Ammonium Chloride → 2-Ethoxy-5-(4-ethyl-1-piperazinylsulfonyl)benzamidine

HRID 892228Notes

Reaction equation

HRID 892228 reaction equation
C[Al](C)C.[Cl-].[NH4+:6].[CH2:7]([O:9][C:10]1[CH:17]=[CH:16][C:15]([S:18]([N:21]2[CH2:26][CH2:25][N:24]([CH2:27][CH3:28])[CH2:23][CH2:22]2)(=[O:20])=[O:19])=[CH:14][C:11]=1[C:12]#[N:13])[CH3:8]>C1(C)C=CC=CC=1>[CH2:7]([O:9][C:10]1[CH:17]=[CH:16][C:15]([S:18]([N:21]2[CH2:22][CH2:23][N:24]([CH2:27][CH3:28])[CH2:25][CH2:26]2)(=[O:20])=[O:19])=[CH:14][C:11]=1[C:12]([NH2:6])=[NH:13])[CH3:8]

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 99670112-Ethoxy-5-(4-ethyl-1-piperazinylsulfonyl)benzonitrileHCID 16682925Trimethylaluminum

Product 1

HCID 101320622-Ethoxy-5-(4-ethyl-1-piperazinylsulfonyl)benzamidineYield 28.6%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Trimethylaluminium (10 mL, 2 Molar solution in hexanes) was added dropwise to a slurry of ammonium chloride (1.07 g, 0.02 Mol) in toluene (15 mL) at 0° C. The mixture was stirred without cooling until gas evolution stopped. 2-ethoxy-5-(4-ethyl-1-piperazinylsulfonyl)benzonitrile (the compound of Preparation 7) (3.23 g, 0.01 Mol) was then added and was washed in with toluene (5 mL) before the reaction was stirred at 80° C. for 40 h. After cooling to room temperature silica gel (15 g) and dichloromethane (100 mL) were added. The mixture was then filtered and the solids were washed with dichloromethane/methanol mixtures. The combined filtrate and washings were evaporated and the residue was chromatographed over silica gel using dichloromethane methanol mixtures to afford 1.08 g, 28.6% of the title compound. M/Z=found 341 (M+H). 1H NMR (CD3OD) 1.28 (t, 3H) 1.49 (t, 3H) 2.97 (q, 2H) 3.14 (br, s, 4H) 3.33(br, s, 4H) 4.32 (q, 2H) 7.45(d, 1H) 7.96 (d, 1H) 8.05 (dd, 1H).

Workup

  1. temperaturewithout cooling until gas evolution
  2. additionwas then added
  3. washwas washed in with toluene (5 mL) before the reaction
  4. stirringwas stirred at 80° C. for 40 h
  5. additionwere added
  6. filtrationThe mixture was then filtered
  7. washthe solids were washed with dichloromethane/methanol mixtures
  8. customThe combined filtrate and washings were evaporated
  9. customthe residue was chromatographed over silica gel

Sources & evidence

ORD record
ord-db93252b1b924224aaad45dcf5e45f61
Source dataset
uspto-grants-2006_02
Patent number
US07005520B2

Reaction notes

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