Nitrogen → 4-[5-(ethylsulfonyl)-2-methoxyphenyl]-2-methyl-6-(1-methyl-1H-pyrazol-4-yl)isoquinolin-1(2H)-one

HRID 518302Notes

Reaction equation

HRID 518302 reaction equation
N#N.Br[C:4]1[CH:9]=[C:8]([S:10]([CH2:13][CH3:14])(=[O:12])=[O:11])[CH:7]=[CH:6][C:5]=1[O:15][CH3:16].[CH3:17][N:18]1[CH:27]=[C:26](B2OC(C)(C)C(C)(C)O2)[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([C:37]3[CH:38]=[N:39][N:40]([CH3:42])[CH:41]=3)[CH:24]=2)[C:19]1=[O:43].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.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]>[CH2:13]([S:10]([C:8]1[CH:7]=[CH:6][C:5]([O:15][CH3:16])=[C:4]([C:26]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:37]4[CH:38]=[N:39][N:40]([CH3:42])[CH:41]=4)[CH:24]=3)[C:19](=[O:43])[N:18]([CH3:17])[CH:27]=2)[CH:9]=1)(=[O:12])=[O:11])[CH3:14]

Participants

8

Reactant 4

HCID 947NitrogenHCID 62657Potassium Phosphate, TribasicHCID 109788092-Bromo-4-ethylsulfonyl-1-methoxybenzeneHCID 1237513492-Methyl-6-(1-methylpyrazol-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-1-one

Product 1

HCID 1180214764-[5-(ethylsulfonyl)-2-methoxyphenyl]-2-methyl-6-(1-methyl-1H-pyrazol-4-yl)isoquinolin-1(2H)-oneYield 55.7%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

For 5 min N2 was bubbled into a mixture of 2-bromo-4-ethylsulfonyl-1-methoxybenzene (300 mg, 1.07 mmol), the title compound of Example 46, step 2 (300 mg, 0.82 mmol), K3PO4 (435.6 mg, 2.05 mmol) and Pd(dppf)Cl2 (120.2 mg, 0.16 mmol) in dioxane (8 mL) and water (0.8 mL) which was then microwaved at 110° C. for 30 min. Purification by silica gel chromatography (DCM:MeOH=100:0 to 20:1) gave the title compound (200 mg, 55.7%) as a yellow solid. 1H NMR (CDCl3, 400 MHz) δ 8.51 (d, J=8.4 Hz, 1H), 8.03 (dd, J1=8.8 Hz, J2=2.8 Hz, 1H), 7.86 (d, J=2.4 Hz, 1H), 7.72 (s, 1H), 7.64 (s, 1H), 7.63-7.61 (m, 1H), 7.19 (d, J=8.8 Hz, 1H), 7.15 (d, J=1.2 Hz, 1H), 7.09 (s, 1H), 3.97 (s, 3H), 3.85 (s, 3H), 3.68 (s, 3H), 3.18 (q, J=7.6 Hz, 2H), 1.35 (t, J=7.6 Hz, 3H). LCMS: 438.1 (M+H)+

Workup

  1. customPurification by silica gel chromatography (DCM:MeOH=100:0 to 20:1)

Sources & evidence

ORD record
ord-1cdc7bcaa2cf4ee58cb650c1ee5d6337
Source dataset
uspto-grants-2015_08
Patent number
US09115114B2

Reaction notes

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