2-Bromopyridine → 2-Methyl-6-pyridin-2-ylisoquinolin-1-one

HRID 575578Notes

Reaction equation

HRID 575578 reaction equation
[CH3:1][N:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7](B3OC(C)(C)C(C)(C)O3)[CH:8]=2)[C:3]1=[O:21].Br[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=1.C([O-])(O)=O.[Na+]>CS(C)=O.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]>[CH3:1][N:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=3)[CH:8]=2)[C:3]1=[O:21]

Participants

6

Reactant 3

HCID 79732-BromopyridineHCID 516892Sodium BicarbonateHCID 1212288342-Methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-dihydroisoquinolin-1-one

Product 1

HCID 1180222082-Methyl-6-pyridin-2-ylisoquinolin-1-oneYield 46.1%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

A mixture of 2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-1-one (420 mg, 1.47 mmol), 2-bromopyridine (698 mg, 4.42 mmol), Pd(dppf)Cl2 (107 mg, 0.15 mmol) and saturated aqueous NaHCO3 (3.5 mL) in DMSO (25 mL) was microwaved at 150° C. for 45 min. After extractive work up with ethyl acetate, purification by silica gel chromatography (PE:EA=3:1 to 3:2) gave the title compound (160 mg, 46.0%) as a white solid. 1H NMR (CDCl3, 400 MHz) δ 8.76 (d, J=4.8 Hz, 1H), 8.53 (d, J=8.0 Hz, 1H), 8.20 (d, J=1.2 Hz, 1H), 8.07 (dd, J1=8.4 Hz, J2=1.6 Hz, 1H), 7.85-7.82 (m, 2H), 7.34-7.30 (m, 1H), 7.11 (d, J=7.2 Hz, 1H), 6.6 (d, J=7.2 Hz, 1H), 3.64 (s, 3H). LCMS: 237.2 (M+H)+

Workup

  1. customwas microwaved at 150° C. for 45 min
  2. customAfter extractive work up with ethyl acetate, purification by silica gel chromatography (PE:EA=3:1 to 3:2)

Sources & evidence

ORD record
ord-b23bd43242464c37a474338ce9807287
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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