Sodium Iodide → (S)-2-(4-((2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)(propyl)amino)butyl)isoindoline-1,3-dione

HRID 2061627Notes

Reaction equation

HRID 2061627 reaction equation
Br[CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[C:10](=[O:11])[C:9]2=[CH:12][CH:13]=[CH:14][CH:15]=[C:8]2[C:7]1=[O:16].C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[Na+].[CH3:25][CH2:26][CH2:27][NH:28][C@@H:29]1[CH2:38][C:33]2[S:34][C:35]([NH2:37])=[N:36][C:32]=2[CH2:31][CH2:30]1>C(#N)C>[NH2:37][C:35]1[S:34][C:33]2[CH2:38][C@@H:29]([N:28]([CH2:27][CH2:26][CH3:25])[CH2:2][CH2:3][CH2:4][CH2:5][N:6]3[C:10](=[O:11])[C:9]4[C:8](=[CH:15][CH:14]=[CH:13][CH:12]=4)[C:7]3=[O:16])[CH2:30][CH2:31][C:32]=2[N:36]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 93575N-(4-Bromobutyl)phthalimideHCID 119570Pramipexole

Product 1

HCID 58369715(S)-2-(4-((2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)(propyl)amino)butyl)isoindoline-1,3-dioneYield 90.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

N-(4-bromobutyl)-phthalimide (2.25 g, 7.98 mmol), cesium carbonate (2.6 g, 7.98 mmol), and sodium iodide (1.80 g, 12 mmol) were added to a solution of pramipexole 1 (1.53 g, 7.25 mmol) in acetonitrile (50 mL). After refluxing for 3 hours, the mixture was evaporated in vacuo. The residue was partitioned between ethyl acetate and water. The organic layer was separated and washed with brine, and dried over anhydrous Na2SO4. Flash column chromatography (MeOH/EtOAc, 5:95) gave 13 as a colorless oil (2.7 g, 90.4%). 1H NMR (CDCl3, 300 MHz) δ 7.88-8.00 (m, 2H), 7.78-7.60 (m, 2H), 4.90 (s, 2H), 3.70 (t, J=7.2 Hz, 2H), 3.10-2.95 (m, 1H), 2.78-2.30 (m, 8H), 2.05-1.90 (m, 1H), 1.77-1.60 (m, 3H), 1.56-1.40 (m, 4H), 0.87 (t, J=7.2 Hz, 3H); 13C NMR (CDCl3, 75 MHz) δ168.89, 165.83, 145.53, 134.28, 132.53, 123.58, 117.96, 57.59, 52.97, 50.41, 38.34, 27.01, 26.81, 26.71, 26.05, 25.33, 22.64, 12.24.

Workup

  1. temperatureAfter refluxing for 3 hours
  2. customthe mixture was evaporated in vacuo
  3. customThe residue was partitioned between ethyl acetate and water
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried over anhydrous Na2SO4

Sources & evidence

ORD record
ord-9e5071c65577407b880d653653ca8104
Source dataset
uspto-grants-2012_10
Patent number
US08283368B2

Reaction notes

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