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 1162494Notes

Reaction equation

[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]

Participants

Conditions

Temperature: 90 °C

Procedure

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).

Workup

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

Sources & evidence

ORD record: ord-220279c15f1244469cbe71cea3d8c299
Source dataset: uspto-grants-2010_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07820665B2

Reaction notes

Loading…