Ethyl 3-methyl-1-phenylpyrazole-5-carboxylate → HCID 20497960, compound

HRID 2166818Notes

Reaction equation

HRID 2166818 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[N:29]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[N:28]=[C:27]([CH3:36])[CH:26]=1)=O)C>ClCCl>[CH3:36][C:27]1[CH: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])[N:29]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[N:28]=1

Participants

5

Reactant 3

HCID 2746772Ethyl 3-methyl-1-phenylpyrazole-5-carboxylateHCID 30386693-(2,3,5,6-Tetrahydroimidazo[2,1-b][1,3]thiazol-6-yl)anilineHCID 16682925Trimethylaluminum

Product 1

HCID 20497960HCID 20497960, compoundYield 73.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To 6-(m-aminophenyl)-2,3,5,6-tetrahydroimidazo[2,1-b]thiazole (1.43 g; 6.5 mmol) in dry dichloromethane (30 ml) under nitrogen at room temperature was added trimethylaluminium (10 ml; 25% in hexane). After 30 mins 3-methyl-1-phenylpyrazole 5-carboxylic acid ethyl ester (1.5 g, 6.5 mmol) in dry dichloromethane (5 ml) was added and the mixture heated under reflux for 24 hr. The reaction was quenched by the slow addition of hydrochloric acid (20 ml; 2 N aqueous), the resulting two phase system basified with aqueous ammonia solution (5 N) and extracted with chloroform (3×200 ml). After drying (MgSO4) the combined organic phases were concentrated in vacuo to afford an oil which was separated by column chromatography on alumina eluting with chloroform. The major band was further purified by column chromatography on silica gel (60-120 mesh) eluting with chloroform to afford the amide (1.93 g; 62%) which was converted into its hydrochloride salt by the addition of isopropanolic hydrogen chloride. Recrystallisation from ethanol afforded the pure salt (0.7 g).

Workup

  1. temperaturethe mixture heated
  2. temperatureunder reflux for 24 hr
  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. dry with materialAfter drying (MgSO4) the combined organic phases
  6. concentrationwere concentrated in vacuo
  7. customto afford an oil which
  8. customwas separated by column chromatography on alumina eluting with chloroform
  9. customThe major band was further purified by column chromatography on silica gel (60-120 mesh)
  10. washeluting with chloroform

Sources & evidence

ORD record
ord-8ab6246b7b32419d8b7d58c5dbad6e7a
Source dataset
uspto-grants-1983_06
Patent number
US04389406

Reaction notes

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