Potassium Phosphate, Tribasic → US10023592, Example 86

HRID 518306Notes

Reaction equation

HRID 518306 reaction equation
Br[C:2]1[C:3]([O:15][CH3:16])=[CH:4][C:5]([F:14])=[C:6]([NH:8][S:9]([CH2:12][CH3:13])(=[O:11])=[O:10])[CH:7]=1.[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.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]>[F:14][C:5]1[CH:4]=[C:3]([O:15][CH3:16])[C:2]([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:7][C:6]=1[NH:8][S:9]([CH2:12][CH3:13])(=[O:11])=[O:10]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 118021927N-(5-bromo-2-fluoro-4-methoxyphenyl)ethanesulfonamideHCID 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 118022248US10023592, Example 86Yield 26.6%

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 N-(5-bromo-2-fluoro-4-methoxyphenyl)ethanesulfonamide (63 mg, 0.20 mmol), the title compound of Example 46, step 2 (75 mg, 0.21 mmol), Pd(dppf)Cl2 (19 mg, 0.03 mmol) and aqueous K3PO4 (1 M, 0.5 mL, 0.5 mmol) in dioxane (3 mL) was microwaved at 100° C. for 1 h. Purification by silica gel chromatography (PE:EA=1:1 to 1:4) followed by preparative HPLC gave the title compound (25 mg, 26.3%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 8.48 (d, J=8.4 Hz, 1H), 7.72 (s, 1H), 7.69 (s, 1H), 7.58 (d, J=7.2 Hz, 1H), 7.49 (d, J=9.2 Hz, 1H), 7.25 (s, 1H), 7.04 (s, 1H), 6.85 (d, J=12.0 Hz, 1H), 6.37 (s, 1H), 3.94 (s, 3H), 3.75 (s, 3H), 3.65 (s, 3H), 3.17 (q, J=7.2 Hz, 2H), 1.46 (t, J=7.2 Hz, 3H). LCMS: 471.1 (M+H)+

Workup

  1. customPurification by silica gel chromatography (PE:EA=1:1 to 1:4)

Sources & evidence

ORD record
ord-fc0d3f56d4af4a0c8c02755858553b38
Source dataset
uspto-grants-2015_08
Patent number
US09115114B2

Reaction notes

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