Sodium Iodide → 2-[6-bromo-1-(2-chloro-phenyl)-3,4-dihydro-1H-isoquinolin-2-yl]-1-(4-cyclobutyl-piperazin-1-yl)-ethanone

HRID 1713086Notes

Reaction equation

HRID 1713086 reaction equation
Cl.[Br:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[Cl:19])[NH:8][CH2:7][CH2:6]2.Cl[CH:21]1[CH2:26][N:25]([CH:27]2[CH2:30][CH2:29][CH2:28]2)[CH2:24][CH2:23][NH:22]1.[C:31](N)(=[O:33])[CH3:32].C([O-])([O-])=O.[K+].[K+].[Na+].[I-]>C(#N)C.O>[Br:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[Cl:19])[N:8]([CH2:32][C:31]([N:22]1[CH2:23][CH2:24][N:25]([CH:27]3[CH2:30][CH2:29][CH2:28]3)[CH2:26][CH2:21]1)=[O:33])[CH2:7][CH2:6]2

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 668777716-bromo-1-(2-chloro-phenyl)-1,2,3,4-tetrahydroisoquinoline HCl saltHCID 668779022-Chloro-(4-cyclobutyl-piperazine) acetamide

Product 1

HCID 247512302-[6-bromo-1-(2-chloro-phenyl)-3,4-dihydro-1H-isoquinolin-2-yl]-1-(4-cyclobutyl-piperazin-1-yl)-ethanone

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a stirred suspension of 6-bromo-1-(2-chloro-phenyl)-1,2,3,4-tetrahydroisoquinoline HCl salt (400 mg, 1.11 mmol) in acetonitrile (10.0 ml) is added 2-chloro-(4-cyclobutyl-piperazine)-acetamide (241 mg, 1.11 mmol, 1.0 eq.), K2CO3 (306 mg, 2.22 mmol, 2.0 eq.), and NaI (50 mg). The resulting mixture is stirred at rt overnight. Water (10.0 ml) is added to quench the reaction, and the acetonitrile is evaporated. The residue is extracted with DCM (10 ml×3), and the combined extracts are dried over sodium sulfate. The solvent is removed under reduced pressure, and the residue is purified through PTLC (EtOAc/4% TEA) to give the title compound. 1H NMR (300 MHz, CDCl3) δ 7.40 (1H, dd), 7.18˜7.32 (5H, m), 6.49 (1H, d), 5.10 (1H, s), 3.81 (1H, m), 3.46 (1H, m), 3.04˜3.40 (6H, m), 2.60˜2.88 (3H, m), 2.41 (1H, m), 2.27 (1H, m), 1.96˜2.14 (4H), 1.60˜1.92 (4H); MS (+VE) m/z 503.9 (M++1).

Workup

  1. customto quench
  2. customthe reaction
  3. customthe acetonitrile is evaporated
  4. extractionThe residue is extracted with DCM (10 ml×3)
  5. dry with materialthe combined extracts are dried over sodium sulfate
  6. customThe solvent is removed under reduced pressure
  7. customthe residue is purified through PTLC (EtOAc/4% TEA)

Sources & evidence

ORD record
ord-05d2797dc9ad4a6d8fcac32e3e3a5c32
Source dataset
uspto-grants-2010_09
Patent number
US07795262B2

Reaction notes

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