Reaktion #92468

Reaktionsgleichung

4-Bromo-1-methyl-1H-pyrazol-3-amine

cesium carbonate

N-(2′,4′-difluoro-5-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazol-1-yl)-[1,1′-biphenyl]-3-yl)cyclopropanesulfonamide

N2

→

crude residue

Ausbeute 27.0%

N-(5-(5-(3-amino-1-methyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-1-yl)-2′,4′-difluoro-[1,1′-biphenyl]-3-yl)cyclopropanesulfonamide

Ausbeute 27.0%

Lösungsmittel

THF EtOH Water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe mixture was degassed for another 5 min
2. 2
   Sonstigethe mixture was further degassed for 5 min
3. 3
   SonstigeThe mixture was quenched
4. 4
   Extraktionextracted as in Example 1(d)
5. 5
   workup.DISTILLATIONThe solvent was distilled off

Vorschrift

A solution of N-(2′,4′-difluoro-5-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazol-1-yl)-[1,1′-biphenyl]-3-yl)cyclopropanesulfonamide (100 mg, 0.181 mmol) in THF/EtOH/Water (5:5:2) was degassed by N2 bubbling for 5 min. 4-Bromo-1-methyl-1H-pyrazol-3-amine (35 mg, 0.19 mmol, 1.1 eq.) was added and the mixture was degassed for another 5 min. Bis(tri-tert-butylphosphine)palladium(0) (5 mg, 0.009 mmol, 0.05 eq.) and cesium carbonate (170 mg, 0.54 mmol, 3.0 eq.) were added sequentially and the mixture was further degassed for 5 min and heated at 90° C. for 16 h. The mixture was quenched and extracted as in Example 1(d). The solvent was distilled off to give the crude residue which was purified by preparative HPLC to give the product in 27% yield (25 mg). 1H NMR (300 MHz, DMSO): δ 10.3 (s, 1H) 8.79 (s, 1H), 7.95-7.92 (m, 2H), 7.77-7.07 (m, 2H), 7.59 (s, 2H), 7.53-7.47 (m, 3H), 7.29 (m, 1H), 3.75 (s, 3H), 2.91 (m, 1H), 1.5-1.49 (d, 2H), 1.30-1.26 (t, 2H), 1.03-1.01 (t, 2H); LC-MS (ESI): Calculated mass: 520.5; Observed mass: 521.0 [M+H]+ (rt: 0.676 min).

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