HCID 58266297, compound → HCID 58266391, compound

HRID 1506055Notes

Reaction equation

HRID 1506055 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.[CH3:16][O:17][CH:18]1[CH2:23][CH2:22][N:21]([CH2:24][C:25]2[CH:30]=[CH:29][C:28](B3OC(C)(C)C(C)(C)O3)=[CH:27][CH:26]=2)[CH2:20][CH2:19]1>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:28]4[CH:27]=[CH:26][C:25]([CH2:24][N:21]5[CH2:20][CH2:19][CH:18]([O:17][CH3:16])[CH2:23][CH2:22]5)=[CH:30][CH:29]=4)=[CH:14][C:5]=3[C:4]=2[CH:3]=1

Participants

4

Reactant 2

HCID 58266297HCID 58266297, compoundHCID 58266440HCID 58266440, compound

Product 1

HCID 58266391HCID 58266391, compoundYield 28.1%

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 (0.50 g, 1.3 mmol), 4-methoxy-1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl]-piperidine (0.80 g, 2.4 mmol) and 1,1′-[bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.16 g, 0.2 mmol) in 2-methyl THF (20 mL) and saturated aqueous sodium carbonate (10 mL) was heated at 85° C. for 3 h. The material was partitioned between DCM, water and methanol and the phases were separated. The organic phase was separated, dried over sodium sulfate, filtered and evaporated to afford a residue which was purified by flash chromatography (silica, 50 g column, Biotage, 0-10% methanol in DCM). The resultant material was triturated with methanol to afford the title compound as a tan solid (0.165 g, 28%). 1H NMR (CDCl3 plus CD3OD, 300 MHz): 8.84 (d, J=2.2 Hz, 1H), 8.73 (d, J=2.2 Hz, 1H), 8.69 (d, J=0.9 Hz, 1H), 8.30 (d, J=1.0 Hz, 1H), 7.68 (d, J=8.0 Hz, 2H), 7.49 (d, J=8.0 Hz, 2H), 3.63 (s, H), 2.89-2.76 (m, 2H), 2.37-2.22 (m, 2H), 2.02-1.89 (m, 2H), 1.73-1.56 (m, 2H). LCMS (Method G): RT=3.30 min, M+H+=451.

Workup

  1. customThe material was partitioned between DCM, water and methanol
  2. customthe phases were separated
  3. customThe organic phase was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customto afford a residue which
  8. customwas purified by flash chromatography (silica, 50 g column, Biotage, 0-10% methanol in DCM)
  9. customThe resultant material was triturated with methanol

Sources & evidence

ORD record
ord-9163d4a7072d41a8a2fe56b1bc576388
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

Loading…