Reaktion #59722

Reaktionsgleichung

2-Chloromethyl-5-(4-iodophenyl)-[1,3,4]oxadiazole

Intermediate 7

2-Chloromethyl-5-(4-iodophenyl)-[1,3,4]oxadiazole

potassium iodide

methylamine

N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzamide

N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)benzamide

Intermediate 17

N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)benzamide

sodium carbonate

→

6-Methyl-4′-(5-methylaminomethyl-[1,3,4]oxadiazol-2-yl)biphenyl-3-carboxylic acid cyclopropylamide

Lösungsmittel

tetrahydrofuran

1,2 dimethoxyethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe reaction was evaporated to dryness in vacuo
2. 2
   Sonstigethe product was purified on a 10 g silica SPE cartridge (stepped solvent gradient 80:20 ethyl acetate:cyclohexane, 100% ethyl acetate, 95:5 ethyl acetate:methanol)
3. 3
   TemperaturThe reaction was heated under nitrogen at 80° C. for 18 hours
4. 4
   SonstigeThe solvent was removed in vacuo
5. 5
   Sonstigethe residue was purified by silica biotage chromatography
6. 6
   Wascheneluting with 95:5 ethyl acetate

Vorschrift

2-Chloromethyl-5-(4-iodophenyl)-[1,3,4]oxadiazole (Intermediate 7) (48 mg, 0.15 mmol) and potassium iodide (25 mg, 0.15 mmol) were dissolved in 2M methylamine in tetrahydrofuran (2 ml) and stirred for 18 hours at 20° C. The reaction was evaporated to dryness in vacuo and the product was purified on a 10 g silica SPE cartridge (stepped solvent gradient 80:20 ethyl acetate:cyclohexane, 100% ethyl acetate, 95:5 ethyl acetate:methanol). The resulting material was dissolved in 1,2 dimethoxyethane (4 ml) with tetrakis(triphenylphosphine)palladium(0) (16 mg, 0.014 mmol), N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzamide (Intermediate 17) (0.15 mmol) and 1M aqueous sodium carbonate (0.15 ml, 0.15 mmol). The reaction was heated under nitrogen at 80° C. for 18 hours. The solvent was removed in vacuo and the residue was purified by silica biotage chromatography eluting with 95:5 ethyl acetate:methanol.

Quelle