HCID 58266297, compound → HCID 58266391, compound

HRID 1888592Notes

Reaction equation

HRID 1888592 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-68913b4af78b402e8103dd5ecdbbb115
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

Loading…