HCID 58266297, compound → HCID 58266798, compound

HRID 1888590Notes

Reaction equation

HRID 1888590 reaction equation
[Br:1][C:2]1[N:10]=[CH:9][C:8]2[NH:7][C:6]3[N:11]=[CH:12][C:13](I)=[CH:14][C:5]=3[C:4]=2[CH:3]=1.CC1(C)C(C)(C)OB([C:24]2[CH:40]=[CH:39][C:27]([CH2:28][N:29]3[CH2:34][CH2:33][CH:32]([C:35]([F:38])([F:37])[F:36])[CH2:31][CH2:30]3)=[CH:26][CH:25]=2)O1>C(=O)([O-])[O-].[Na+].[Na+]>[Br:1][C:2]1[N:10]=[CH:9][C:8]2[NH:7][C:6]3[N:11]=[CH:12][C:13]([C:24]4[CH:25]=[CH:26][C:27]([CH2:28][N:29]5[CH2:30][CH2:31][CH:32]([C:35]([F:38])([F:36])[F:37])[CH2:33][CH2:34]5)=[CH:39][CH:40]=4)=[CH:14][C:5]=3[C:4]=2[CH:3]=1

Participants

4

Reactant 2

HCID 58266297HCID 58266297, compoundHCID 58266428HCID 58266428, compound

Product 1

HCID 58266798HCID 58266798, compoundYield 7%

Reagents, catalysts & solvents 1

HCID 10340Sodium CarbonateSolvent

Conditions

Temperature
85 °C

Procedure

A degassed mixture of 6-bromo-3-iodo-9H-dipyrido[2,3-b;4′,3′-d]pyrrole (0.64 g, 1.7 mmol), 1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl]-4-trifluoromethyl piperidine (1.14 g, 3.1 mmol) and 1,1′-[bis(diphenyl phosphino)ferrocene]dichloropalladium(II) (0.21 g, 0.26 mmol) in 2-methyl-THF (26 mL) and saturated aqueous sodium carbonate solution (12 mL) was heated at 85° C. for 16 h. The cooled reaction mixture was filtered through celite and partitioned between DCM and water and the phases were separated. The organic phase was dried over sodium sulfate, filtered and evaporated then the residue was purified by flash chromatography (silica, 40 g column, ISCO, 0-15% methanol in DCM). Trituration of the resultant residue with acetonitrile afforded the title compound as a tan solid (57 mg, 7%). 1H NMR (CD3OD, 300 MHz): 8.84 (d, J=2.2 Hz, 1H), 8.70-8.67 (m, 2H), 8.27 (d, J=1.0 Hz, 1H), 7.67 (d, J=8.0 Hz, 2H), 7.49 (d, J=8.0 Hz, 2H), 3.63 (s, 2H), 3.11-3.02 (m, 2H), 2.14-2.02 (m, 3H), 1.94-1.84 (m, 2H), 1.76-1.59 (m, 2H. LCMS (Method B): RT=2.55 min, M+H+=489.

Workup

  1. customThe cooled reaction mixture
  2. filtrationwas filtered through celite
  3. custompartitioned between DCM and water
  4. customthe phases were separated
  5. dry with materialThe organic phase was dried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customthe residue was purified by flash chromatography (silica, 40 g column, ISCO, 0-15% methanol in DCM)

Sources & evidence

ORD record
ord-7777948663444ccebb5d12db534e6ee0
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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