Water → HCID 46851380, compound

HRID 1262296Notes

Reaction equation

HRID 1262296 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Br[C:21]1[N:29]2[C:24]([CH:25]=[N:26][C:27]([NH:30][C:31]3[CH:36]=[CH:35][C:34]([N:37]4[CH2:42][CH2:41][N:40]([CH3:43])[CH2:39][CH2:38]4)=[CH:33][CH:32]=3)=[N:28]2)=[CH:23][CH:22]=1.[CH:44]([C:46]1[O:47][C:48](B(O)O)=[CH:49][CH:50]=1)=[O:45].C(=O)([O-])[O-].[Na+].[Na+].O>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C)C=O.O1CCOCC1>[CH3:43][N:40]1[CH2:41][CH2:42][N:37]([C:34]2[CH:33]=[CH:32][C:31]([NH:30][C:27]3[N:26]=[CH:25][C:24]4=[CH:23][CH:22]=[C:21]([C:48]5[O:47][C:46]([CH:44]=[O:45])=[CH:50][CH:49]=5)[N:29]4[N:28]=3)=[CH:36][CH:35]=2)[CH2:38][CH2:39]1

Participants

9

Reactant 5

HCID 962WaterHCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 27343555-Formylfuran-2-boronic acidHCID 66711200(7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine

Product 1

HCID 46851380HCID 46851380, compoundYield 33.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Procedure

Into a 8-dram vial, Palladium Acetate (0.00988 g, 0.0440 mmol), Triphenylphosphine (0.0338 g, 0.129 mmol) and 1,4-Dioxane (2 mL) were added and stirred at room temperature for 10 minutes. (7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine (0.320 g, 0.826 mmol), 2-Formylfuran-5-boronic acid (0.2312 g, 1.652 mmol), N,N-Dimethylformamide (2 mL) and 1.50 M of Sodium carbonate in Water (6 mL, 10 mmol) were added. The reaction mixture was heated at 90° C. overnight. The reaction was cooled to room temperature. Solvent was removed under vacuum to give a yellow solid. The resulting solid was partitioned with water and DCM. The organic was separated, washed with Brine and dried over Na2SO4. The solid was filtered and washed with DCM. The solvent was removed under vacuum. The reaction mixture was purified via ISCO column chromatography with DCM and methanol as eluant (5 to 25% methanol). The collected fractions afforded 5-{2-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-7-yl}-furan-2-carbaldehyde as a yellow solid (110 mg, 33%). LCMS (E/I+) 403.19 (M+H). NMR 1H (DMSO-d6)-963 (s, 1H), 9.40 (s, 1H), 9.04 (s, 1H), 7.78 (d, 1H, J=3.07 Hz), 7.62 (d, 2H, J=9.05 Hz), 7.45 (d, 1H, J=3.77 Hz), 7.21 (d, 1H, J=4.90 Hz), 7.01 (d, 2H, J=9.05 Hz), 6.97 (d, 1H, J=4.90 Hz), 3.11 (t, 4H, J=4.91 Hz), 2.47 (t, 4H, J=4.91 Hz), 2.23 (s, 3H).

Workup

  1. temperatureThe reaction mixture was heated at 90° C. overnight
  2. temperatureThe reaction was cooled to room temperature
  3. customSolvent was removed under vacuum
  4. customto give a yellow solid
  5. customThe resulting solid was partitioned with water and DCM
  6. customThe organic was separated
  7. washwashed with Brine
  8. dry with materialdried over Na2SO4
  9. filtrationThe solid was filtered
  10. washwashed with DCM
  11. customThe solvent was removed under vacuum
  12. customThe reaction mixture was purified via ISCO column chromatography with DCM and methanol as eluant (5 to 25% methanol)

Sources & evidence

ORD record
ord-bedd96f3a00e4df49a5c44042e7df124
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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