1,2-Dichloroethane → Methyl 4-(4-(4-(4-(tert-butoxycarbonylamino)-1-methyl-1H-pyrrole-2-carboxamido)-1-methyl-1H-imidazole-2-carboxamido)-1-methyl-1H-pyrrole-2-carboxamido)-1-methyl-1H-pyrrole-2-carboxylate

HRID 2403494Notes

Reaction equation

HRID 2403494 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].[C:26]([O:30][C:31]([NH:33][C:34]1[CH:35]=[C:36]([C:40]([NH:42][C:43]2[N:44]=[C:45]([C:49](O)=[O:50])[N:46]([CH3:48])[CH:47]=2)=[O:41])[N:37]([CH3:39])[CH:38]=1)=[O:32])([CH3:29])([CH3:28])[CH3:27].C(Cl)CCl.CCN(C(C)C)C(C)C>[Pd].CC(N(C)C)=O.C1COCC1>[C:26]([O:30][C:31]([NH:33][C:34]1[CH:35]=[C:36]([C:40]([NH:42][C:43]2[N:44]=[C:45]([C:49]([NH:15][C:13]3[CH:14]=[C:10]([C:8]([NH:7][C:5]4[CH:4]=[C:3]([C:19]([O:21][CH3:22])=[O:20])[N:2]([CH3:1])[CH:6]=4)=[O:9])[N:11]([CH3:18])[CH:12]=3)=[O:50])[N:46]([CH3:48])[CH:47]=2)=[O:41])[N:37]([CH3:39])[CH:38]=1)=[O:32])([CH3:29])([CH3:27])[CH3:28]

Participants

10

Reactant 6

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 592893Methyl 1-methyl-4-(1-methyl-4-nitropyrrole-2-carboxamido)pyrrole-2-carboxylateHCID 27611954-(4-((tert-Butoxycarbonyl)amino)-1-methyl-1H-pyrrole-2-carboxamido)-1-methyl-1H-imidazole-2-carboxylic acidHCID 178418361HCID 178418361, compound

Product 1

HCID 59440139Methyl 4-(4-(4-(4-(tert-butoxycarbonylamino)-1-methyl-1H-pyrrole-2-carboxamido)-1-methyl-1H-imidazole-2-carboxamido)-1-methyl-1H-pyrrole-2-carboxamido)-1-methyl-1H-pyrrole-2-carboxylateYield 82%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent

Procedure

In a hydrogenation bottle was added methyl 1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxylate (1.0 g, 3.27 mmol), 20 ml of THF, 305 mg of 10% Pd/C (50% wet) and 0.25 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 dried mixture was added 4-(4-(tert-butoxycarbonylamino)-1-methyl-1H-pyrrole-2-carboxamido)-1-methyl-1H-imidazole-2-carboxylic acid (1.15 g, 3.16 mmol), 10 ml of DMA, EDC (2.0 g, 10.4 mmol) and DIPEA (0.70 ml, 4.02 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 with vacuum to afford 1.61 g (82%) of the title product. 1H NMR (DMF-d7) 10.29 (s, 1H), 10.20 (s, 1H), 10.12 (s, 1H), 9.08 (s, 1H), 7.58 (s, 1H), 7.47 (d, 1H, J=1.7 Hz), 7.26 (d, 1H, J=1.5 Hz), 7.15 (d, 1H, J=1.5 Hz), 6.98 (s, 1H), 6.91 (d, 1H, J=1.8 Hz), 6.86 (s, 1H), 3.97 (s, 3H), 3.82 (s, 3H), 3.73 (s, 3H), 3.56 (s, 3H), 1.45 (s, 9H); 13C NMR 162.16, 160.05, 159.90, 157.20, 154.31, 137.88, 135.35, 124.56, 124.39, 124.24, 123.09, 120.09, 119.82, 115.32, 105.58, 102.27, 79.31, 51.51, 38.13, 36.01, 35.80, 35.08, 28.79; MS m/z+644.2 (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 with vacuum

Sources & evidence

ORD record
ord-71d956298ba645dbaf538d184dd3f7cb
Source dataset
uspto-grants-2014_08
Patent number
US08802667B2

Reaction notes

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