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 1776670Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1776670
[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]

Komponenten

10

Edukt 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, Verbindung

Produkt 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-carboxylateAusbeute 82 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 23938PalladiumKatalysatorHCID 8028TetrahydrofuranLösungsmittelHCID 31374DimethylacetamideLösungsmittel

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-37277968673645079e10dfaa09cb13fe
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09265841B2

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