Sodium Bicarbonate → 4-[4-(3-Indolyl)piperidinomethyl]-2-propionylaminothiazole

HRID 1252070Notes

Reaction equation

HRID 1252070 reaction equation
[C:1]([NH:5][C:6]1[S:7][CH:8]=[C:9]([CH2:11]Cl)[N:10]=1)(=[O:4])[CH2:2][CH3:3].[NH:13]1[CH2:18][CH2:17][CH:16]([C:19]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[NH:21][CH:20]=2)[CH2:15][CH2:14]1.C(=O)([O-])O.[Na+]>CN(C)C=O>[NH:21]1[C:22]2[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:19]([CH:16]2[CH2:17][CH2:18][N:13]([CH2:11][C:9]3[N:10]=[C:6]([NH:5][C:1](=[O:4])[CH2:2][CH3:3])[S:7][CH:8]=3)[CH2:14][CH2:15]2)=[CH:20]1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 7022353-(4-Piperidinyl)-1H-indoleHCID 103980162-Propionylamino-4-chloromethylthiazole

Product 1

HCID 103169664-[4-(3-Indolyl)piperidinomethyl]-2-propionylaminothiazoleYield 70.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-propionylamino-4-chloromethylthiazol (5.11 g), 3-(4-piperidyl)indole (5 g), sodium hydrogen carbonate (2.31 g) and N,N-dimethylformamide (25 ml) was heated at 102° to 103° C. with bubbling nitrogen gas and stirring for 6 hours. The reaction mixture was filtered and the filtrate was concentrated. The residue was subjected to column chromatography on silica gel and the column was eluted with a mixture of chloroform and methanol (10:1 V/V). The fractions containing the desired compound were combined and concentrated and ethanol was added thereto. The solution was concentrated again and the residue was triturated with diisopropyl ether to give 4-[4-(3-indolyl)piperidinomethyl]-2-propionylaminothiazole (6.50 g).

Workup

  1. temperaturewas heated at 102° to 103° C. with bubbling nitrogen gas
  2. filtrationThe reaction mixture was filtered
  3. concentrationthe filtrate was concentrated
  4. washthe column was eluted with a mixture of chloroform and methanol (10:1 V/V)
  5. additionThe fractions containing the desired compound
  6. concentrationconcentrated
  7. additionethanol was added
  8. concentrationThe solution was concentrated again
  9. customthe residue was triturated with diisopropyl ether

Sources & evidence

ORD record
ord-ad75e563d6894b61ac6a4462bb8cd872
Source dataset
uspto-grants-1988_05
Patent number
US04742057

Reaction notes

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