Potassium Phosphate, Tribasic → US10023592, Example 51

HRID 575558Notes

Reaction equation

HRID 575558 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][N:8]=[CH:9][CH:10]=2)[C:5](=[O:12])[N:4]([CH3:13])[CH:3]=1.[CH3:14][S:15]([NH:18][C:19]1[CH:20]=[C:21](B(O)O)[CH:22]=[CH:23][CH:24]=1)(=[O:17])=[O:16].[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]>[CH3:13][N:4]1[CH:3]=[C:2]([C:23]2[CH:24]=[C:19]([NH:18][S:15]([CH3:14])(=[O:16])=[O:17])[CH:20]=[CH:21][CH:22]=2)[C:11]2[C:6](=[CH:7][N:8]=[CH:9][CH:10]=2)[C:5]1=[O:12]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27735353-Methylsulfonylaminophenylboronic acidHCID 1180220834-Bromo-2-methyl-1,2-dihydro-2,7-naphthyridin-1-one

Product 1

HCID 118021979US10023592, Example 51Yield 69.8%

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-2,7-naphthyridin-1-one (50 mg, 0.21 mmol), [3-(methanesulfonamido)phenyl]boronic acid (68 mg, 0.31 mmol), Pd(dppf)Cl2 (15.3 mg, 0.021 mmol) and aqueous K3PO4 (1 M, 0.3 mL, 0.3 mmol) in dioxane (3 mL) was microwaved at 90° C. for 40 min. Purification by silica gel chromatography (PE:EA=100:1 to 1:1) followed by preparative HPLC gave the title compound (48.1 mg, 69.8%) as a white solid. 1H NMR (400 MHz, Methanol-d4) δ 9.56 (s, 1H), 8.68 (d, J=6.4 Hz, 1H), 7.96 (s, 1H), 7.81 (d, J=6.4 Hz, 1H), 7.51 (t, J=7.6 Hz, 1H), 7.37 (d, J=2.0 Hz, 1H), 7.34 (d, J=1.6 Hz, 1H), 7.26 (d, J=7.6 Hz, 1H), 3.71 (s, 3H), 3.03 (s, 3H). LCMS: 330.0 (M+H)+

Workup

  1. customwas microwaved at 90° C. for 40 min
  2. customPurification by silica gel chromatography (PE:EA=100:1 to 1:1)

Sources & evidence

ORD record
ord-90d8d63846e940b797797836144492da
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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