Reaktion #163387

Reaktionsgleichung

K2CO3

dimethyldiazo-2-oxopropylphosphonat

1-methyl-1H-pyrazole-4-carbaldehyde

cyclopropanecarboxylic acid [1-(4-iodo-phenyl)-ethyl]amide

2-butylamine

→

(S)—N-(1-(4-((1-Methyl-1H-pyrazol-4-yl) ethynyl)phenyl]ethyl}cyclopropanecarboxamide

Lösungsmittel

water

MeOH

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe reaction is quenched by the addition of water and EtOAc
2. 2
   SonstigeThe organic layer is separated
3. 3
   Trocknendried with Na2SO4
4. 4
   Sonstigethe solvent is removed in vacuo
5. 5
   workup.STIRRINGThe reaction mixture is stirred at r.t. over night
6. 6
   Extraktionextracted with DCM
7. 7
   TrocknenThe organic layer is dried with Na2SO4
8. 8
   Sonstigethe solvent is evaporated in vacuo
9. 9
   SonstigeThe residue is purified consecutively by column chromatography (silica gel, DCM/MeOH 98:2) and HPLC (MeOH/H2O/NH3)

Vorschrift

To 100 mg (0.91 mmol) 1-methyl-1H-pyrazole-4-carbaldehyde in 1.00 mL MeOH are added 289 mg (2.09 mmol) K2CO3 and finally dropwise 349 mg (1.82 mmol) dimethyldiazo-2-oxopropylphosphonat (in 2.0 mL MeOH).The reaction mixture is stirred at r.t. over night. The reaction is quenched by the addition of water and EtOAc. The organic layer is separated, dried with Na2SO4 and the solvent is removed in vacuo. To the residue is added 286 mg (0.91 mmol) cyclopropanecarboxylic acid [1-(4-iodo-phenyl)-ethyl]amide (I52.2), 63.7 mg (0.09 mmol) bis-(triphenylphosphin)-palladiumdichlorid, 2.00 mL 2-butylamine and 2.00 mL water. The reaction mixture is stirred at r.t. over night. The mixture is diluted with water and extracted with DCM. The organic layer is dried with Na2SO4 and the solvent is evaporated in vacuo. The residue is purified consecutively by column chromatography (silica gel, DCM/MeOH 98:2) and HPLC (MeOH/H2O/NH3).

Quelle