Cesium carbonate → Methyl 4-{[3-(4-chlorophenyl)-4-cyclopropyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]methyl}-3-methoxybenzenecarboxylate

HRID 536540Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([CH:14]3[CH2:16][CH2:15]3)[C:10](=[O:13])[NH:11][N:12]=2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:23][O:24][C:25]([C:27]1[CH:32]=[CH:31][C:30]([CH2:33]Br)=[C:29]([O:35][CH3:36])[CH:28]=1)=[O:26]>CC(C)=O.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]([CH:14]3[CH2:16][CH2:15]3)[C:10](=[O:13])[N:11]([CH2:33][C:30]3[CH:31]=[CH:32][C:27]([C:25]([O:24][CH3:23])=[O:26])=[CH:28][C:29]=3[O:35][CH3:36])[N:12]=2)=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 60 °C

Procedure

An amount of 800 mg (3.39 mmol) of 5-(4-chlorophenyl)-4-cyclopropyl-2,4-dihydro-3H-1,2,4-triazol-3-one (preparation as per WO 2007/134862 Example 36A) and 1.66 g (5.09 mmol) of caesium carbonate were suspended in 10 ml of acetone and admixed with 1.14 g (4.41 mmol) of methyl-4-(bromomethyl)-3-methoxybenzenecarboxylate. The mixture was stirred at 60° C. for 2 h. The suspension was diluted with water. It was extracted with twice 15 ml of ethyl acetate. The combined organic phases were dried over sodium sulphate and freed from the solvent on a rotary evaporator. Purification by flash chromatography over silica gel with elution with cyclohexane/ethyl acetate (gradient 4:1→1:1) gave 910 mg (64% of theory) of the target compound.

Workup

extractionIt was extracted with twice 15 ml of ethyl acetate
dry with materialThe combined organic phases were dried over sodium sulphate
customfreed from the solvent on a rotary evaporator
customPurification by flash chromatography over silica gel
washwith elution with cyclohexane/ethyl acetate (gradient 4:1→1:1)
customgave 910 mg (64% of theory) of the target compound

Sources & evidence

ORD record: ord-54fd9757a1754b68a4eda1695b7771d3
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08859601B2

Reaction notes

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