3-Aminolevamisole → 6-[m-(5-Methyl-1-phenylpyrazole-3-carboxamido)phenyl]-2,3,5,6-tetrahydroimidazo[2,1-b]thiazole

HRID 2166819Notes

Reaction equation

HRID 2166819 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:8]2[CH2:15][N:14]3[C:10]([S:11][CH2:12][CH2:13]3)=[N:9]2)[CH:5]=[CH:6][CH:7]=1.C[Al](C)C.C([O:22][C:23]([C:25]1[CH:29]=[C:28]([CH3:30])[N:27]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[N:26]=1)=O)C>ClCCl>[CH3:30][C:28]1[N:27]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[N:26]=[C:25]([C:23]([NH:1][C:2]2[CH:3]=[C:4]([CH:8]3[CH2:15][N:14]4[C:10]([S:11][CH2:12][CH2:13]4)=[N:9]3)[CH:5]=[CH:6][CH:7]=2)=[O:22])[CH:29]=1

Participants

5

Reactant 3

HCID 30386693-AminolevamisoleHCID 10900438Ethyl 5-methyl-1-phenyl-1H-pyrazole-3-carboxylateHCID 16682925Trimethylaluminum

Product 1

HCID 204979616-[m-(5-Methyl-1-phenylpyrazole-3-carboxamido)phenyl]-2,3,5,6-tetrahydroimidazo[2,1-b]thiazoleYield 69%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To 6-(m-aminophenyl)-2,3,5,6-tetrahydroimidazo[2,1-b]thiazole (1.9 g, 8.7 mmol) in dry dichloromethane (40 ml) under nitrogen at room temperature was added trimethylaluminium (6 ml: 25% in hexane). After 20 min 5-methyl-1-phenylpyrazole 3-carboxylic acid ethyl ester (2 g, 8.7 mmol) in dry dichloromethane (5 ml) was added and the mixture heated under reflux for 3 days. The reaction was quenched by the slow addition of hydrochloric acid (20 ml, 2 N aqueous), basified with aqueous ammonia solution (5 N) and extracted with chloroform (3×200 ml). After drying the organic phase was concentrated in vacuo to afford an oil which was separated by column chromatography on alumina eluting with chloroform to afford the amide (2.41 g; 69%). Addition of isopropanolic hydrogen chloride gave the hydrochloride salt (1.56 g) recrystallised from ethanol.

Workup

  1. temperaturethe mixture heated
  2. temperatureunder reflux for 3 days
  3. customThe reaction was quenched by the slow addition of hydrochloric acid (20 ml, 2 N aqueous)
  4. extractionextracted with chloroform (3×200 ml)
  5. customAfter drying the organic phase
  6. concentrationwas concentrated in vacuo
  7. customto afford an oil which
  8. customwas separated by column chromatography on alumina eluting with chloroform

Sources & evidence

ORD record
ord-734027a5a4bd4fe0bc67026a03d15e8a
Source dataset
uspto-grants-1983_06
Patent number
US04389406

Reaction notes

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