1,2-Dichloroethane → Methyl 1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxylate

HRID 1776671Notes

Reaction equation

HRID 1776671 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([NH:7][C:8]([C:10]2[N:11]([CH3:18])[CH:12]=[C:13]([N+:15]([O-])=O)[CH:14]=2)=[O:9])[CH:4]=[C:3]1[C:19]([O:21][CH3:22])=[O:20].Cl.[H][H].[CH3:26][N:27]1[CH:31]=[C:30]([NH:32][C:33]([C:35]2[N:36]([CH3:43])[CH:37]=[C:38]([N+:40]([O-:42])=[O:41])[CH:39]=2)=[O:34])[CH:29]=[C:28]1[C:44]([OH:46])=O.C(Cl)CCl.CCN(C(C)C)C(C)C>[Pd].CC(N(C)C)=O>[CH3:1][N:2]1[CH:6]=[C:5]([NH:7][C:8]([C:10]2[N:11]([CH3:18])[CH:12]=[C:13]([NH:15][C:44]([C:28]3[N:27]([CH3:26])[CH:31]=[C:30]([NH:32][C:33]([C:35]4[N:36]([CH3:43])[CH:37]=[C:38]([N+:40]([O-:42])=[O:41])[CH:39]=4)=[O:34])[CH:29]=3)=[O:46])[CH:14]=2)=[O:9])[CH:4]=[C:3]1[C:19]([O:21][CH3:22])=[O:20]

Participants

9

Reactant 6

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 4041101-Methyl-4-(1-methyl-4-nitropyrrole-2-carboxamido)pyrrole-2-carboxylic acidHCID 592893Methyl 1-methyl-4-(1-methyl-4-nitropyrrole-2-carboxamido)pyrrole-2-carboxylateHCID 178418361HCID 178418361, compound

Product 1

HCID 59440204Methyl 1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxylateYield 76%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 31374DimethylacetamideSolvent2×

Procedure

In a hydrogenation bottle was added methyl 1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxylate (2.0 g, 6.53 mmol), 80 ml of DMA, 500 mg of 10% Pd/C (50% wet) and 0.4 ml of HCl (conc.). After evacuation under vacuum, the bottle was placed under 50 psi hydrogen and shaken for 4 hours. The mixture was filtered through celite, evaporated to dryness without further purification. To the dry mixture was added 1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxylic acid (1.49 g, 5.10 mmol), 30 ml of DMA, EDC (4.0 g, 20.8 mmol) and DIPEA (1.0 ml, 5.75 mmol). The mixture was stirred under Ar overnight, concentrated, diluted with Hexane/EtAc (1:1, 10 ml) and water 10 ml to form precipitates. The precipitates were filtered, washed 1M NaH2PO4, 1 M NaHCO3 and water, dried over P2O5 under vacuum to afford 2.13 g (76%) of the title product. 1H NMR (DMSO) 10.28 (s, 1H), 10.25 (s, 1H), 9.78 (s, 1H), 8.18 (s, 1H), 7.86 (s, 1H), 7.52 (s, 1H), 7.31 (d, 1H, J=1.7 Hz), 7.25 (s, 1H), 7.23 (s, 1H), 7.17 (d, 1H, J=1.5 Hz), 6.98 (s, 1H), 6.71 (s, 1H), 4.02 (s, 3H), 3.94 (s, 3H), 3.83 (s, 3H), 3.73 (s, 3H), 3.56 (s, 3H), 1.47 (s, 9H); 13C NMR 160.78, 158.93, 158.06, 157.81, 135.25, 127.28, 126.36, 123.78, 122.57, 121.91, 121.40, 120.94, 119.65, 110.73, 108.39, 107.34, 103.75, 80.81, 51.57, 39.74, 38.52, 38.22, 37.08, 28.63; MS m/z+573.2 (M+Na).

Workup

  1. filtrationThe mixture was filtered through celite
  2. customevaporated to dryness without further purification
  3. stirringThe mixture was stirred under Ar overnight
  4. concentrationconcentrated
  5. additiondiluted with Hexane/EtAc (1:1, 10 ml) and water 10 ml
  6. customto form
  7. customprecipitates
  8. filtrationThe precipitates were filtered
  9. washwashed 1M NaH2PO4, 1 M NaHCO3 and water
  10. dry with materialdried over P2O5 under vacuum

Sources & evidence

ORD record
ord-37be948e9c9642beb4c7fadb5cbf9680
Source dataset
uspto-grants-2016_02
Patent number
US09265841B2

Reaction notes

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