Sodium Carbonate → HCID 44125257, compound

HRID 1162475Notes

Reaction equation

HRID 1162475 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:9][S:10]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([OH:22])([CH3:21])[CH3:20])=[CH:15][CH:14]=2)(=[O:12])=[O:11])[C:5]([Cl:8])=[N:6][CH:7]=1.CC1(C)C(C)(C)OB([C:31]2[CH:32]=[CH:33][C:34]3[N:35]([CH:37]=[C:38]([NH:40][C:41](=[O:43])[CH3:42])[N:39]=3)[N:36]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O1CCOCC1>[Cl:8][C:5]1[N:6]=[CH:7][C:2]([C:31]2[CH:32]=[CH:33][C:34]3[N:35]([CH:37]=[C:38]([NH:40][C:41](=[O:43])[CH3:42])[N:39]=3)[N:36]=2)=[CH:3][C:4]=1[NH:9][S:10]([C:13]1[CH:18]=[CH:17][C:16]([C:19]([OH:22])([CH3:21])[CH3:20])=[CH:15][CH:14]=1)(=[O:12])=[O:11]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 57749440N-(6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2-b]pyridazin-2-yl)acetamideHCID 59519512N-(5-Bromo-2-chloro-3-pyridinyl)-4-(1-hydroxy-1-methylethyl)benzenesulfonamide

Product 1

HCID 44125257HCID 44125257, compoundYield 65%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A glass microwave reaction vessel was charged with a mixture of N-(5-bromo-2-chloropyridin-3-yl)-4-(2-hydroxypropan-2-yl)benzenesulfonamide from Step 2 (250 mg, 616 μmol), N-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide from Step 3 (223 mg, 739 μmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride (32 mg, 43 μmol, Strem Chemical, Inc., Newburyport, Mass.), sodium carbonate (131 mg, 1.2 mmol), and dioxane (3 mL). Ar was bubbled in for 1 minute, and the vessel was sealed and heated at 90° C. for 12 h. After cooled down to room temperature, the black suspension was filtered through a Celite® (diatomaceous earth) pad, and the filtercake was washed by MeOH-DCM (50%). The filtrate was concentrated in vacuo. Purification by silica gel chromatography (10 to 20% MeOH/CH2Cl2), followed by further purification by preparative HPLC (Phenomenex Synergi 4μ MAX-RP 150×21.2 mm, 40 to 90% CH3CN/H2O, 0.1% TFA, over 10 min) (Phenomenex, Torrance, Calif.) provided N-(6-(6-chloro-5-(4-(2-hydroxypropan-2-yl)phenylsulfonamido)pyridin-3-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide (20 mg, 65% yield) as a yellow solid. MS (ESI positive ion) m/z: 501 (M+1). 1H NMR (400 MHz, MeOH-d6): δ ppm 1.51 (s, 6H), 2.22 (s, 3H), 7.66 (d, J=8.53 Hz, 2H), 7.71 (d, J=9.54 Hz, 1H), 7.78 (d, J=9.03 Hz, 2H), 7.98 (d, J=9.54 Hz, 1H), 8.43 (s, 1H), 8.56 (d, J=2.01 Hz, 1H), 8.78 (d, J=2.51 Hz, 1H).

Workup

  1. customA glass microwave reaction vessel
  2. customAr was bubbled in for 1 minute
  3. customthe vessel was sealed
  4. temperatureAfter cooled down to room temperature
  5. filtrationthe black suspension was filtered through a Celite® (diatomaceous earth) pad
  6. washthe filtercake was washed by MeOH-DCM (50%)
  7. concentrationThe filtrate was concentrated in vacuo
  8. customPurification by silica gel chromatography (10 to 20% MeOH/CH2Cl2)
  9. customfollowed by further purification by preparative HPLC (Phenomenex Synergi 4μ MAX-RP 150×21.2 mm, 40 to 90% CH3CN/H2O, 0.1% TFA, over 10 min) (Phenomenex, Torrance, Calif.)

Sources & evidence

ORD record
ord-9bfc5251775c40f2a2931db97c7ab9dd
Source dataset
uspto-grants-2010_10
Patent number
US07820665B2

Reaction notes

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