Ethanol → (7-Pyridin-3-yl-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-amine

HRID 1261963Notes

Reaction equation

HRID 1261963 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O1CCCC1.Br[C:26]1[N:34]2[C:29]([CH:30]=[N:31][C:32]([NH:35]C3C=CC(N4CCC(N5CCN(C)CC5)CC4)=CC=3OC)=[N:33]2)=[CH:28][CH:27]=1.[N:57]1[CH:62]=[CH:61][CH:60]=[C:59](B(O)O)[CH:58]=1.C(=O)([O-])[O-].[Na+].[Na+].O.C(O)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N:57]1[CH:62]=[CH:61][CH:60]=[C:59]([C:26]2[N:34]3[C:29]([CH:30]=[N:31][C:32]([NH2:35])=[N:33]3)=[CH:28][CH:27]=2)[CH:58]=1

Participants

9

Reactant 7

HCID 702EthanolHCID 962WaterHCID 8028TetrahydrofuranHCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 27343783-Pyridinylboronic acidHCID 66711255(7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-{2-methoxy-4-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-phenyl}-amine

Product 1

HCID 86661668(7-Pyridin-3-yl-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-amineYield 133.7%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

Palladium Acetate (0.009 g, 0.00004 mol) and Triphenylphosphine (0.013 g, 0.000050 mol) were dissolved in Tetrahydrofuran (4 mL, 0.05 mol) and the mixture was allowed to stir at room temperature for 10 minutes. (7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-{2-methoxy-4-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-phenyl}-amine (0.10 g, 0.00020 mol) (For preparation see Example 242) was then added and the reaction was again allowed to stir for 10 minutes. 3-Pyridylboronic acid (0.034 g, 0.00028 mol) was added followed by 1 M of Sodium carbonate in Water (0.70 mL, 0.0007 mol) and Ethanol (2 mL, 0.03 mol). The reaction mixture was then heated at 80° C. overnight. The solvent was removed under vacuum. The product was worked up with brine and DCM. Purification by prep plate chromatography gave 2-Methoxy-4-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-phenyl}-(7-pyridin-3-yl-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-amine as a tan solid (0.0565 g, 56%). MP: 68-70° C.; 1H-NMR (DMSO, 400 MHz) δ 9.30 (d, 1H, J=2.16 Hz), 8.95 (s, 1H), 8.56 (d, 1H, J=8.08 Hz), 8.52 (d, 1H, J=4.76 Hz), 7.89 (s, 1H), 7.64 (d, 1H, J=5.97Hz), 7.47 (q, 1H, J=4.76 Hz), 7.29 (d, 1H, J=4.80 Hz), 6.95 (d, 1H, J=4.80 Hz), 6.67 (d, 1H, J=2.36 Hz) 6.51 (q, 1H, J=2.48 Hz), 3.82 (s, 3H), 3.72 (d, 2H, J=12.48 Hz), 2.7 (t, 1H, J=11.44 Hz), 2.33-2.30 (m, 4H, J=10.32 Hz), 1.54 (q, 2H).

Workup

  1. stirringto stir for 10 minutes
  2. temperatureThe reaction mixture was then heated at 80° C. overnight
  3. customThe solvent was removed under vacuum
  4. customPurification by prep plate chromatography

Sources & evidence

ORD record
ord-f7aebd37866a460d9d4f10fe1b7148b4
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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