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

HRID 1261963ノート

反応式

HRID 1261963 の反応式
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

参加物

9

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 167845palladium(II) acetate触媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-f7aebd37866a460d9d4f10fe1b7148b4
出典データセット
uspto-grants-2013_06
特許番号
US08471005B2

反応ノート

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