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

HRID 1776665Notes

Reaction equation

HRID 1776665 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([N+:7]([O-])=O)[CH:4]=[C:3]1[C:10]([O:12][CH3:13])=[O:11].Cl.[H][H].[CH3:17][N:18]1[CH:22]=[C:21]([N+:23]([O-:25])=[O:24])[CH:20]=[C:19]1[C:26]([OH:28])=O.C(Cl)CCl.CCN(C(C)C)C(C)C>[Pd].CC(N(C)C)=O.C1COCC1>[CH3:1][N:2]1[CH:6]=[C:5]([NH:7][C:26]([C:19]2[N:18]([CH3:17])[CH:22]=[C:21]([N+:23]([O-:25])=[O:24])[CH:20]=2)=[O:28])[CH:4]=[C:3]1[C:10]([O:12][CH3:13])=[O:11]

Participants

10

Reactant 6

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 27369151-Methyl-4-nitropyrrole-2-carboxylic acidHCID 2759930Methyl 1-methyl-4-nitro-1H-pyrrole-2-carboxylateHCID 178418361HCID 178418361, compound

Product 1

HCID 592893Methyl 1-methyl-4-(1-methyl-4-nitropyrrole-2-carboxamido)pyrrole-2-carboxylateYield 75.5%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent

Procedure

In a hydrogenation bottle was added methyl 1-methyl-4-nitro-1H-pyrrole-2-carboxylate (3.0 g, 16.30 mmol), 80 ml of THF, 405 mg of 10% Pd/C and 1.3 ml of HCl (conc.). After evacuation under vacuum the bottle was placed under 30 psi hydrogen and shaken for 5 hours. The mixture was filtered through celites, evaporated to dryness without further purification. To the dry mixture was added 1-methyl-4-nitro-1H-pyrrole-2-carboxylic acid (2.75 g, 16.18 mmol), 80 ml of DMA, EDC (8.51 g, 44.27 mmol) and DIPEA (2.80 ml, 16.10 mmol). The mixture was stirred under Ar overnight, concentrated, diluted with THF/EtAc (1:2, 150 ml), and washed 1M NaH2PO4/NaCl (conc) and NaHCO3 (conc) separately. The organic layer was separated and dried over MgSO4, filtered concentrated and crystallized with THF/H2O to afford 3.74 g (75%) of the title product. 1H NMR (DMSO) 10.25 (s, 1H), 8.17 (s, 1H), 7.25 (s, 1H), 6.52 (s, 1H), 6.08 (s, 1H), 3.90 (s, 3H), 3.78 (s, 3H), 3.56 (s, 3H); 13C NMR 157.87, 156.84, 133.76, 128.16, 123.39, 119.13, 118.18, 111.83, 107.50, 104.17, 51.55, 37.41, 36.03; MS m/z+329.1 (M+Na).

Workup

  1. filtrationThe mixture was filtered through celites
  2. customevaporated to dryness without further purification
  3. stirringThe mixture was stirred under Ar overnight
  4. concentrationconcentrated
  5. additiondiluted with THF/EtAc (1:2, 150 ml)
  6. washwashed 1M NaH2PO4/NaCl (conc) and NaHCO3 (conc) separately
  7. customThe organic layer was separated
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customcrystallized with THF/H2O

Sources & evidence

ORD record
ord-b77fde3b1c6543418b26972bbab1ae20
Source dataset
uspto-grants-2016_02
Patent number
US09265841B2

Reaction notes

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