Ethylenediamine → 4-(5-(4-(3-(4,5-Dihydro-1H-imidazol-2-yl)propyl)phenyl)-8-oxo-6-thioxo-5,7-diaza-spiro[3.4]octan-7-yl)-2-(trifluoromethyl)benzonitrile

HRID 1192880Notes

Reaction equation

HRID 1192880 reaction equation
[O:1]=[C:2]1[C:6]2([CH2:9][CH2:8][CH2:7]2)[N:5]([C:10]2[CH:15]=[CH:14][C:13]([CH2:16][CH2:17][CH2:18][CH:19]=O)=[CH:12][CH:11]=2)[C:4](=[S:21])[N:3]1[C:22]1[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[C:24]([C:30]([F:33])([F:32])[F:31])[CH:23]=1.[CH2:34]([NH2:37])[CH2:35][NH2:36].BrN1C(=O)CCC1=O>ClCCl>[NH:36]1[CH2:35][CH2:34][N:37]=[C:19]1[CH2:18][CH2:17][CH2:16][C:13]1[CH:12]=[CH:11][C:10]([N:5]2[C:4](=[S:21])[N:3]([C:22]3[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[C:24]([C:30]([F:33])([F:32])[F:31])[CH:23]=3)[C:2](=[O:1])[C:6]32[CH2:7][CH2:8][CH2:9]3)=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 67184N-bromobutanimideHCID 252681274-(8-Oxo-5-(4-(4-oxobutyl)phenyl)-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)-2-(trifluoromethyl)benzonitrile

Product 1

HCID 866300094-(5-(4-(3-(4,5-Dihydro-1H-imidazol-2-yl)propyl)phenyl)-8-oxo-6-thioxo-5,7-diaza-spiro[3.4]octan-7-yl)-2-(trifluoromethyl)benzonitrileYield 39.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

The mixture of 4-(8-Oxo-5-(4-(4-oxobutyl)phenyl)-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)-2-(trifluoromethyl)benzonitrile (68) [ND-10] (15 mg, 0.03 mmol) and ethylene diamine (2 μL, 0.04 mmol) in dry dichloromethane (3 mL) was stirred at 0° C. for 30 min under argon. N-Bromosuccinimide (NBS, 6 mg, 0.04 mmol) was added to the mixture and the resulting solution was stirred overnight at 21° C. Reaction was quenched by the addition of saturated NaHCO3 solution. The mixture was extracted with dichloromethane. The organic layer was dried over MgSO4, and evaporated in vacuo. The residue was purified by flash column chromatography (ethanol:ethyl acetate, 1:4) to give 4-(5-(4-(3-(4,5-Dihydro-1H-imidazol-2-yl)propyl)phenyl)-8-oxo-6-thioxo-5,7-diaza-spiro[3.4]octan-7-yl)-2-(trifluoromethyl)benzonitrile (65) [ND-11] (6 mg, 35%): 1H NMR δ 7.98 (d, 1H, J=1.9 Hz) 7.97 (d, 1H, J=8.3 Hz) 7.85 (dd, 1H, J=8.3, 1.9 Hz), 7.46 (d, 1H, J=8.2 Hz) 7.25 (d, 1H, J=8.2 Hz), 4.72 (br s, 1H), 3.67-3.80 (m, 4H), 2.85-3.05 (m, 2H), 2.57-2.70 (m, 2H), 2.43-2.57 (m, 4H), 2.15-2.30 (m, 1H), 1.63-1.80 (m, 3H).

Workup

  1. stirringthe resulting solution was stirred overnight at 21° C
  2. customReaction
  3. customwas quenched by the addition of saturated NaHCO3 solution
  4. extractionThe mixture was extracted with dichloromethane
  5. dry with materialThe organic layer was dried over MgSO4
  6. customevaporated in vacuo
  7. customThe residue was purified by flash column chromatography (ethanol:ethyl acetate, 1:4)

Sources & evidence

ORD record
ord-aec54857a44e4ed9ba2eb97667a17e42
Source dataset
uspto-grants-2014_03
Patent number
US08680291B2

Reaction notes

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