Sodium Iodide → 1-(4-cyclobutyl-piperazin-1-yl)-2-(6-methoxy-3,4-dihydro-1H-isoquinolin-2-yl)-ethanone

HRID 1713078Notes

Reaction equation

HRID 1713078 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH2:9][NH:8][CH2:7][CH2:6]2.Cl[CH:14]1[CH2:19][N:18]([CH:20]2[CH2:23][CH2:22][CH2:21]2)[CH2:17][CH2:16][NH:15]1.[C:24](N)(=[O:26])[CH3:25].C([O-])([O-])=O.[K+].[K+].[Na+].[I-]>C(#N)C.O>[CH:20]1([N:18]2[CH2:17][CH2:16][N:15]([C:24](=[O:26])[CH2:25][N:8]3[CH2:7][CH2:6][C:5]4[C:10](=[CH:11][CH:12]=[C:3]([O:2][CH3:1])[CH:4]=4)[CH2:9]3)[CH2:14][CH2:19]2)[CH2:23][CH2:22][CH2:21]1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 393566-Methoxy-1,2,3,4-tetrahydroisoquinolineHCID 668779022-Chloro-(4-cyclobutyl-piperazine) acetamide

Product 1

HCID 247512261-(4-cyclobutyl-piperazin-1-yl)-2-(6-methoxy-3,4-dihydro-1H-isoquinolin-2-yl)-ethanone

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of 6-methoxy-1,2,3,4-tetrahydroisoquinoline (163 mg, 1.0 mmol) in acetonitrile (5.0 ml) is added 2-chloro-(4-cyclobutyl-piperazine)-acetamide (216 mg, 1.0 mmol, 1.0 eq.), K2CO3 (376 mg, 2.0 mmol, 2.0 eq.), and NaI (30 mg). The resulting mixture is stirred at rt overnight. Water (10.0 ml) is added to quench the reaction, and then the acetonitrile is evaporated. The residue is extracted with DCM (10 ml×3). The extracts are dried over sodium sulfate, and the solvent is removed under reduced pressure to yield a residue that is purified through PTLC (EtOAc/4% TEA) to give the title compound. 1H NMR (300 MHz, CDCl3) δ 6.92 (1H, d), 6.70 (1H, dd), 6.63 (1H, d), 3.77 (3H, s), 3.58˜3.68 (6H, m), 3.33 (2H, s), 2.86 (2H, t), 2.74 (2H, t), 2.65 (1H, m), 2.27 (4H, m), 1.62˜2.06 (6H, m); MS (+VE) m/z 344.2 (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 extracts are dried over sodium sulfate
  6. customthe solvent is removed under reduced pressure
  7. customto yield a residue that
  8. customis purified through PTLC (EtOAc/4% TEA)

Sources & evidence

ORD record
ord-3670cd2a4f1f4a39bd2af8de7783d979
Source dataset
uspto-grants-2010_09
Patent number
US07795262B2

Reaction notes

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