Sodium Carbonate → 3-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-(3-pyridinyl)thieno[3,2-c]pyridin-4-amine

HRID 1909929Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1909929
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH2:9][C:10]([N:12]1[C:20]2[C:15](=[CH:16][C:17]([C:21]3[C:25]4[C:26]([NH2:31])=[N:27][CH:28]=[C:29](I)[C:24]=4[S:23][CH:22]=3)=[CH:18][CH:19]=2)[CH2:14][CH2:13]1)=[O:11].[N:32]1[CH:37]=[CH:36][CH:35]=[C:34](B(O)O)[CH:33]=1.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1>C(OCC)(=O)C.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH2:9][C:10]([N:12]1[C:20]2[C:15](=[CH:16][C:17]([C:21]3[C:25]4[C:26]([NH2:31])=[N:27][CH:28]=[C:29]([C:34]5[CH:33]=[N:32][CH:37]=[CH:36][CH:35]=5)[C:24]=4[S:23][CH:22]=3)=[CH:18][CH:19]=2)[CH2:14][CH2:13]1)=[O:11]

Komponenten

7

Edukt 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 27343783-Pyridinylboronic acidHCID 668236633-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-iodothieno[3,2-c]pyridin-4-amine

Produkt 1

HCID 534678203-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-(3-pyridinyl)thieno[3,2-c]pyridin-4-amineAusbeute 82 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

To a 25 mL microwave reaction tube was charged 3-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-iodothieno[3,2-c]pyridin-4-amine (150 mg, 0.274 mmol), 3-pyridinylboronic acid (33.7 mg, 0.274 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (11.19 mg, 0.014 mmol), and sodium carbonate (58.1 mg, 0.548 mmol) followed by dioxane (5 mL), and water (1 mL). The reaction was heated at 120° C. for 30 min in microwave reactor. Ethyl acetate (20 mL) was added and the layers were separated. The organic layer was washed with brine, concentrated, and the residue purified by silica gel chromatography (0%-100% EtOAc in hexanes). Product came out at 100% EtOAc, the fractions with the product was combined, evaporated to dryness to afford the title compound as a light gray solid (112 mg). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.88 (d, J=2.0 Hz, 1H) 8.62 (dd, J=4.8, 1.3 Hz, 1H) 8.04-8.18 (m, 2H) 7.97 (s, 1H) 7.56 (dd, J=7.6, 4.8 Hz, 1H) 7.51 (s, 1H) 7.39 (s, 1H) 7.14-7.32 (m, 4H) 5.64 (br. s., 2H) 4.32 (t, J=8.3 Hz, 2H) 3.97 (s, 2H) 3.29 (t, 2H).

Aufarbeitung

  1. customthe layers were separated
  2. washThe organic layer was washed with brine
  3. concentrationconcentrated
  4. customthe residue purified by silica gel chromatography (0%-100% EtOAc in hexanes)
  5. customevaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-5d7f10dd82634210a304896caeda0807
Quelldatensatz
uspto-grants-2013_12
Patentnummer
US08598156B2

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