Sodium Carbonate → 5-(2-amino-4-methoxycarbonylphenyl)-1-isobutyl-1H-imidazole-4-carbonitrile

HRID 574014Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 574014
C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.I[C:21]1[N:25]([CH2:26][CH:27]([CH3:29])[CH3:28])[CH:24]=[N:23][C:22]=1[C:30]#[N:31].Cl.[NH2:33][C:34]1[CH:39]=[C:38]([C:40]([O:42][CH3:43])=[O:41])[CH:37]=[CH:36][C:35]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.CC([O-])=O.CC([O-])=O.[Pd+2]>[NH2:33][C:34]1[CH:39]=[C:38]([C:40]([O:42][CH3:43])=[O:41])[CH:37]=[CH:36][C:35]=1[C:21]1[N:25]([CH2:26][CH:27]([CH3:29])[CH3:28])[CH:24]=[N:23][C:22]=1[C:30]#[N:31]

Komponenten

7

Edukt 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 164270832-Amino-4-(methoxycarbonyl)benzeneboronic acid hydrochlorideHCID 445414195-iodo-1-isobutyl-1H-imidazole-4-carbonitrile

Produkt 1

HCID 867279625-(2-amino-4-methoxycarbonylphenyl)-1-isobutyl-1H-imidazole-4-carbonitrileAusbeute 89 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a suspension of Pd(OAc)2 (11.2 mg, 0.05 mmol, 0.05 equiv) and PPh3 (26.2 mg, 0.1 mmol, 0.1 equiv) in DME (4 mL) were sequentially added 5-iodo-1-isobutyl-1H-imidazole-4-carbonitrile S5 (275 mg, 1 mmol, 1 equiv), 2-amino-4-methoxycarbonylphenyl-boronic acid hydrochloride salt (347 mg, 1.5 mmol, 1.5 equiv) and 1.5 M aqueous Na2CO3 (2.0 mL, 3.0 mmol, 3.0 equiv) at 25° C. The reaction was heated at 100° C. for 3 h. TLC and MS analysis indicated complete conversion of S5. The reaction was then cooled down to 25° C. and partitioned between EtOAc (50 mL) and H2O (10 mL). The aqueous layer was extracted with EtOAc (3×15 mL) and the combined organic layers were washed with saturated aqueous NaCl (20 mL), dried (MgSO4) and concentrated in vacuo. Purification by flash column chromatography on silica gel (1/9 EtOAc/hexanes-7/3 EtOAc/hexanes, gradient) afforded the title compound (265 mg, 89%) as a light yellow foam: 1H NMR (CDCl3, 600 Hz) δ 0.71 (d, J=9.6 Hz, 3H), 0.75 (d, J=9.6 Hz, 3H), 1.75 (hept, J=9.6 Hz, 1H), 3.64-3.67 (m, 2H), 3.90 (s, 3H), 7.15 (d, J=7.8 Hz, 1H), 7.44 (d, J=7.8 Hz), 7.45 (s, 1H), 7.57 (s, 1H); 13C NMR (CDCl3, 150 Hz) δ 19.6, 19.7, 29.5, 52.3, 53.6, 117.0, 128.4, 128.5, 131.7, 131.9, 131.9, 132.0, 132.1, 133.2, 139.8, 166.5; LRMS (ESI+): calcd C16H19N4O2 [M+H]+299.2. found 299.1.

Aufarbeitung

  1. customat 25° C
  2. temperatureThe reaction was then cooled down to 25° C.
  3. custompartitioned between EtOAc (50 mL) and H2O (10 mL)
  4. extractionThe aqueous layer was extracted with EtOAc (3×15 mL)
  5. washthe combined organic layers were washed with saturated aqueous NaCl (20 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customPurification by flash column chromatography on silica gel (1/9 EtOAc/hexanes-7/3 EtOAc/hexanes, gradient)

Quellen und Nachweise

ORD-Eintrag
ord-e1eb5b2924c047938a1ff30d64a794ff
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09034336B2

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