Potassium Phosphate, Tribasic → US10023592, Example 72

HRID 518295Notes

Reaction equation

HRID 518295 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]3[CH:13]=[N:14][C:15]([CH3:18])=[CH:16][CH:17]=3)[CH:10]=2)[C:5](=[O:19])[N:4]([CH3:20])[CH:3]=1.[CH2:21]([S:23]([NH:26][C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[CH:31][CH:32]=1)(=[O:25])=[O:24])[CH3:22].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:20][N:4]1[CH:3]=[C:2]([C:31]2[CH:32]=[C:27]([NH:26][S:23]([CH2:21][CH3:22])(=[O:24])=[O:25])[CH:28]=[CH:29][CH:30]=2)[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]3[CH:13]=[N:14][C:15]([CH3:18])=[CH:16][CH:17]=3)[CH:10]=2)[C:5]1=[O:19]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 467388243-(Ethylsulfonamido)phenylboronic acidHCID 1180216054-Bromo-2-methyl-6-(6-methylpyridin-3-yl)isoquinolin-1-one

Product 1

HCID 118021553US10023592, Example 72Yield 14.1%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 4-bromo-2-methyl-6-(6-methylpyridin-3-yl)isoquinolin-1-one (135 mg, 0.41 mmol), [3-(ethylsulfonylamino)phenyl]boronic acid (141 mg, 0.62 mmol), Pd(dppf)Cl2 (35 mg, 0.05 mmol) and aqueous 1M K3PO4 (1.03 mL) in dioxane (6 mL) was microwaved at 100° C. for 1 h. Purification by silica gel chromatography (PE:EA=3:1 to 1:2) followed by preparative HPLC gave the title compound (25 mg, 14.1%) as a white solid. 1H NMR (CDCl3, 400 MHz) δ 8.74 (d, J=2.0 Hz, 1H), 8.41 (d, J=8.4 Hz, 1H), 7.96 (d, J=8.0 Hz, 1H), 7.86 (d, J=8.8 Hz, 1H), 7.75 (s, 1H), 7.58 (s, 1H), 7.47 (t, J=8.0 Hz, 1H), 7.39 (s, 1H), 7.35 (d, J=8.4 Hz, 1H), 7.30 (d, J=8.4 Hz, 1H), 7.24 (d, J=8.4 Hz, 1H), 3.59 (s, 3H), 3.59 (s, 3H), 3.15 (q, J=7.2 Hz, 2H), 1.19 (t, J=7.2 Hz, 3H). LCMS: 434.1 (M+H)+.

Workup

  1. customwas microwaved at 100° C. for 1 h
  2. customPurification by silica gel chromatography (PE:EA=3:1 to 1:2)

Sources & evidence

ORD record
ord-53669018941e47869061436f3f6591cd
Source dataset
uspto-grants-2015_08
Patent number
US09115114B2

Reaction notes

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