Sodium Bicarbonate → HCID 67377517, compound

Participants

Reaction Conditions

Reaction Steps

As shown in step 4-v of Scheme 4, tert-butyl 4-(4-(5-(2-amino-5-bromopyridin-3-yl)-1H-tetrazol-1-yl)-2,3-difluorophenoxy)butylmethylcarbamate (Compound 1019, 554 mg, 1.00 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (250 mg, 1.20 mmol) were dissolved in 8.0 mL of DMF and 4.0 mL of saturated NaHCO3 (aq) were added. The mixture was flushed with argon gas for 1 hour and PdCl2(dppf) (43.2 mg, 53.0 mmol) was added. The reaction mixture was flushed with argon for an additional 30 minutes followed by heating to 100° C. for 1 hour. After cooling, the mixture was diluted with EtOAc (80 mL), washed with water (3×40 mL), washed with brine (40 mL), and dried over sodium sulfate. After filtration, the organics were concentrated under reduced pressure and the residue purified by silica gel chromatography (40% EtOAc/hexanes) to provide tert-butyl 4-(4-(5-(2-amino-5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)-1H-tetrazol-1-yl)-2,3-difluorophenoxy)butylmethylcarbamate (278 mg, 50% yield), which was used as is in subsequent reactions.

Provenance & Evidence