Nitrogen → US10023592, Example 87

HRID 575580Notes

Reaction equation

HRID 575580 reaction equation
N#N.Br[C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)[CH:12]=2)[C:7](=[O:20])[N:6]([CH3:21])[CH:5]=1.[CH2:22]([S:24]([NH:27][C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=1)(=[O:26])=[O:25])[CH3:23].[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]>[CH3:21][N:6]1[CH:5]=[C:4]([C:32]2[CH:33]=[C:28]([NH:27][S:24]([CH2:22][CH3:23])(=[O:25])=[O:26])[CH:29]=[CH:30][CH:31]=2)[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)[CH:12]=2)[C:7]1=[O:20]

Participants

7

Reactant 4

HCID 947NitrogenHCID 62657Potassium Phosphate, TribasicHCID 467388243-(Ethylsulfonamido)phenylboronic acidHCID 1180220374-Bromo-2-methyl-6-pyridin-2-ylisoquinolin-1-one

Product 1

HCID 118022657US10023592, Example 87Yield 3.9%

Reagents, catalysts & solvents 2

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

Procedure

For 5 min, N2 was bubbled through a mixture of 4-bromo-2-methyl-6-pyridin-2-ylisoquinolin-1-one (48.1 mg, 0.153 mmol), [3-(ethylsulfonylamino)phenyl]boronic acid (35.0 mg, 0.153 mmol), Pd(dppf)Cl2 (22.3 mg, 0.03 mmol) and aqueous 1M K3PO4 (0.38 mL, 0.38 mmol, 1 M) in dioxane (5 mL) which was then microwaved at 80° C. for 20 min. Purification by silica gel chromatography (PE:EA=3:1 to 1:2) followed by preparative HPLC gave the title compound (2.5 mg, 3.9%) as a white solid. 1H NMR (Methanol-d4, 400 MHz) δ 8.69 (d, J=8.4 Hz, 1H), 8.59 (d, J=8.4 Hz, 1H), 8.23 (d, J=1.2 Hz, 1H), 8.15-8.22 (m, 1H), 8.10 (dd, J1=8.4 Hz, J2=1.6 Hz, 2H), 7.65-7.62 (m, 1H), 7.50-7.45 (m, 3H), 7.38-7.30 (m, 2H), 3.71 (s, 3H), 3.16 (q, J=7.2 Hz, 2H), 1.32 (t, J=7.2 Hz, 3H). LCMS: 420.1 (M+H)+

Workup

  1. customwas then microwaved at 80° C. for 20 min
  2. customPurification by silica gel chromatography (PE:EA=3:1 to 1:2)

Sources & evidence

ORD record
ord-e941ab7ccf8545ad8c2059ce4bb68284
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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