Sodium Carbonate → 8-chloro-7-(1-methyl-1H-pyrazol-5-yl)-3,4-dihydroisoquinolin-1(2H)-one

HRID 577507Notes

Reaction equation

HRID 577507 reaction equation
FC(F)(F)S(O[C:7]1[C:16]([Cl:17])=[C:15]2[C:10]([CH2:11][CH2:12][NH:13][C:14]2=[O:18])=[CH:9][CH:8]=1)(=O)=O.[CH3:21][N:22]1[C:26](B2OC(C)(C)C(C)(C)O2)=[CH:25][CH:24]=[N:23]1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.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].C(Cl)Cl>[Cl:17][C:16]1[C:7]([C:26]2[N:22]([CH3:21])[N:23]=[CH:24][CH:25]=2)=[CH:8][CH:9]=[C:10]2[C:15]=1[C:14](=[O:18])[NH:13][CH2:12][CH2:11]2

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 49129081-methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 867237348-Chloro-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl trifluoromethane-sulfonate

Product 1

HCID 867237338-chloro-7-(1-methyl-1H-pyrazol-5-yl)-3,4-dihydroisoquinolin-1(2H)-oneYield 20.2%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 8-chloro-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl trifluoromethanesulfonate (66a, 300 mg, 0.910 mmol) in DMF (5 mL) was added 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (205 mg, 0.956 mmol), PdCl2(dppf)-DCM (74.3 mg, 0.0910 mmol), and Na2CO3 (289 mg, 2.73 mmol). The reaction mixture was degassed with N2 and stirred in a sealed tube at 80° C. for 2 days. The reaction mixture was adjusted to pH 7 and purified by preparative chromatography to give 8-chloro-7-(1-methyl-1H-pyrazol-5-yl)-3,4-dihydroisoquinolin-1(2H)-one (66b, 48 mg, 20%) as an oil.

Workup

  1. customThe reaction mixture was degassed with N2
  2. custompurified by preparative chromatography

Sources & evidence

ORD record
ord-cb056f5ac3114ad297f6adcc72299e2b
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

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