HCID 58266297, compound → HCID 58266787, compound

HRID 1506048Notes

Reaction equation

HRID 1506048 reaction equation
[CH3:1][C:2]1([CH3:24])[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][C:12](B3OC(C)(C)C(C)(C)O3)=[CH:11][CH:10]=2)[CH2:4][CH2:3]1.I[C:26]1[CH:39]=[N:38][C:29]2[NH:30][C:31]3[CH:36]=[N:35][C:34]([Br:37])=[CH:33][C:32]=3[C:28]=2[CH:27]=1>[F-].[K+].C(#N)C.C(OCC)(=O)C>[Br:37][C:34]1[N:35]=[CH:36][C:31]2[NH:30][C:29]3[N:38]=[CH:39][C:26]([C:12]4[CH:11]=[CH:10][C:9]([CH2:8][N:5]5[CH2:4][CH2:3][C:2]([CH3:1])([CH3:24])[CH2:7][CH2:6]5)=[CH:14][CH:13]=4)=[CH:27][C:28]=3[C:32]=2[CH:33]=1

Participants

6

Reactant 2

HCID 58266297HCID 58266297, compoundHCID 58266319HCID 58266319, compound

Product 1

HCID 58266787HCID 58266787, compoundYield 33%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolventHCID 522689Potassium FluorideSolvent

Conditions

Temperature
80 °C

Procedure

A degassed mixture of 4,4-dimethyl-1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl]-piperidine (836 mg, 2.5 mmol), 3-iodo-6-bromo-9H-dipyrido[2,3-b;4′,3′-d]pyrrole (500 mg, 1.3 mmol), 1,1′-[bis(diphenylphosphino)ferrocene]dichloropalladium(II) (109 mg, 0.13 mmol) in 1N aqueous potassium fluoride solution (25 mL) and acetonitrile (25 mL) was heated at 80° C. for 18 h. The cooled reaction mixture was diluted with ethyl acetate (100 mL) then washed with water (75 mL). The organic phase was separated, dried over sodium sulfate, filtered and evaporated in vacuo to afford a residue that was purified by flash chromatography (silica, 120 g column, ISCO, 0-15% methanol in DCM) to afford the title compound as an off-white solid (190 mg, 33%). 1H NMR (CDCl3 plus CD3OD, 300 MHz): 8.85 (d, J=2.2 Hz, 1H), 8.76 (d, J=2.2 Hz, 1H), 8.70 (d, J=0.9 Hz, 1H), 8.32 (d, J=0.9 Hz, 1H), 7.73 (d, J=8.0 Hz, 2H), 7.54 (d, J=8.0 Hz, 2H), 3.82 (s, 2H), 2.77-2.63 (m, 4H), 1.52 (t, J=5.6 Hz, 4H), 1.00 (s, 6H).

Workup

  1. customThe cooled reaction mixture
  2. washthen washed with water (75 mL)
  3. customThe organic phase was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customto afford a residue that
  8. customwas purified by flash chromatography (silica, 120 g column, ISCO, 0-15% methanol in DCM)

Sources & evidence

ORD record
ord-a83d9c94eadb48b19d25a418a75e57f8
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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