Potassium Carbonate → 5-(2-benzyl-2H-indazol-6-yl)-7-[4-(4-propylpiperazin-1-yl)phenyl]pyrrolo[2,1-f][1,2,4]triazin-4-amine

HRID 1972770ノート

反応式

HRID 1972770 の反応式
[CH2:1]([N:8]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([C:17]3[CH:18]=[C:19]([C:27]4[CH:32]=[CH:31][C:30]([N:33]5[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]5)=[CH:29][CH:28]=4)[N:20]4[C:25]=3[C:24]([NH2:26])=[N:23][CH:22]=[N:21]4)[CH:13]=[CH:14]2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.I[CH2:40][CH2:41][CH3:42].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH2:1]([N:8]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([C:17]3[CH:18]=[C:19]([C:27]4[CH:32]=[CH:31][C:30]([N:33]5[CH2:38][CH2:37][N:36]([CH2:40][CH2:41][CH3:42])[CH2:35][CH2:34]5)=[CH:29][CH:28]=4)[N:20]4[C:25]=3[C:24]([NH2:26])=[N:23][CH:22]=[N:21]4)[CH:13]=[CH:14]2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参加物

5

反応物 3

HCID 11430Potassium CarbonateHCID 336431-IodopropaneHCID 585294985-(2-benzyl-2H-indazol-6-yl)-7-(4-piperazin-1-ylphenyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine

生成物 1

HCID 585294225-(2-benzyl-2H-indazol-6-yl)-7-[4-(4-propylpiperazin-1-yl)phenyl]pyrrolo[2,1-f][1,2,4]triazin-4-amine収率 25.8%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
50 °C

実験手順

To a solution of 5-(2-benzyl-2H-indazol-6-yl)-7-(4-piperazin-1-ylphenyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine (75 mg, 0.15 mmol) and 1-iodopropane (31 mg, 0.18 mmol) in DMF (2 mL) was added potassium carbonate (37 mg, 0.27 mmol). The reaction was heated (50° C.) for 17 h. The reaction was cooled to rt and was partitioned between ethyl acetate (25 mL) and H2O (25 mL). The layers were separated and the organic was washed with brine, dried (Na2SO4) and concentrated. The residue was purified by preparative HPLC using a gradient elution from 15% to 50% acetonitrile in water followed by trituration with Et2O to obtain 21 mg (25%) of the desired product. 1H NMR (300 MHz, DMSO-d6) δ 8.55 (s, 1 H), 7.97-7.91 (m, 3 H), 7.81 (d, 1 H), 7.65 (s, 1 H), 7.37-7.26 (m, 5H), 7.19 (d, 1 H), 7.04-6.96 (m, 3 H), 5.66 (s, 2 H), 325-3.15 (m, 4 H), 2.51-2.48 (m, 4 H), 2.32-2.24 (m, 2 H), 1.53-1.42 (m, 2 H), 0.88 (t, 3 H), 2.89 (s, 4 H); ES-MS m/z 543.4 [M+H]+, HPLC RT (min) 2.40.

後処理

  1. temperatureThe reaction was cooled to rt
  2. customwas partitioned between ethyl acetate (25 mL) and H2O (25 mL)
  3. customThe layers were separated
  4. washthe organic was washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe residue was purified by preparative HPLC
  8. washa gradient elution from 15% to 50% acetonitrile in water

出典と根拠

ORDレコード
ord-bdad6782e96f4c138abe9d13c0fd613b
出典データセット
uspto-grants-2013_04
特許番号
US08431695B2

反応ノート

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