Sodium Iodide → 1-(4-{2-[2-(4-Cyclobutylpiperazin-1-yl)-2-oxoethyl]-1,2,3,4-tetrahydroisoquinolin-6-yl}phenyl)ethanone

HRID 1713093Notes

Reaction equation

HRID 1713093 reaction equation
[CH2:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]3[CH:16]=[CH:15][C:14]([C:17](=[O:19])[CH3:18])=[CH:13][CH:12]=3)=[CH:8][CH:9]=2)[CH2:4][CH2:3][NH:2]1.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>[C:17]([C:14]1[CH:15]=[CH:16][C:11]([C:7]2[CH:6]=[C:5]3[C:10](=[CH:9][CH:8]=2)[CH2:1][N:2]([CH2:32][C:31]([N:22]2[CH2:23][CH2:24][N:25]([CH:27]4[CH2:30][CH2:29][CH2:28]4)[CH2:26][CH2:21]2)=[O:33])[CH2:3][CH2:4]3)=[CH:12][CH:13]=1)(=[O:19])[CH3:18]

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 574205691-(4-(1,2,3,4-Tetrahydroisoquinolin-6-yl)phenyl)ethan-1-oneHCID 668779022-Chloro-(4-cyclobutyl-piperazine) acetamide

Product 1

HCID 247513731-(4-{2-[2-(4-Cyclobutylpiperazin-1-yl)-2-oxoethyl]-1,2,3,4-tetrahydroisoquinolin-6-yl}phenyl)ethanone

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred solution of 1-[4-(1,2,3,4-tetrahydro-isoquinolin-6-yl)-phenyl]-ethanone (216 mg, 0.86 mmol) in acetonitrile (5.0 ml) is added 2-chloro-(4-cyclobutyl-piperazine)-acetamide (186 mg, 0.86 mmol, 1.0 eq.), K2CO3 (238 mg, 1.72 mmol, 2.0 eq.) and NaI (50 mg). The resulting mixture is stirred at 50° C. 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). 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 8.01 (2H, d), 7.66 (2H, d), 7.36˜7.44 (2H, m), 7.12 (1H, d), 3.74 (2H, s), 3.60˜3.70 (4H, m), 3.38 (2H, s), 2.97 (2H, t), 2.83 (2H, t), 2.66 (1H, m), 2.64 (3H, s), 2.29 (4H, m), 1.60˜2.08 (6H); MS (+VE) m/z 432.2 (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 combined organic phase is dried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue is purified by PTLC (EtOAc/4% TEA)

Sources & evidence

ORD record
ord-9e7c6f96612b419c85d9734e24f4aba3
Source dataset
uspto-grants-2010_09
Patent number
US07795262B2

Reaction notes

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