équation de réaction

N,N′-diisopropylethylamine

3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-2-oxo-propionic acid ethyl ester

thiosemicarbazide

EtOH

→

title compound

2-(5-oxo-3-thioxo-2,3,4,5-tetrahydro-[1,2,4]triazin-6-ylmethyl)-indan-1,3-dione

Conditions de réaction

Traitement

1. 1
   Températureheated to 40° C. for 6 h
2. 2
   ConcentrationThe reaction mixture was concentrated in vacuo and solid
3. 3
   Autrewas triturated with hot EtOH/EtOAc
4. 4
   Filtrationfiltered
5. 5
   Lavagewashed with EtOAc
6. 6
   AutreThe solid was dried overnight in a vacuum oven (40° C.)

Mode opératoire

A slurry of 3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-2-oxo-propionic acid ethyl ester (20 g, 76.6 mmol) in anhydrous EtOH (300 mL) was charged with thiosemicarbazide (6.98 g, 76.6 mmol) in one portion and heated to 80° C. for 2 h. The reaction mixture was charged with N,N′-diisopropylethylamine (DIEA) (26.7 mL, 76.56 mmol) and heated to 40° C. for 6 h then stirred at rt for an additional 10 h. The reaction mixture was concentrated in vacuo and solid was triturated with hot EtOH/EtOAc filtered and washed with EtOAc. The solid was dried overnight in a vacuum oven (40° C.) resulting in the title compound as an off-white solid; 1H NMR (DMSO-d6, 400 MHz) δ 4.68 (s, 2H), 7.85-7.95 (m, 4H); MS (ES+): m/z 289.2 (100) [MH+], HPLC: tR=2.50 min (MicromassZQ, polar—5 min).

Source