Reaction #40720

Reaction equation

2-(benzo[d][1,3]dioxol-5-yl)acetic acid

thiocarbonohydrazide

thiopene-2-carbonyl chloride

NaHCO3

→

compound 2

3-((benzo[d][1,3]dioxol-5-yl)methyl)-6-(thiophen-2-yl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole

Solvents

MeOH CH2Cl2

chloride

Conditions

Workup

1. 1
   TemperatureThe mixture was cooled
2. 2
   WashThe organics were washed with water, saturated NaCl
3. 3
   Dryingdried over Na2SO4
4. 4
   Concentrationconcentrated in vacuo
5. 5
   Otheras is in the next reaction
6. 6
   Temperaturewas refluxed 5 hours
7. 7
   OtherThe excess phoshoryl chloride was removed under reduced pressure
8. 8
   workup.ADDITIONthe subsequent residue was mixed with crushed ice
9. 9
   FiltrationThe solids were filtered
10. 10
    Washwashed with water
11. 11
    Otherdried in vaciio
12. 12
    OtherPurification by reversed-phase HPLC

Procedure

As shown in FIG. 2, 2-(benzo[d][1,3]dioxol-5-yl)acetic acid (1 mmol) and thiocarbonohydrazide (1.5 mmol) were heated at 170° C. for 15 min. The mixture was cooled and taken up in 5% MeOH/CH2Cl2 and saturated NaHCO3. The organics were washed with water, saturated NaCl, dried over Na2SO4, and concentrated in vacuo. The resulting 5-((benzo[d][1,3]dioxol-5-yl)methyl)-4H-4-amino-3-mercapto-1,2,4-triazole (compound 1001) was used as is in the next reaction. Accordingly, a mixture of compound 1001 and thiopene-2-carbonyl chloride (0.176 g, 1.2 mmol) suspended in excess phoshoryl chloride (˜10 mL) was refluxed 5 hours. The excess phoshoryl chloride was removed under reduced pressure and the subsequent residue was mixed with crushed ice. The solids were filtered, washed with water, and dried in vaciio. Purification by reversed-phase HPLC produced pure 3-((benzo[d][1,3]dioxol-5-yl)methyl)-6-(thiophen-2-yl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole (compound 2).

Source