2-Acetamido-4-chloromethylthiazole → N-(4-((4-(1H-Indol-3-yl)piperidin-1-yl)methyl)thiazol-2-yl)acetamide

HRID 1252066Notes

Reaction equation

HRID 1252066 reaction equation
[C:1]([NH:4][C:5]1[S:6][CH:7]=[C:8]([CH2:10]Cl)[N:9]=1)(=[O:3])[CH3:2].[NH:12]1[CH2:17][CH2:16][CH:15]([C:18]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[NH:20][CH:19]=2)[CH2:14][CH2:13]1.C(=O)([O-])O.[Na+]>CN(C)C=O.O1CCCC1>[C:1]([NH:4][C:5]1[S:6][CH:7]=[C:8]([CH2:10][N:12]2[CH2:17][CH2:16][CH:15]([C:18]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[NH:20][CH:19]=3)[CH2:14][CH2:13]2)[N:9]=1)(=[O:3])[CH3:2]

Participants

6

Reactant 3

HCID 819632-Acetamido-4-chloromethylthiazoleHCID 516892Sodium BicarbonateHCID 7022353-(4-Piperidinyl)-1H-indole

Product 1

HCID 14129784N-(4-((4-(1H-Indol-3-yl)piperidin-1-yl)methyl)thiazol-2-yl)acetamideYield 30.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

2-Acetylamino-4-chloromethylthiazole (480 mg), 3-(4-piperidyl)indole (500 mg) and sodium hydrogen carbonate (310 mg) was refluxed in a mixture of N,N-dimethylformamide (5 ml) and tetrahydrofuran (7 ml) for 1 hour and 40 minutes. After the reaction mixture cooled to ambient temperature, it was concentrated under reduced pressure. After addition of water (50 ml), the residue was extracted with ethyl acetate (50 ml) twice. The extract was washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to column chromatography on silica gel and elution was carried out with a mixture of chloroform and methanol (30:1 V/V). The eluate gave 2-acetylamino-4-[4-(3-indolyl)piperidinomethyl]thiazole (270 mg).

Workup

  1. concentrationit was concentrated under reduced pressure
  2. additionAfter addition of water (50 ml)
  3. extractionthe residue was extracted with ethyl acetate (50 ml) twice
  4. washThe extract was washed with a saturated aqueous solution of sodium chloride
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. washThe residue was subjected to column chromatography on silica gel and elution
  8. additionwas carried out with a mixture of chloroform and methanol (30:1 V/V)

Sources & evidence

ORD record
ord-2dbb26433cc1471a9e3144d3867d65c5
Source dataset
uspto-grants-1988_05
Patent number
US04742057

Reaction notes

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