Benzene → 4-[3-[[[[3-(4-Cyclohexyl-1-piperazinyl)propyl]amino]-carbonothioyl]amino]phenyl]-1,4-dihydro-2,6-dimethyl-3,5-pyrazinedicarboxylic acid, dimethyl ester

HRID 566907Notes

Reaction equation

HRID 566907 reaction equation
[CH3:1][C:2]1[NH:3][C:4]([CH3:25])=[C:5]([C:21]([O:23][CH3:24])=[O:22])[N:6]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([N:18]=[C:19]=[S:20])[CH:13]=2)[C:7]=1[C:8]([O:10][CH3:11])=[O:9].[CH:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>>[CH:26]1([N:3]2[CH2:2][CH2:7][N:6]([CH2:12][CH2:13][CH2:14][NH:18][C:19]([NH:18][C:14]3[CH:13]=[C:12]([N:6]4[C:7]([C:8]([O:10][CH3:11])=[O:9])=[C:2]([CH3:1])[NH:3][C:4]([CH3:25])=[C:5]4[C:21]([O:23][CH3:24])=[O:22])[CH:17]=[CH:16][CH:15]=3)=[S:20])[CH2:5][CH2:4]2)[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1

Participants

3

Reactant 2

HCID 241BenzeneHCID 155242381,4-Dihydro-2,6-dimethyl-4-(3-isothiocyanatophenyl)-3,5-pyrazinedicarboxylic acid, dimethyl ester

Product 1

HCID 98731274-[3-[[[[3-(4-Cyclohexyl-1-piperazinyl)propyl]amino]-carbonothioyl]amino]phenyl]-1,4-dihydro-2,6-dimethyl-3,5-pyrazinedicarboxylic acid, dimethyl esterYield 92%

Procedure

1,4-Dihydro-2,6-dimethyl-4-(3-isothiocyanatophenyl)-3,5-pyrazinedicarboxylic acid, dimethyl ester (500 mg, 1.4 mmol) was refluxed with 4-cyclohexyl-1-piperazine-1-propanamine (345 mg, 1.5 mmol) in 8 mL of benzene for 2 hours. Chromatographic purification (on silica gel, 100% methylene chloride first, followed by 10% (v/v) methanol in methylene chloride) of the residue after concentration in vacuo gave the title compound as a yellow foam (752 mg, 92%); 1H-NMR (CDCl3) δ 7.63 (br, 1H), 7.11 (t, 1H, J=8.0 Hz), 6.85 (br, 1H), 6.72 (br, 1H), 6.60 (d, 1H, J=8.2 Hz), 6.56 (dd, 1H, J=8.3, 2.2 Hz), 6.45 (br, 1H), 3.75 (s, 6H), 3.65 (m, 2H), 2.40 (s, 6H), 2.31 (t, 2H, J=6.6 Hz), 2.20-2.60 (m, 8H), 2.16 (m, 1H), 1.50-1.95 (m, 7H), 1.00-1.30 (m, 5H); 13C-NMR (CDCl3) δ 165.9, 152.5, 149.2, 130.1, 112.0, 108.8, 63.6, 53.2, 51.9, 48.7, 29.0, 26.2, 25.8, 25.3, and 18.0.

Workup

  1. customChromatographic purification (on silica gel, 100% methylene chloride first
  2. concentrationafter concentration in vacuo

Sources & evidence

ORD record
ord-424a496dfb234b7483715f170451b66b
Source dataset
uspto-grants-2001_01
Patent number
US06177429B1

Reaction notes

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