Sodium Bicarbonate → US10023592, Example 46

HRID 575552Notes

Reaction equation

HRID 575552 reaction equation
Br[C:2]1[CH:7]=[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])[CH:5]=[CH:4][C:3]=1[O:12][CH2:13][CH:14]1[CH2:16][CH2:15]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].C([O-])(O)=O.[Na+]>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:14]1([CH2:13][O:12][C:3]2[CH:4]=[CH:5][C:6]([S:8]([CH3:11])(=[O:10])=[O:9])=[CH:7][C:2]=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)[CH2:16][CH2:15]1

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 1180216932-Bromo-1-(cyclopropylmethoxy)-4-(methylsulfonyl)benzeneHCID 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 118022366US10023592, Example 46Yield 34.9%

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 2-bromo-1-(cyclopropylmethoxy)-4-methanesulfonylbenzene (20.8 mg, 0.068 mmol), 2-methyl-6-(1-methylpyrazol-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-1-one (30 mg, 0.08 mmol), NaHCO3 (14.28 mg, 0.17 mmol), and Pd(dppf)Cl2 (10 mg, 0.014 mmol) in dioxane (2.0 mL) and H2O (0.5 mL) was microwaved under N2 at 100° C. for 30 min. Purification by preparative HPLC gave the title compound (11 mg, 28%) as a white solid. 1H NMR (CDCl3, 400 MHz) δ 8.48 (d, J=8.4 Hz, 1H), 7.98-8.04 (m, 1H), 7.89 (d, J=2.4 Hz, 1H), 7.68 (s, 1H), 7.63 (s, 1H), 7.58-7.62 (m, 1H), 7.19-7.21 (m, 1H), 7.11-7.15 (m, 1H), 7.09 (s, 1H), 3.93 (s, 3H), 3.83-3.91 (m, 2H), 3.66 (s, 3H), 3.12 (s, 3H), 0.94-1.04 (m, 1H), 0.30-0.40 (m, 2H), 0.00-0.12 (m, 2H). LCMS: 464.1 (M+H)+

Workup

  1. customwas microwaved under N2 at 100° C. for 30 min
  2. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-2969caaa90494b0291945a48e86bdd8b
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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