Sodium Carbonate → HCID 66608768, compound

HRID 709952Notes

Reaction equation

HRID 709952 reaction equation
[NH2:1][C@H:2]([C:4]1[N:5]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:6](=[O:15])[C:7]2[C:12]([CH:13]=1)=[CH:11][CH:10]=[CH:9][C:8]=2Cl)[CH3:3].[CH3:22][N:23]1[CH:27]=[C:26](B(O)O)[CH:25]=[N:24]1.C([O-])([O-])=O.[Na+].[Na+]>CC(N(C)C)=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]>[NH2:1][C@H:2]([C:4]1[N:5]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:6](=[O:15])[C:7]2[C:12]([CH:13]=1)=[CH:11][CH:10]=[CH:9][C:8]=2[C:26]1[CH:25]=[N:24][N:23]([CH3:22])[CH:27]=1)[CH3:3]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 112635011-Methyl-1H-pyrazole-4-boronic acidHCID 66607319(S)-3-(1-aminoethyl)-8-chloro-2-phenylisoquinolin-1(2H)-one

Product 1

HCID 66608768HCID 66608768, compoundYield 85.8%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

To a mixture of (S)-3-(1-aminoethyl)-8-chloro-2-phenylisoquinolin-1(2H)-one (1) (1.0 g, 3.35 mmol) and 1-methyl-1 h-pyrazole-4-boronic acid (815 mg, 5.02 mmol) in anhydrous DMA (10 mL) in a sealed tube, PdCl2(dppf) (219 mg, 0.27 mmol) and aqueous Na2CO3 solution (1 M, 10.0 mL, 10.0 mmol) were added and the resulting mixture was stirred at 120° C. for 3 h. The reaction mixture was allowed to cool to RT, quenched with water, and then extracted with ethyl acetate (200 mL×3). The combined organic layers were washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by ISCO (silica gel cartridge, 0-8% MeOH-DCM) to afford the product, (S)-3-(1-aminoethyl)-8-(1-methyl-1H-pyrazol-4-yl)-2-phenylisoquinolin-1(2H)-one (63) (990 mg, 85% yield) as a pink/magenta solid. ESI-MS m/z: 345.2 [M+H]+.

Workup

  1. temperatureto cool to RT
  2. customquenched with water
  3. extractionextracted with ethyl acetate (200 mL×3)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. customthe residue was purified by ISCO (silica gel cartridge, 0-8% MeOH-DCM)

Sources & evidence

ORD record
ord-b46f5b5f69774a8fb4dd8b127bd7f668
Source dataset
uspto-grants-2015_11
Patent number
US09181221B2

Reaction notes

Loading…