Water → [2-Methoxy-4-(4-methyl-piperazin-1-yl)-phenyl]-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-amine

HRID 1261878Notes

Reaction equation

HRID 1261878 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O1CCOCC1.Br[C:27]1[N:35]2[C:30]([CH:31]=[N:32][C:33]([NH:36][C:37]3[CH:42]=[CH:41][C:40]([N:43]4[CH2:48][CH2:47][N:46]([CH3:49])[CH2:45][CH2:44]4)=[CH:39][C:38]=3[O:50][CH3:51])=[N:34]2)=[CH:29][CH:28]=1.[CH3:52][O:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][C:55]=1B(O)O.CN(C)C=O.C(=O)([O-])[O-].[Na+].[Na+].O>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:51][O:50][C:38]1[CH:39]=[C:40]([N:43]2[CH2:44][CH2:45][N:46]([CH3:49])[CH2:47][CH2:48]2)[CH:41]=[CH:42][C:37]=1[NH:36][C:33]1[N:32]=[CH:31][C:30]2=[CH:29][CH:28]=[C:27]([C:55]3[CH:56]=[CH:57][CH:58]=[CH:59][C:54]=3[O:53][CH3:52])[N:35]2[N:34]=1

Participants

9

Reactant 7

HCID 962WaterHCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 312751,4-DioxaneHCID 27339582-Methoxyphenylboronic acidHCID 66710919(7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-[2-methoxy-4-(4-methyl-piperazin-1-yl)-phenyl]-amine

Product 1

HCID 54577897[2-Methoxy-4-(4-methyl-piperazin-1-yl)-phenyl]-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-amine

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
80 °C

Procedure

Into a 30 mL vial, Palladium Acetate (0.010 g, 0.000046 mol) and Triphenylphosphine (0.030 g, 0.00011 mol) were added and purged under an atmosphere of Nitrogen for 5 minutes 1,4-Dioxane (1.00 mL, 0.0128 mol) was added and stirred for 10 minutes. (7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-[2-methoxy-4-(4-methyl-piperazin-1-yl)-phenyl]-amine (0.0952 g, 0.000228 mol), 2-methoxybenzeneboronic acid (0.0694 g, 0.000456 mol), N,N-Dimethylformamide (2.20 mL, 0.0284 mol) and 1.50 M of Sodium carbonate in Water (1.00 mL, 0.00150 mol) were added, respectively. The reaction mixture was heated at 80° C. overnight. The solvent was removed under vacuum. The solid was washed with DCM. The organic was removed under vacuum. The reaction was purified via ISCO column chromatography with DCM and methanol as eluant (0 to 10% methanol). The collected fraction afforded a solid. The solid was washed with 10% Et2O/hexane to give [2-Methoxy-4-(4-methyl-piperazin-1-yl)-phenyl]-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-amine a yellow solid (38 mg, 37%). LCMS (E/I+) 445.19 (M+H). NMR 1H (DSMO-d6)-8.88 (s, 1H), 7.83 (t, 2H, J=8.76 Hz), 7.48 (s, 1H), 7.43 (t, 1H, J=7.16 Hz), 7.19 (d, 1H, J=8.36 Hz), 7.08 (t, 1H, J=7.52 Hz), 6.94 (d, 1H, J=4.68 Hz), 6.90 (d, 1H, J=4.60 Hz), 6.63 (s, 1H), 6.35 (d, 1H, J=9.04 Hz), 3.84 (s, 3H), 3.78 (s, 3H), 3.05-3.16 (bm, 4H), 2.46 (bs, 4H), 2.23 (s, 3H).

Workup

  1. additionwas added
  2. customThe solvent was removed under vacuum
  3. washThe solid was washed with DCM
  4. customThe organic was removed under vacuum
  5. customThe reaction was purified via ISCO column chromatography with DCM and methanol as eluant (0 to 10% methanol)
  6. customThe collected fraction afforded a solid
  7. washThe solid was washed with 10% Et2O/hexane

Sources & evidence

ORD record
ord-e5f73dfa67be4bfc9f8f776b4d6a6372
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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