Potassium Phosphate, Tribasic → US10023592, Example 128

HRID 518345Notes

Reaction equation

HRID 518345 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([N:12]3[CH:16]=[C:15]([CH3:17])[CH:14]=[N:13]3)[CH:10]=2)[C:5](=[O:18])[N:4]([CH3:19])[CH:3]=1.[CH:20]1([CH2:23][O:24][C:25]2[CH:30]=[CH:29][C:28]([S:31]([CH3:34])(=[O:33])=[O:32])=[CH:27][C:26]=2B2OC(C)(C)C(C)(C)O2)[CH2:22][CH2:21]1.[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]>[CH:20]1([CH2:23][O:24][C:25]2[CH:30]=[CH:29][C:28]([S:31]([CH3:34])(=[O:33])=[O:32])=[CH:27][C:26]=2[C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([N:12]4[CH:16]=[C:15]([CH3:17])[CH:14]=[N:13]4)[CH:10]=3)[C:5](=[O:18])[N:4]([CH3:19])[CH:3]=2)[CH2:21][CH2:22]1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 1180215704-Bromo-2-methyl-6-(4-methylpyrazol-1-yl)isoquinolin-1-oneHCID 1234348592-[2-(Cyclopropylmethoxy)-5-(methylsulfonyl)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 118022215US10023592, Example 128Yield 25.7%

Reagents, catalysts & solvents 2

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

Procedure

4-Bromo-2-methyl-6-(4-methylpyrazol-1-yl)isoquinolin-1-one (40.0 mg, 0.126 mmol), the title compound of Example 90, step 1 (53.2 mg, 0.152 mmol), Pd(dppf)Cl2 (200.0 mg, 0.05 mmol) and aqueous 1M K3PO4 (0.38 mL, 0.38 mmol) in dioxane (3 mL) were heat in a microwave at 100° C. for 1 h. Purification by preparative HPLC gave the title compound (15.0 mg, 25%) as a white solid. 1H NMR (CDCl3, 400 MHz) δ 8.57 (d, J=8.4 Hz, 1H), 8.00 (d, J=8.4 Hz, 1H), 7.90 (s, 1H), 7.75 (d, J=7.6 Hz, 1H), 7.73 (s, 1H), 7.54 (s, 1H), 7.50 (s, 1H), 7.14 (s, 1H), 7.12 (s, J=9.2 Hz, 1H), 3.96-3.83 (m, 2H), 3.68 (s, 3H), 3.13 (s, 3H), 2.15 (s, 3H), 1.01-0.94 (m, 1H), 0.38-0.28 (m, 2H), 0.08-0.02 (m, 2H). LCMS: 464.1 (M+H)+.

Workup

  1. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-2aceb1e55da8486eab88283e3a59dcff
Source dataset
uspto-grants-2015_08
Patent number
US09115114B2

Reaction notes

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