Morpholine → (S)-4-(1-Benzyl-2-hydroxy-ethylamino)-3-(4-methyl-6-morpholin-4-yl-1H-benzimidazol-2-yl)-1H-pyridin-2-one

HRID 1793745Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1793745
[CH2:1]([C@H:8]([NH:30][C:31]1[CH:36]=[CH:35][NH:34][C:33](=[O:37])[C:32]=1[C:38]1[NH:42][C:41]2[CH:43]=[C:44](Br)[CH:45]=[C:46]([CH3:47])[C:40]=2[N:39]=1)[CH2:9][O:10]C(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:49]1[CH2:54][CH2:53][O:52][CH2:51][CH2:50]1.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.CC(C)([O-])C.[Na+].O1CCOCC1.Cl>C1(C)C=CC=CC=1.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([C@H:8]([NH:30][C:31]1[CH:36]=[CH:35][NH:34][C:33](=[O:37])[C:32]=1[C:38]1[NH:42][C:41]2[CH:43]=[C:44]([N:49]3[CH2:54][CH2:53][O:52][CH2:51][CH2:50]3)[CH:45]=[C:46]([CH3:47])[C:40]=2[N:39]=1)[CH2:9][OH:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Komponenten

9

Edukt 5

HCID 8083MorpholineHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 204431481,4-Dioxane hydrochlorideHCID 23676156Sodium t-butoxideHCID 136365126(S)-4-(1-benzyl-2-trityloxy-ethylamino)-3-[6-bromo-4-methyl-1H-benzimidazole-2-yl]-1H-pyridin-2-one

Produkt 1

HCID 136191255(S)-4-(1-Benzyl-2-hydroxy-ethylamino)-3-(4-methyl-6-morpholin-4-yl-1H-benzimidazol-2-yl)-1H-pyridin-2-oneAusbeute 18,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 1140TolueneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of (S)-4-(1-benzyl-2-trityloxy-ethylamino)-3-[6-bromo-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one (150 mg, 0.216 mmol), morpholine (28.2 mg, 0.324 mmol), palladium acetate (2.4 mg, 0.01 mmol), tri-tert-buylphosphine (4.4 mg, 0.02 mmol), and sodium tert-butoxide (104 mg, 1.08 mmol) in toluene (5 mL) was heated to 100° C. for 14 h under nitrogen. The reaction mixture was cooled to room temperature and diluted with EtOAc. After extraction, the combined organic layers were washed with water, brine, dried over Na2SO4. Concentration gave a brownish residue, which was treated with 4 N HCl dioxane solution (3 mL) at room temperature for 6 h. After removal of the solvent, the residue was purified by prep. HPLC to yield the title compound (18 mg, 18%). 1H NMR (400 MHz, CD3OD) δ 7.59 (1H, s), 7.12–7.28 (7H, m), 6.12 (1H, d, J=7.6 Hz), 4.01–4.08 (5H, m), 3.76 (1H, dd, J=4.8, 11.1 Hz), 3.71 (1H, dd, J=5.2, 11.1 Hz), 3.32–3.10 (4H, m), 3.09 (1H, dd, J=5.6, 13.7 Hz), 2.92 (1H, dd, J=8.0, 13.7 Hz), 2.65 (3H, s). LCMS (M+H)+ m/z 460 (t=1.30 min.).

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionAfter extraction
  3. washthe combined organic layers were washed with water, brine
  4. dry with materialdried over Na2SO4
  5. concentrationConcentration
  6. customgave a brownish residue, which
  7. customAfter removal of the solvent
  8. customthe residue was purified by prep

Quellen und Nachweise

ORD-Eintrag
ord-68323d92230442dfaae55347f4251932
Quelldatensatz
uspto-grants-2006_07
Patentnummer
US07081454B2

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