Sodium Iodide → 2-[2-(4-Cyclobutyl-piperazin-1-yl)-2-oxo-ethyl]-1,2,3,4-tetrahydro-isoquinoline-6-carboxylic acid ethyl ester

HRID 1713103Notes

Reaction equation

HRID 1713103 reaction equation
Cl.[CH2:2]([O:4][C:5]([C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[CH2:13][NH:12][CH2:11][CH2:10]2)=[O:6])[CH3:3].Cl[CH:18]1[CH2:23][N:22]([CH:24]2[CH2:27][CH2:26][CH2:25]2)[CH2:21][CH2:20][NH:19]1.[C:28](N)(=[O:30])[CH3:29].C([O-])([O-])=O.[K+].[K+].[Na+].[I-]>C(#N)C.O>[CH2:2]([O:4][C:5]([C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[CH2:13][N:12]([CH2:29][C:28]([N:19]1[CH2:20][CH2:21][N:22]([CH:24]3[CH2:27][CH2:26][CH2:25]3)[CH2:23][CH2:18]1)=[O:30])[CH2:11][CH2:10]2)=[O:6])[CH3:3]

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 668779022-Chloro-(4-cyclobutyl-piperazine) acetamideHCID 66878486Ethyl 1,2,3,4-tetrahydroisoquinoline-6-carboxylate hydrochloride

Product 1

HCID 574206152-[2-(4-Cyclobutyl-piperazin-1-yl)-2-oxo-ethyl]-1,2,3,4-tetrahydro-isoquinoline-6-carboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
40 °C

Procedure

To a stirred solution of 1,2,3,4-tetrahydro-isoquinoline-6-carboxylic acid ethyl ester hydrochloride (530 mg, 2.20 mmol) in acetonitrile (20.0 ml) are added 2-chloro-(4-cyclobutyl-piperazine)-acetamide (474 mg, 2.20 mmol, 1.0 eq.), K2CO3 (608 mg, 4.40 mmol, 2.0 eq.) and NaI (100 mg). The resulting mixture is stirred at 40° C. overnight. Water (10.0 ml) is added to quench the reaction, and the acetonitrile is evaporated. The residue is extracted with DCM (20 ml×3), and the combined organic phase is dried over sodium sulfate and concentrated. The residue is purified by silica gel flash chromatography (EtOAc/4% TEA) to give the title compound. 386.1 (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. concentrationconcentrated
  7. customThe residue is purified by silica gel flash chromatography (EtOAc/4% TEA)

Sources & evidence

ORD record
ord-099187d521054ba0af466a15eb43fc04
Source dataset
uspto-grants-2010_09
Patent number
US07795262B2

Reaction notes

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