Sodium Carbonate → HCID 86716511, compound

HRID 1501339Notes

Reaction equation

HRID 1501339 reaction equation
[C:1]1([C:7]2[N:11]3[N:12]=[C:13](Br)[CH:14]=[C:15](Br)[C:10]3=[N:9][C:8]=2[C:18]2[CH:23]=[CH:22][C:21]([C:24]3([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:27][CH2:26][CH2:25]3)=[CH:20][CH:19]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[F:36][C:37]1[CH:42]=[CH:41][C:40](B(O)O)=[CH:39][CH:38]=1.C(=O)([O-])[O-].[Na+].[Na+]>O.O1CCOCC1.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]>[F:36][C:37]1[CH:42]=[CH:41][C:40]([C:13]2[CH:14]=[C:15]([C:40]3[CH:41]=[CH:42][C:37]([F:36])=[CH:38][CH:39]=3)[C:10]3[N:11]([C:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)=[C:8]([C:18]4[CH:23]=[CH:22][C:21]([C:24]5([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:25][CH2:26][CH2:27]5)=[CH:20][CH:19]=4)[N:9]=3)[N:12]=2)=[CH:39][CH:38]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 86716497HCID 86716497, compound

Product 1

HCID 86716511HCID 86716511, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

A mixture of tert-butyl (1-{4-[3-phenyl-6,8-dibromoimidazo[1,2-b]pyridazin-2-yl]phenyl}cyclobutyl)carbamate that was prepared in a manner analgous to that described for Intermediate Example Int-6 (0.25 g, 0.42 mmol), (4-fluorophenyl)boronic acid (0.12 g, 0.84 mmol, 2.0 equiv.), 1,1′-bis(diphenylphosphino)ferrocenepalladium(II) dichloride (0.034 g, 0.042 mmol, 0.1 equiv.) and sodium carbonate (0.13 g, 1.25 mmol, 3.0 equiv) in a mixture of water (0.6 mL) and dioxane (4.5 mL) was irradiated in a microwave apparatus at 110° C. for 60 min. The resulting reaction mixture was added to water (25 mL). The aqueous mixture was extracted with DCM (3×25 mL). The combined organic phases were washed with an aqueous NaOH solution (2 N), dried (Na2SO4 anh.) and concentrated under reduced pressure to give impure tert-butyl (1-{4-[6,8-bis(4-fluorophenyl)-3-phenylimidazo[1,2-b]pyridazin-2-yl]phenyl}cyclobutyl)carbamate (0.39 g) which was used without further purification:

Workup

  1. customwas prepared in a manner analgous to
  2. customwas irradiated in a microwave apparatus at 110° C. for 60 min
  3. customThe resulting reaction mixture
  4. extractionThe aqueous mixture was extracted with DCM (3×25 mL)
  5. washThe combined organic phases were washed with an aqueous NaOH solution (2 N)
  6. dry with materialdried (Na2SO4 anh.)
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-8b42fb57b3f64765b4fb1450b747591c
Source dataset
uspto-grants-2015_12
Patent number
US09206185B2

Reaction notes

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