Phosphorus oxychloride → 2-(5-Amino-1,3,4-thiadiazol-2-yl)-2-methylpropanenitrile

HRID 538640Notes

Reaction equation

HRID 538640 reaction equation
[NH2:1][NH:2][C:3]([NH2:5])=[S:4].[C:6]([C:8]([CH3:13])([CH3:12])[C:9](O)=O)#[N:7].O=P(Cl)(Cl)Cl>O1CCOCC1.Cl.C(Cl)Cl>[NH2:5][C:3]1[S:4][C:9]([C:8]([CH3:13])([CH3:12])[C:6]#[N:7])=[N:1][N:2]=1

Participants

7

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 2723789ThiosemicarbazideHCID 113670912-Cyano-2-methylpropanoic acid

Product 1

HCID 1176509032-(5-Amino-1,3,4-thiadiazol-2-yl)-2-methylpropanenitrileYield 32.7%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

300 mg (3.29 mmol) of thiosemicarbazide and 370 mg (3.27 mmol) of 2-Cyano-2-methylpropanoic acid are dissolved in dioxane (10.0 mL) and heated to 90° C. 300 μL (3.29 mmol) of POCl3 are added dropwise. The reaction is stirred at 90° C. for 1 h, cooled to RT and diluted with 1 N aq. HCl and DCM. The aq. layer is separated, 4 N aq. NaOH is added to reach pH 8 and then extracted with DCM. Then combined organic layer is washed with brine and dried. The solvent is removed under reduced pressure to afford 180 mg of 2-(5-amino[1,3,4]thiadiazol-2-yl)-2-methyl-propionitrile. Yield: 32%; ESI-MS: 169 [M+H]+; HPLC (Rt): 0.24 min (method B)

Workup

  1. temperaturecooled to RT
  2. customThe aq. layer is separated
  3. addition4 N aq. NaOH is added
  4. extractionextracted with DCM
  5. washThen combined organic layer is washed with brine
  6. customdried
  7. customThe solvent is removed under reduced pressure

Sources & evidence

ORD record
ord-53f5f61f81694070a76c07d7f6535c2a
Source dataset
uspto-grants-2014_10
Patent number
US08865744B1

Reaction notes

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