Sodium Bicarbonate → HCID 73057756, compound

HRID 2207331Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:9][C:10](=[O:19])[C:11]3[C:16]([CH:17]=2)=[CH:15][CH:14]=[C:13]([F:18])[CH:12]=3)=[CH:4][CH:3]=1.[CH3:20][N:21]1[CH:25]=[C:24](B2OC(C)(C)C(C)(C)O2)[CH:23]=[N:22]1.C(=O)([O-])O.[Na+]>CN(C=O)C.O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[F:18][C:13]1[CH:12]=[C:11]2[C:16]([CH:17]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([C:24]4[CH:23]=[N:22][N:21]([CH3:20])[CH:25]=4)=[CH:3][CH:4]=3)[NH:9][C:10]2=[O:19])=[CH:15][CH:14]=1

Participants

Conditions

Temperature: 40 °C

Procedure

A suspension of 3-(4-bromo-phenyl)-7-fluoro-2H-isoquinolin-1-one (159 mg, 0.50 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (114 mg, 0.55 mmol) and sodium hydrogen carbonate (50.4 mg, 0.60 mmol) in DMF (1 ml) and water (0.5 ml) is flushed with nitrogen and heated to 40° C. Then bis(triphenylphosphine)-palladium(II)-chloride (7.0 mg, 0.01 mmol) is added. The reaction mixture is heated to 80° C. and stirred at this temperature for 20 hours. The mixture is allowed to cool to room temperature and excess water is added. The resulting precipitate is filtered off and washed with water. The residue is chromatographed on a silica gel column with methanol/dichloromethane to afford 7-fluoro-3-[4-(1-methyl-1H-pyrazol-4-yl)-phenyl]-2H-isoquinolin-1-one as ochre solid; HPLC/MS 2.43 min (B), [M+H] 320;

Workup

customis flushed with nitrogen
temperatureThe reaction mixture is heated to 80° C.
temperatureto cool to room temperature
filtrationThe resulting precipitate is filtered off
washwashed with water
customThe residue is chromatographed on a silica gel column with methanol/dichloromethane

Sources & evidence

ORD record: ord-aff642c786304646ac10e7d20f197bdd
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09376433B2

Reaction notes

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