1,2-Dichloroethane → tert-butyl 4-(1-(1-(benzyloxycarbonyl)piperidin-3-yl)-2-oxo-5-phenyl-2,3-dihydro-1H-imidazole-4-carbonyl)piperazine-1-carboxylate

HRID 1685121Notes

Reaction equation

HRID 1685121 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH2:14][CH:13]([N:17]2[C:21]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[C:20]([C:28](O)=[O:29])[NH:19][C:18]2=[O:31])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[N:55]1([C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])[CH2:60][CH2:59][NH:58][CH2:57][CH2:56]1>CN(C=O)C.O>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH2:14][CH:13]([N:17]2[C:21]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[C:20]([C:28]([N:58]3[CH2:57][CH2:56][N:55]([C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])[CH2:60][CH2:59]3)=[O:29])[NH:19][C:18]2=[O:31])[CH2:12]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 592924061-(1-(benzyloxycarbonyl)piperidin-3-yl)-2-oxo-5-phenyl-2,3-dihydro-1H-imidazole-4-carboxylic acid2×

Product 1

HCID 24999588tert-butyl 4-(1-(1-(benzyloxycarbonyl)piperidin-3-yl)-2-oxo-5-phenyl-2,3-dihydro-1H-imidazole-4-carbonyl)piperazine-1-carboxylateYield 76.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Dissolved 16E (3.0 g, 7.118 mmol) prepared in the previous step in 30 mL of DMF and added EDC (2.39 g, 12.46 mmol) and HOBt (1.65 g, 12.01 mmol). The mixture was stirred for at least 15 minutes. Next, DIEA (2.76 mL, 21.35 mmol) was added along with tert-butyl piperazine-1-carboxylate (1.39 g, 7.47 mmol). This reaction mixture was then stirred at RT for about four hours. After the disappearance of 16E, this mixture was poured into 300 mL of water, a white precipitate was formed. The white solid was filtered, rinsed with water and dried under vacuum to provide tert-butyl 4-(1-(1-(benzyloxycarbonyl)piperidin-3-yl)-2-oxo-5-phenyl-2,3-dihydro-1H-imidazole-4-carbonyl)piperazine-1-carboxylate (16F) (3.2 g, 76%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.34 (s, 9H) 1.40 (s, 2H) 1.65-1.80 (m, 4H) 2.34 (br. s., 1H) 2.83 (br. s., 4H) 3.13-3.19 (m, 4H) 3.94-4.07 (m, 2H) 5.03 (s, 2H) 7.23-7.50 (m, 10H) 10.73 (s, 1H). ESI-MS: m/z 590.1 (M+H)+.

Workup

  1. stirringThis reaction mixture was then stirred at RT for about four hours
  2. customa white precipitate was formed
  3. filtrationThe white solid was filtered
  4. washrinsed with water
  5. customdried under vacuum

Sources & evidence

ORD record
ord-bffb24675afb4b33bd0893a13d30fc2b
Source dataset
uspto-grants-2012_04
Patent number
US08148367B2

Reaction notes

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