Potassium Phosphate, Tribasic → US10023592, Example 123

HRID 518342Notes

Reaction equation

HRID 518342 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[N:9][CH:10]=2)[C:5](=[O:12])[N:4]([CH3:13])[CH:3]=1.[CH2:14]([S:16]([NH:19][C:20]1[CH:21]=[C:22](B(O)O)[CH:23]=[CH:24][CH:25]=1)(=[O:18])=[O:17])[CH3:15].[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]>[CH3:13][N:4]1[CH:3]=[C:2]([C:24]2[CH:25]=[C:20]([NH:19][S:16]([CH2:14][CH3:15])(=[O:17])=[O:18])[CH:21]=[CH:22][CH:23]=2)[C:11]2[C:6](=[CH:7][CH:8]=[N:9][CH:10]=2)[C:5]1=[O:12]

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 467388243-(Ethylsulfonamido)phenylboronic acidHCID 1180225434-Chloro-2-methyl-2,6-naphthyridin-1-one

Product 1

HCID 118022313US10023592, Example 123Yield 6.8%

Reagents, catalysts & solvents 3

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

Procedure

A mixture of 4-chloro-2-methyl-2,6-naphthyridin-1-one (50.0 mg, 0.26 mmol), [3-(ethylsulfonylamino)phenyl]boronic acid (88.0 mg, 0.38 mmol), Pd(dppf)Cl2 (15.3 mg, 0.026 mmol) and K3PO4 (190 mg, 0.9 mmol) in dioxane (3 mL) and water (0.5 mL) was microwaved at 120° C. under microwave for 2 h. Purification by silica gel chromatography on (PE:EA=10:1 to 1:1) followed by preparative HPLC gave the title compound (5.9 mg, 6.8%) as a yellow solid. 1H NMR (Methanol-d4, 400 MHz) δ 8.99 (brs, 1H), 8.71 (d, J=6.0 Hz, 1H), 8.39 (d, J=5.6 Hz, 1H), 7.62 (s, 1H), 7.51 (t, J=8.0 Hz, 1H), 7.41-7.40 (m, 1H), 7.36 (dd, J1=8.0 Hz, J2=1.2 Hz, 1H), 7.29 (d, J=5.6 Hz, 1H), 3.72 (s, 3H), 3.17 (q, J=7.6 Hz, 2H), 1.35 (t, J=7.6 Hz, 3H). LCMS: 344.1 (M+H)+.

Workup

  1. customwas microwaved at 120° C. under microwave for 2 h
  2. customPurification by silica gel chromatography on (PE:EA=10:1 to 1:1)

Sources & evidence

ORD record
ord-62f5c200196c48b78ab6728b23ad6950
Source dataset
uspto-grants-2015_08
Patent number
US09115114B2

Reaction notes

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