Potassium Carbonate → HCID 118502145, compound

HRID 1486958Notes

Reaction equation

HRID 1486958 reaction equation
[F:1][C:2]1[N:7]=[CH:6][C:5](B(O)O)=[CH:4][CH:3]=1.Br[C:12]1[C:21]([F:22])=[CH:20][C:19]2[N:18]=[CH:17][C:16]3[N:23]([CH3:33])[C:24](=[O:32])[N:25]([CH:26]4[CH2:31][CH2:30][O:29][CH2:28][CH2:27]4)[C:15]=3[C:14]=2[CH:13]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.CC(P(C(C)(C)C)C1[CH-]C=CC=1)(C)C.CC(P(C(C)(C)C)C1[CH-]C=CC=1)(C)C.[Cl-].[Cl-].[Fe+2].[Pd+2]>[F:22][C:21]1[C:12]([C:5]2[CH:6]=[N:7][C:2]([F:1])=[CH:3][CH:4]=2)=[CH:13][C:14]2[C:15]3[N:25]([CH:26]4[CH2:27][CH2:28][O:29][CH2:30][CH2:31]4)[C:24](=[O:32])[N:23]([CH3:33])[C:16]=3[CH:17]=[N:18][C:19]=2[CH:20]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 2783397(6-Fluoropyridin-3-yl)boronic acidHCID 118498872HCID 118498872, compound

Product 1

HCID 118502145HCID 118502145, compoundYield 88.2%

Reagents, catalysts & solvents 3

HCID 53384307Dichloro[1,1'-bis(di-tert-butylphosphino)ferrocene]palladium(II)CatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

(6-Fluoropyridin-3-yl)boronic acid (0.445 g, 3.16 mmol), 8-bromo-7-fluoro-3-methyl-1-(oxan-4-yl)imidazo[5,4-c]quinolin-2-one (1 g, 2.63 mmol) and 2M K2CO3 (3.95 mL, 7.89 mmol) were suspended in dioxane (3 mL) and water (0.75 mL). The reaction was degassed with nitrogen and then dichloro[1,1′-bis(di-tert-butylphosphino)ferrocene]palladium(II) (0.086 g, 0.13 mmol) was added and the reaction heated to 80° C. for 1 h in the microwave reactor. The mixture was allowed to cool, diluted with water then extracted with DCM (2×100 mL). The combined organic phases were separated and concentrated in vacuo. The crude product was purified by FCC, elution gradient 0 to 10% methanolic ammonia in DCM, to afford the desired material as a beige solid (0.92 g, 88%). NMR Spectrum: 1H NMR (500 MHz, DMSO-d6) δ 1.90 (2H, dd), 2.69 (2H, qt), 3.49-3.59 (5H, m), 3.97-4.06 (2H, m), 5.08 (1H, tt), 7.38-7.45 (1H, m), 7.96 (1H, d), 8.34-8.42 (2H, m), 8.61-8.65 (1H, m), 8.95 (1H, s). Mass Spectrum: m/z (ES+)[M+H]+=397

Workup

  1. customThe reaction was degassed with nitrogen
  2. temperatureto cool
  3. extractionthen extracted with DCM (2×100 mL)
  4. customThe combined organic phases were separated
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by FCC, elution gradient 0 to 10% methanolic ammonia in DCM

Sources & evidence

ORD record
ord-3063c62f0cec4a99978556e8fbec5182
Source dataset
uspto-grants-2016_08
Patent number
US09428503B2

Reaction notes

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