Dichloromethane → HCID 46913620, compound

HRID 1025397Notes

Reaction equation

HRID 1025397 reaction equation
Br[C:2]1[N:6]2[N:7]=[C:8]([Cl:11])[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.[Cl:12][C:13]1[C:18]([NH:19][S:20]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)(=[O:22])=[O:21])=[CH:17][C:16](B2OC(C)(C)C(C)(C)O2)=[CH:15][N:14]=1.ClCCl.C(=O)([O-])[O-].[Na+].[Na+]>Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O.O1CCOCC1>[Cl:12][C:13]1[C:18]([NH:19][S:20]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)(=[O:22])=[O:21])=[CH:17][C:16]([C:2]2[N:6]3[N:7]=[C:8]([Cl:11])[CH:9]=[CH:10][C:5]3=[N:4][CH:3]=2)=[CH:15][N:14]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 128723233-Bromo-6-chloroimidazo(1,2-b)pyridazineHCID 53363355n-[2-Chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl]-4-fluorobenzene-1-sulfonamide

Product 1

HCID 46913620HCID 46913620, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a 10-mL, reaction vial was added 3-bromo-6-chloroimidazo[1,2-b]pyridazine (0.100 g, 0.43 mmol, Combi-Blocks, San Diego, Calif.), N-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide (0.213 g, 0.52 mmol), [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium, complex with dichloromethane (24 mg, 0.032 mmol), sodium carbonate (0.137 g, 1.29 mmol), dioxane (2 mL) and water (1 mL). The vial was sealed and purged with nitrogen for several minutes. The reaction mixture was stirred at 100° C. for 1 h and then allowed to cool to room temperature. The organic phase was taken and the solvents eliminated under vacuum. The crude reaction mixture was purified first by silica gel chromatography (1 to 3% MeOH/CH2Cl2) followed by preparative HPLC (30-90% ACN 0.1% TFA/water 0.1% TFA) and free based by treatment with a sat aqueous solution of sodium bicarbonate and extraction with dichloromethane (3×). The combined organics were dried over Na2SO4, filtered and the solvents were eliminated under vacuum. The title compound was obtained as a white solid. MS (ESI positive ion) m/z: 438.0 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 7.43 (t, J=8.7 Hz, 2H) 7.52 (d, J=9.6 Hz, 1H) 7.86-7.94 (m, 2H) 8.36 (d, J=9.4 Hz, 1H) 8.49 (s, 1H) 8.57 (d, J=1.8 Hz, 1H) 8.89 (s, 1H) 10.52 (s, 1H).

Workup

  1. customTo a 10-mL, reaction
  2. customThe vial was sealed
  3. custompurged with nitrogen for several minutes
  4. temperatureto cool to room temperature
  5. customThe crude reaction mixture
  6. customwas purified first by silica gel chromatography (1 to 3% MeOH/CH2Cl2)
  7. extractionfree based by treatment with a sat aqueous solution of sodium bicarbonate and extraction with dichloromethane (3×)
  8. dry with materialThe combined organics were dried over Na2SO4
  9. filtrationfiltered

Sources & evidence

ORD record
ord-bd796e84add04cd98a71ba77ba051b2d
Source dataset
uspto-grants-2014_05
Patent number
US08729074B2

Reaction notes

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