Water → 2-[6-Acetyl-1-(2-Chloro-Phenyl)-3,4-Dihydro-1H-Isoquinolin-2-Yl]-1-(4-Cyclobutyl-Piperazin-1-Yl)-Ethanone

HRID 1713087Notes

Reaction equation

HRID 1713087 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[Cl:18])[N:7]([CH2:19][C:20]([N:22]1[CH2:27][CH2:26][N:25]([CH:28]3[CH2:31][CH2:30][CH2:29]3)[CH2:24][CH2:23]1)=[O:21])[CH2:6][CH2:5]2.[CH2:32]([O:36]C=C)[CH2:33]CC.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:32]([C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[Cl:18])[N:7]([CH2:19][C:20]([N:22]1[CH2:27][CH2:26][N:25]([CH:28]3[CH2:31][CH2:30][CH2:29]3)[CH2:24][CH2:23]1)=[O:21])[CH2:6][CH2:5]2)(=[O:36])[CH3:33]

Participants

7

Reactant 4

HCID 962WaterHCID 8108Butyl vinyl etherHCID 812191,3-Bis(diphenylphosphino)propaneHCID 247512302-[6-bromo-1-(2-chloro-phenyl)-3,4-dihydro-1H-isoquinolin-2-yl]-1-(4-cyclobutyl-piperazin-1-yl)-ethanone

Product 1

HCID 247513712-[6-Acetyl-1-(2-Chloro-Phenyl)-3,4-Dihydro-1H-Isoquinolin-2-Yl]-1-(4-Cyclobutyl-Piperazin-1-Yl)-Ethanone

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 2-[6-bromo-1-(2-chloro-phenyl)-3,4-dihydro-1H-isoquinolin-2-yl]-1-(4-cyclobutyl-piperazin-1-yl)-ethanone (310 mg, 0.62 mmol) in dry DMF (5.0 ml) is added n-butylvinyl ether (310 mg, 3.98 mmol, 5.0 eq.), TEA (75 mg, 0.74 mmol, 1.2 eq.), 1,3-bis(diphenylphosphino)propane (7 mg, 0.0017 mmol, 0.0276 eq.), and palladium acetate (3.5 mg, 0.015 mmol, 0.025 eq.) under nitrogen. The resulting mixture is stirred at 80° C. for 7 hr. Water (20 ml) is added to quench the reaction, and the mixture is extracted with EtOAc (10 ml×3). The combined organic phase is washed with water, and treated with concentrated HCl (1.0 ml). The mixture is stirred at rt for 2 hr, and then basified with saturated sodium carbonate solution. The organic phase is collected, and the aqueous phase is extracted with EtOAc (10 ml×2). The combined organic phase is dried over sodium sulfate, and concentrated. The residue is purified by PTLC (EtOAc/4% TEA) to give the title compound. 1H NMR (300 MHz, CDCl3) δ 7.74 (1H, s), 7.59 (1H, dd), 7.41 (1H, dd), 7.10˜7.25 (3H, m), 6.72 (1H, d), 5.22 (1H, s), 3.81 (1H, m), 3.04˜3.52 (7H, m), 2.78˜2.98 (2H, m), 2.67 (1H, m), 2.55 (3H, s), 2.41 (1H, m), 2.27 (1H, m), 1.96˜2.14 (4H), 1.60˜1.92 (4H); MS (+VE) m/z 466.00 (M+).

Workup

  1. customto quench
  2. customthe reaction
  3. extractionthe mixture is extracted with EtOAc (10 ml×3)
  4. washThe combined organic phase is washed with water
  5. additiontreated with concentrated HCl (1.0 ml)
  6. stirringThe mixture is stirred at rt for 2 hr
  7. customThe organic phase is collected
  8. extractionthe aqueous phase is extracted with EtOAc (10 ml×2)
  9. dry with materialThe combined organic phase is dried over sodium sulfate
  10. concentrationconcentrated
  11. customThe residue is purified by PTLC (EtOAc/4% TEA)

Sources & evidence

ORD record
ord-9d2bb7ef7c114ac39f7e6cbc1bb18847
Source dataset
uspto-grants-2010_09
Patent number
US07795262B2

Reaction notes

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