Sodium Carbonate → N-(6-(6-chloro-5-(3-(difluoromethoxy)phenylsulfonamido)pyridin-3-yl)-3-(pyridin-3-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide

HRID 1162494Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1162494
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]3[N:12]([C:14](I)=[C:15]([NH:17][C:18](=[O:20])[CH3:19])[N:16]=3)[N:13]=2)=[CH:4][C:3]=1[NH:22][S:23]([C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([O:32][CH:33]([F:35])[F:34])[CH:27]=1)(=[O:25])=[O:24].[N:36]1[CH:41]=[CH:40][CH:39]=[C:38](B(O)O)[CH:37]=1.C(=O)([O-])[O-].[Na+].[Na+]>[Pd+2].ClC1C=C[C-](P(C2C=CC=CC=2)C2C=CC=CC=2)C=1Cl.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O1CCOCC1>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]3[N:12]([C:14]([C:38]4[CH:37]=[N:36][CH:41]=[CH:40][CH:39]=4)=[C:15]([NH:17][C:18](=[O:20])[CH3:19])[N:16]=3)[N:13]=2)=[CH:4][C:3]=1[NH:22][S:23]([C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([O:32][CH:33]([F:35])[F:34])[CH:27]=1)(=[O:25])=[O:24]

Komponenten

6

Edukt 3

HCID 10340Sodium CarbonateHCID 27343783-Pyridinylboronic acidHCID 57749431N-(6-(6-chloro-5-(3-(difluoromethoxy)phenylsulfonamido)pyridin-3-yl)-3-iodoimidazo[1,2-b]pyridazin-2-yl)acetamide

Produkt 1

HCID 44124987N-(6-(6-chloro-5-(3-(difluoromethoxy)phenylsulfonamido)pyridin-3-yl)-3-(pyridin-3-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178478230HCID 178478230, VerbindungKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A sealable vial was charged with N-(6-(6-chloro-5-(3-(difluoromethoxy)phenylsulfonamido)pyridin-3-yl)-3-iodoimidazo[1,2-b]pyridazin-2-yl)acetamide (27.0 mg, 42.5 μmol), 3-pyridylboronic acid (6.27 mg, 51.0 μmol), and dichloro 1,1′-bis(diphenylphosphino)ferrocene palladium(II) (2.36 mg, 4.25 μmol). The vial was sealed and 1,4-dioxane (1 mL) was added under positive N2 flow. Then an aqueous solution of sodium carbonate (1.9 M, 89.5 μl, 170 μmol) was added via syringe. The resulting solution was sparged with N2 for 10 minutes, then heated at 90° C. for 18 h. The solution was cooled to rt and directly absorbed onto a 5 g silica loading cartridge and passed through a Redi-Sep® pre-packed silica gel column (Teledyne Isco, Lincoln, Nebr.) (12 g) using a gradient of 1% MeOH in CH2Cl2 to 10% MeOH in CH2Cl2 to afford the title compound N-(6-(6-chloro-5-(3-(difluoromethoxy)phenylsulfonamido)pyridin-3-yl)-3-(pyridin-3-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide as a yellow solid. LCMS (ESI positive ionization) m/z: 586 (M+1); 1H NMR (400 MHz, MeOH) δ ppm 2.18 (s, 3H); 6.81 (t, J=73.11 Hz, 1H); 7.32-7.40 (m, 1H); 7.48 (t, J=8.02 Hz, 1H); 7.53-7.57 (m, 1H); 7.58-7.63 (m, 1H); 7.67 (dd, J=7.87, 5.04 Hz, 1H); 7.90 (d, J=9.49 Hz, 1H); 8.15 (d, J=9.49 Hz, 1H); 8.47 (d, J=8.02 Hz, 1H); 8.60 (d, J=3.52 Hz, 1H); 8.64 (d, J=2.25 Hz, 1H); 8.77 (d, J=2.25 Hz, 1H); 8.97 (s, 1H).

Aufarbeitung

  1. customThe vial was sealed
  2. customThe resulting solution was sparged with N2 for 10 minutes
  3. temperatureThe solution was cooled to rt
  4. customdirectly absorbed onto a 5 g silica loading cartridge

Quellen und Nachweise

ORD-Eintrag
ord-220279c15f1244469cbe71cea3d8c299
Quelldatensatz
uspto-grants-2010_10
Patentnummer
US07820665B2

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