Sodium Iodide → 6-(Benzyloxy)-2-[2-(4-cyclobutylpiperazin-1-yl)-2-oxoethyl]-1,2,3,4-tetrahydroisoquinoline

HRID 1713079Notes

Reaction equation

HRID 1713079 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[CH2:15][NH:14][CH2:13][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[CH:20]1[CH2:25][N:24]([CH:26]2[CH2:29][CH2:28][CH2:27]2)[CH2:23][CH2:22][NH:21]1.[C:30](N)(=[O:32])[CH3:31].C([O-])([O-])=O.[K+].[K+].[Na+].[I-]>C(#N)C.O>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[CH2:15][N:14]([CH2:31][C:30]([N:21]1[CH2:22][CH2:23][N:24]([CH:26]3[CH2:29][CH2:28][CH2:27]3)[CH2:25][CH2:20]1)=[O:32])[CH2:13][CH2:12]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 106100436-(Benzyloxy)-1,2,3,4-tetrahydroisoquinolineHCID 668779022-Chloro-(4-cyclobutyl-piperazine) acetamide

Product 1

HCID 574205646-(Benzyloxy)-2-[2-(4-cyclobutylpiperazin-1-yl)-2-oxoethyl]-1,2,3,4-tetrahydroisoquinoline

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of 6-benzyloxy-1,2,3,4-tetrahydroisoquinoline (1.5 g, 6.26 mmol) in acetonitrile (20.0 ml) is added 2-chloro-(4-cyclobutyl-piperazine)-acetamide (1.36 g, 6.26 mmol, 1.0 eq.), K2CO3 (1.73 g, 12.5 mmol, 2.0 eq.), and NaI (180 mg). The resulting mixture is stirred at rt overnight. Water (20.0 ml) is added to quench the reaction, and then the acetonitrile is evaporated. The residue is extracted with DCM (20 ml×3). The combined organic phase is dried over sodium sulfate, and the solvent is removed under reduced pressure to give a residue that is purified by PTLC (EtOAc/4% TEA) to give the title compound. 1H NMR (300 MHz, CDCl3) δ 7.30-7.44 (5H, m), 6.84-6.94 (1H, m), 6.70-6.80 (2H, 1 m), 5.20 (2H, s), 3.60-3.74 (6H, m), 3.56 (2H, s), 2.62-2.92 (5H, m), 2.22-2.32 (4H, m), 1.60˜2.10 (6H, m); MS (+VE) m/z 420.2 (M++1).

Workup

  1. customto quench
  2. customthe reaction
  3. customthe acetonitrile is evaporated
  4. extractionThe residue is extracted with DCM (20 ml×3)
  5. dry with materialThe combined organic phase is dried over sodium sulfate
  6. customthe solvent is removed under reduced pressure
  7. customto give a residue that
  8. customis purified by PTLC (EtOAc/4% TEA)

Sources & evidence

ORD record
ord-5851f3d8a14a448b84a0ca5c825ece0a
Source dataset
uspto-grants-2010_09
Patent number
US07795262B2

Reaction notes

Loading…