Sodium Iodide → Brexpiprazole

HRID 1364263Notes

Reaction equation

HRID 1364263 reaction equation
Cl[CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:16]=[C:15]2[C:10]([CH:11]=[CH:12][C:13](=[O:17])[NH:14]2)=[CH:9][CH:8]=1.Cl.[S:19]1[CH:23]=[CH:22][C:21]2[C:24]([N:28]3[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]3)=[CH:25][CH:26]=[CH:27][C:20]1=2.C(=O)([O-])[O-].[K+].[K+].[I-].[Na+]>O.CN(C)C=O>[S:19]1[CH:23]=[CH:22][C:21]2[C:24]([N:28]3[CH2:33][CH2:32][N:31]([CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]4[CH:16]=[C:15]5[C:10]([CH:11]=[CH:12][C:13](=[O:17])[NH:14]5)=[CH:9][CH:8]=4)[CH2:30][CH2:29]3)=[CH:25][CH:26]=[CH:27][C:20]1=2

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 566050407-(4-Chlorobutoxy)-1H-quinolin-2-oneHCID 574825411-(1-Benzothiophen-4-yl)piperazine hydrochloride

Product 1

HCID 11978813Brexpiprazole

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 9.0 g of 7-(4-chlorobutoxy)-1H-quinolin-2-one, 10 g of 1-benzo[b]thiophene-4-yl-piperazine hydrochloride, 14 g of potassium carbonate, 6 g of sodium iodide and 90 ml of dimethylformamide was stirred for 2 hours at 80° C. Water was added to the reaction solution and precipitated crystals were separated by filtration. The crystals were dissolved in a mixed solvent of dichloromethane and methanol, dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane:methanol=100:3). Recrystallized from ethanol, 13.6 g of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy-]-1H-quinolin-2-one in the form of a white powder was obtained.

Workup

  1. customprecipitated crystals
  2. customwere separated by filtration
  3. dissolutionThe crystals were dissolved in a mixed solvent of dichloromethane and methanol
  4. dry with materialdried over magnesium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (dichloromethane:methanol=100:3)
  7. customRecrystallized from ethanol, 13.6 g of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy-]-1H-quinolin-2-one in the form of a white powder
  8. customwas obtained

Sources & evidence

ORD record
ord-14688980d6e949338dcfa049d55e4695
Source dataset
uspto-grants-2011_02
Patent number
US07888362B2

Reaction notes

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