Benzo-1,3-dioxole-5-acetic acid → 3-((Benzo[d][1,3]dioxol-5-yl)methyl)-6-(thiophen-2-yl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole

HRID 1672498

Reaction equation

HRID 1672498 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH2:10][C:11](O)=O)=[CH:9][C:4]=2[O:3][CH2:2]1.[NH2:14][NH:15][C:16]([NH:18][NH2:19])=[S:17].C([O-])(O)=O.[Na+].[S:25]1[CH:29]=[CH:28][CH:27]=[C:26]1[C:30](Cl)=O>CO.C(Cl)Cl.[Cl-]>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH2:10][C:11]3[N:18]4[C:16]([S:17][C:30]([C:26]5[S:25][CH:29]=[CH:28][CH:27]=5)=[N:19]4)=[N:15][N:14]=3)=[CH:9][C:4]=2[O:3][CH2:2]1

Participants

7

Reactant 4

HCID 76115Benzo-1,3-dioxole-5-acetic acidHCID 789282-Thiophenecarbonyl chlorideHCID 516892Sodium BicarbonateHCID 2724189Thiocarbohydrazide

Product 1

HCID 167360613-((Benzo[d][1,3]dioxol-5-yl)methyl)-6-(thiophen-2-yl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole

Reagents, catalysts & solvents 2

HCID 312ChlorideSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
170 °C

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 vacuo. 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).

Workup

  1. temperatureThe mixture was cooled
  2. washThe organics were washed with water, saturated NaCl
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customas is in the next reaction
  6. temperaturewas refluxed 5 hours
  7. customThe excess phoshoryl chloride was removed under reduced pressure
  8. additionthe subsequent residue was mixed with crushed ice
  9. filtrationThe solids were filtered
  10. washwashed with water
  11. customdried in vacuo
  12. customPurification by reversed-phase HPLC

Sources & evidence

ORD record
ord-115d2a5b2be3403c8c4554bf47631361
Source dataset
uspto-grants-2011_08
Patent number
US07998987B2

Linked notes

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