Potassium Phosphate, Tribasic → US10023592, Example 174

HRID 575663Notes

Reaction equation

HRID 575663 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([F:12])[CH:10]=2)[C:5](=[O:13])[N:4]([CH3:14])[CH:3]=1.[CH:15]1([CH2:18][O:19][C:20]2[CH:25]=[CH:24][C:23]([S:26]([CH2:29][CH3:30])(=[O:28])=[O:27])=[CH:22][C:21]=2B2OC(C)(C)C(C)(C)O2)[CH2:17][CH2:16]1.[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]>[CH:15]1([CH2:18][O:19][C:20]2[CH:25]=[CH:24][C:23]([S:26]([CH2:29][CH3:30])(=[O:28])=[O:27])=[CH:22][C:21]=2[C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([F:12])[CH:10]=3)[C:5](=[O:13])[N:4]([CH3:14])[CH:3]=2)[CH2:16][CH2:17]1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 896575182-[2-(Cyclopropylmethoxy)-5-(ethylsulfonyl)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 1180215214-Bromo-6-fluoro-2-methylisoquinolin-1-one

Product 1

HCID 118023004US10023592, Example 174Yield 16%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
70 °C

Procedure

A mixture of 4-bromo-6-fluoro-2-methylisoquinolin-1-one (500.00 mg, 1.95 mmol), 2-[2-(cyclopropylmethoxy)-5-ethylsulfonylphenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.07 g, 2.92 mmol), K3PO4 (1.24 g, 5.85 mmol) and Pd(dppf)Cl2 (0.1 g, cat.) in dioxane/H2O (30 mL/4 mL) was stirred at 70° C. for 12 hrs under Ar. The mixture was concentrated and the residue purified by column chromatography (PE:EA=1:1) to give a pink solid. The pink solid was further purified by column chromatography (DCM:EA=4:1) to afford the title compound (0.13 g, 16%) as a light yellow solid. 1H NMR (CDCl3, 400 MHz) δ 8.54 (brs, 1H), 7.96 (dd, J1=8.8 Hz, J2=2.4 Hz, 1H), 7.81 (d, J=2.0 Hz, 1H), 7.22-7.20 (m, 1H), 7.15-7.13 (m, 1H), 7.1 (d, J=8.8 Hz, 1H), 6.78 (dd, J1=10.4 Hz, J2=2.4 Hz, 1H), 3.90 (t, J=7.6 Hz, 2H), 3.68 (s, 3H), 3.15 (q, J=7.6 Hz, 2H), 1.33 (t, J=7.6 Hz, 3H), 1.06-1.02 (m, 1H), 0.50-0.43 (m, 2H), 0.15-0.14 (m, 2H). LCMS (M+H)+=416.0 (M+1)+

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue purified by column chromatography (PE:EA=1:1)
  3. customto give a pink solid
  4. customThe pink solid was further purified by column chromatography (DCM:EA=4:1)

Sources & evidence

ORD record
ord-ce6652ebf1bf4b8caf37b8c8c870329f
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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