Acetic Acid → 3-[(3-Chloropropyl)thio]-4-methyl-5-(tetrahydro-2H-pyran-4-yl)-4H-1,2,4-triazole

HRID 1668559Notes

Reaction equation

[CH3:1][N:2]1[C:6]([CH:7]2[CH2:12][CH2:11][O:10][CH2:9][CH2:8]2)=[N:5][NH:4][C:3]1=[S:13].Br[CH2:15][CH2:16][CH2:17][Cl:18].C(O)(=O)C>C(O)C>[Cl:18][CH2:17][CH2:16][CH2:15][S:13][C:3]1[N:2]([CH3:1])[C:6]([CH:7]2[CH2:12][CH2:11][O:10][CH2:9][CH2:8]2)=[N:5][N:4]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To 4-methyl-5-(tetrahydro-2H-pyran-4-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (0.4 g, prepared in analogy to the method described in Preparation 2) in ethanol (6 ml) sodium ethanolate (0.83 ml) was carefully added with stirring followed by 1-bromo-3-chloropropane (0.30 ml). The mixture was heated at 90° C. for 1 h. Acetic acid was added at room temperature until pH=4. After elimination of the solvent under reduced pressure the residue was partitioned between aqueous NaHCO3 (saturated) and DCM. The organic layer was collected and the aqueous phase extracted twice with DCM. The combined DCM layers were concentrated and submitted to column chromatography (EtOAc—acetone gradient) to give the title compound as white solid (0.173 g).

Workup

additionwas carefully added
customAfter elimination of the solvent under reduced pressure the residue was partitioned between aqueous NaHCO3 (saturated) and DCM
customThe organic layer was collected
extractionthe aqueous phase extracted twice with DCM
concentrationThe combined DCM layers were concentrated

Sources & evidence

ORD record: ord-b72219f395234997913c64731b1a4dc8
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07989444B2

Reaction notes

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