Sodium Carbonate → N-(6-(6-chloro-5-(3-(difluoromethoxy)phenylsulfonamido)pyridin-3-yl)-3-(pyridin-4-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide

HRID 1162488Notes

Reaction equation

HRID 1162488 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][C:39](B(O)O)=[CH:38][CH:37]=1.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1>[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].O>[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:39]4[CH:40]=[CH:41][N:36]=[CH:37][CH:38]=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

7

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 2734379(Pyridin-4-yl)boronic acidHCID 57749431N-(6-(6-chloro-5-(3-(difluoromethoxy)phenylsulfonamido)pyridin-3-yl)-3-iodoimidazo[1,2-b]pyridazin-2-yl)acetamide

Product 1

HCID 44125126N-(6-(6-chloro-5-(3-(difluoromethoxy)phenylsulfonamido)pyridin-3-yl)-3-(pyridin-4-yl)imidazo[1,2-b]pyridazin-2-yl)acetamideYield 56.3%

Reagents, catalysts & solvents 2

HCID 178478230HCID 178478230, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
80 °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 (129.0 mg, 203 μmol), 4-pyridylboronic acid (30.0 mg, 244 μmol, Alfa Aesar, Ward Hill, Mass.), sodium carbonate (86.2 mg, 813 μmol), and dichloro 1,1′-bis(diphenylphosphino)ferrocene palladium(II) (11.3 mg, 20.3 μmol, Strem Chemical, Inc., Newburyport, Mass.). The vial was sealed with a septum cap, and 1,4-dioxane (2 mL) was added under positive N2 flow followed by water (0.2 mL). The mixture was sparged with N2 for 10 min and then heated at 80° C. for 18 h. The solution was cooled to rt and absorbed directly onto a 25 g silica loading cartridge and passed through a Redi-Sep® pre-packed silica gel column (80 g) (Teledyne Isco, Lincoln, Nebr.) 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-4-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide (67.0 mg, 56.3% yield) as a yellow solid. LCMS (ESI positive ion) m/z: 586 (M+1); 1H NMR (400 MHz, MeOH) δ ppm 2.21 (s, 3H); 6.61-6.97 (m, 1H); 7.33-7.40 (m, 1H); 7.48 (t, J=8.07 Hz, 1H); 7.56 (s, 1H); 7.95 (d, J=9.49 Hz, 1H); 8.06 (d, J=4.99 Hz, 2H); 8.17 (d, J=9.49 Hz, 1H); 8.67-8.74 (m, 2H); 8.80 (d, J=1.96 Hz, 2H).

Workup

  1. customThe vial was sealed with a septum
  2. customcap
  3. customThe mixture was sparged with N2 for 10 min
  4. temperatureThe solution was cooled to rt
  5. customabsorbed directly onto a 25 g silica loading cartridge

Sources & evidence

ORD record
ord-e3d20cd9cf724421a8ffeddddb97f9ec
Source dataset
uspto-grants-2010_10
Patent number
US07820665B2

Reaction notes

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