1,4-Dihydro-2,6-dimethyl-4-(3-isothiocyanatophenyl)-3,5-pyrazinedicarboxylic acid, dimethyl ester → 1,4-Dihydro-2,6-dimethyl-4-[3-[[[[3-[4-(1,1-dimethylethyl)-1-piperidinyl]propyl]amino]carbonothioyl]amino]phenyl]-3,5-pyrazine dicarboxylic acid, dimethyl ester

HRID 566905Notes

Reaction equation

HRID 566905 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].[C:26]([CH:30]1[CH2:35][CH2:34][N:33]([CH2:36][CH2:37][CH2:38][NH2:39])[CH2:32][CH2:31]1)([CH3:29])([CH3:28])[CH3:27]>C1C=CC=CC=1>[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]([NH:18][C:19]([NH:39][CH2:38][CH2:37][CH2:36][N:33]3[CH2:32][CH2:31][CH:30]([C:26]([CH3:29])([CH3:28])[CH3:27])[CH2:35][CH2:34]3)=[S:20])[CH:13]=2)[C:7]=1[C:8]([O:10][CH3:11])=[O:9]

Participants

4

Reactant 2

HCID 155242381,4-Dihydro-2,6-dimethyl-4-(3-isothiocyanatophenyl)-3,5-pyrazinedicarboxylic acid, dimethyl esterHCID 212639684-Tert-butyl-piperidine-1-propanamine

Product 1

HCID 98724581,4-Dihydro-2,6-dimethyl-4-[3-[[[[3-[4-(1,1-dimethylethyl)-1-piperidinyl]propyl]amino]carbonothioyl]amino]phenyl]-3,5-pyrazine dicarboxylic acid, dimethyl esterYield 64%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

1,4-Dihydro-2,6-dimethyl-4-(3-isothiocyanatophenyl)-3,5-pyrazinedicarboxylic acid, dimethyl ester (25 mg, 0.069 mmol) was refluxed with 4-tert-butyl-piperidine-1-propanamine (16 mg, 0.081 mmol) in 2 mL of benzene for 30 min. Chromatographic purification (silica gel, eluted with 10% (v/v) methanol in methylene chloride) of the resultant residue after concentration in vacuo gave the title compound as a yellow powder (64%); 1H-NMR (CDCl3) δ 8.20 (br, 1H), 7.98 (br, 1H), 7.05 (t, 1H, J=8.1 Hz), 6.79 (br, 1H), 6.66 (d, 1H, J=8.0 Hz), 6.50-6.60 (m, 2H), 3.70 (s, 6H), 3.55 (m, 2H), 3.28 (m, 2H), 2.72 (m, 2H), 2.30-2.55 (m, 2H), 2.37 (s, 6H), 1.86 (m, 2H), 1.50-1.80 (m, 2H), 0.95-1.25 (m, 1H), and 0.79 (s, 6H); 13C-NMR (CDCl3) δ 180.9, 166.3, 152.8, 150.1, 129.9, 116.3, 112.7, 109.9, 108.5, 53.9, 51.8, 44.9, 42.1, 32.1, 29.8, 27.2, 24.7, 24.5, and 17.8.

Workup

  1. customChromatographic purification (silica gel, eluted with 10% (v/v) methanol in methylene chloride) of the resultant residue
  2. concentrationafter concentration in vacuo

Sources & evidence

ORD record
ord-6aefb4a8a5a246d89560f90abfca06a7
Source dataset
uspto-grants-2001_01
Patent number
US06177429B1

Reaction notes

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