Triethylamine → 4-[3-[[[[3-[4-(3-Methoxyphenyl)-1-piperidinyl]propyl]amino]-carbonyl]amino]phenyl]-1,4-dihydro-2,6-dimethyl-3,5-pyrazinedicarboxylic acid, dimethyl ester

HRID 566908Notes

Reaction equation

HRID 566908 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([N:8]2[C:13]([C:14]([O:16][CH3:17])=[O:15])=[C:12]([CH3:18])[NH:11][C:10]([CH3:19])=[C:9]2[C:20]([O:22][CH3:23])=[O:21])[CH:5]=[CH:6][CH:7]=1.[C:24](N1C=CN=C1)(N1C=CN=C1)=[O:25].C(N(CC)CC)C.[CH3:43][O:44][C:45]1[CH:46]=[C:47]([CH:51]2[CH2:56][CH2:55][N:54]([CH2:57][CH2:58][CH2:59][NH2:60])[CH2:53][CH2:52]2)[CH:48]=[CH:49][CH:50]=1>CN(C=O)C>[CH3:43][O:44][C:45]1[CH:46]=[C:47]([CH:51]2[CH2:56][CH2:55][N:54]([CH2:57][CH2:58][CH2:59][NH:60][C:24]([NH:1][C:2]3[CH:3]=[C:4]([N:8]4[C:9]([C:20]([O:22][CH3:23])=[O:21])=[C:10]([CH3:19])[NH:11][C:12]([CH3:18])=[C:13]4[C:14]([O:16][CH3:17])=[O:15])[CH:5]=[CH:6][CH:7]=3)=[O:25])[CH2:53][CH2:52]2)[CH:48]=[CH:49][CH:50]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 120432914-(3-Methoxyphenyl)piperidine-1-propanamineHCID 155242374-(3-Aminophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyrazinedicarboxylic acid, dimethyl ester

Product 1

HCID 99165324-[3-[[[[3-[4-(3-Methoxyphenyl)-1-piperidinyl]propyl]amino]-carbonyl]amino]phenyl]-1,4-dihydro-2,6-dimethyl-3,5-pyrazinedicarboxylic acid, dimethyl esterYield 72%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-(3-Aminophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyrazinedicarboxylic acid, dimethyl ester (150 mg, 0.47 mmol) was slowly added into a mixture of 1,1′-carbonyidiimidazole (117 mg, 0.72 mmol) and triethylamine (145 mg, 1.44 mmol) in 5 mL of DMF and the reaction mixture was stirred for 60 min. 4-(3-Methoxyphenyl)piperidine-1-propanamine (176 mg, 0.69 mmol) was added to the reaction mixture, and the reaction was stirred at room temperature for 30 min. DMF was removed in vacuo and the residue was purified by chromatography (on silica gel, 10% (v/v) methanol in methylene chloride then followed by 2M ammonia in methanol) to give the title compound as an orange foam (200 mg, 72%); 1H-NMR (CDCl3) δ 7.55 (br, 1H), 7.35 (br, 1H), 7.20 (t, 1H, J=7.6 Hz), 6.92 (t, 1H, J=8.1 Hz), 6.60-6.80 (m, 4H), 6.54 (d, 1H, J=7.6 Hz), 6.32 (dd, 1H, J=8.2, 2.0 Hz), 5.99 (br, 1H), 3.77 (s, 3H), 3.71 (s, 6H), 3.16 (m, 2H), 3.03 (m, 2H), 2.46 (m, 3H), 2.29 (s, 6H), 1.95-2.20 (m, 2H), 1.60-1.90 (m, 6H); 13C-NMR (CDCl3) δ 166.6, 159.7, 156.8, 151.9, 149.7, 147.4, 139.4, 129.5, 129.2, 119.3, 112.9, 111.4, 108.9, 108.5, 106.1, 56.0, 55.2, 54.1, 51.7, 42.2, 38.6, 32.8, 26.8, and 17.6.

Workup

  1. stirringthe reaction was stirred at room temperature for 30 min
  2. customDMF was removed in vacuo
  3. customthe residue was purified by chromatography (on silica gel, 10% (v/v) methanol in methylene chloride

Sources & evidence

ORD record
ord-e4793f27dbd04c8e830ce02db49e2796
Source dataset
uspto-grants-2001_01
Patent number
US06177429B1

Reaction notes

Loading…