Potassium Phosphate, Tribasic → HCID 67540669, compound

HRID 1192321Notes

Reaction equation

HRID 1192321 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][CH:6]=[CH:5]2.BrC1C=CC(C=O)=CC=1.[C:21]([N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1)([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1>COCCOC.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:24]([O:23][C:21]([N:28]1[CH2:33][CH2:32][N:31]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[CH:8]=[N:7][CH:6]=[CH:5]3)[CH2:30][CH2:29]1)=[O:22])([CH3:27])([CH3:25])[CH3:26]

Participants

8

Reactant 5

HCID 62657Potassium Phosphate, TribasicHCID 707414-BromobenzaldehydeHCID 143452tert-Butyl piperazine-1-carboxylateHCID 3136816-BromoisoquinolineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl

Product 1

HCID 67540669HCID 67540669, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

A round bottom flask charged with 6-bromo isoquinoline (prepared from 4-bromobenzaldehyde according to the literature: Neiko Nerenz, et al. (1998) J. Chem. Soc. Perkin Trans. 2, 437-447, 0.200 g, 0.961 mmol), 1-Boc piperazine (0.215 g, 1.15 mmol), K3PO4 (0.286 g, 1.35 mmol), (2′-dicyclohexylphosphanyl-biphenyl-2-yl)-dimethylamine (0.028 g, 0.072 mmol) and Pd2dba3 (0.022 g, 0.024 mmol) in dry DME (2 mL) was purged under N2 and heated at reflux for 5 hours. After cooling, the mixture was partitioned between EtOAc and H2O. The organic layer was washed with brine, dried and concentrated. The residue was purified by column chromatography (1:1 hexanes/EtOAc,) to give 4-Isoquinolin-6-yl-piperazine-1-carboxylic acid tert-butyl ester (0.210 g, 70%) as a white solid. 1H NMR (CDCl3, 400 MHz) δ 9.04 (s, 1H), 8.39 (dd, J=6.8 Hz, J=2.8 Hz, 1H), 7.83 (dd, J=9.2 Hz, J=2.8 Hz, 1H), 7.45 (d, J=6.8 Hz, 1H), 7.32 (dd, J=9.2 Hz, J=2.4 Hz, 1H), 6.98 (s, 1H), 3.64 (m, 4H), 3.35 (m, 4H), 1.50 (s, 9H). LCMS (APCI+) m/z 314 [M+H]+; Rt=2.14 minutes.

Workup

  1. temperatureheated
  2. temperatureat reflux for 5 hours
  3. temperatureAfter cooling
  4. customthe mixture was partitioned between EtOAc and H2O
  5. washThe organic layer was washed with brine
  6. customdried
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography (1:1 hexanes/EtOAc,)

Sources & evidence

ORD record
ord-5968c5fdc2fc4391b22449a7c8bf384e
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

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