Potassium bis(trimethylsilyl)amide → 5-[5-(3,4-dimethoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-pyridin-2-ylamine

HRID 729847

反応式

HRID 729847 の反応式
[CH3:1][Si]([N-][Si](C)(C)C)(C)C.[K+].[NH2:11][C:12]1[C:17]([C:18]([C:20]2[CH:21]=[N:22][C:23]([NH2:26])=[CH:24][CH:25]=2)=O)=[CH:16][C:15]([C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[C:29]([O:35][CH3:36])[CH:28]=2)=[CH:14][N:13]=1>C1COCC1>[CH3:36][O:35][C:29]1[CH:28]=[C:27]([C:15]2[CH:16]=[C:17]3[C:18]([C:20]4[CH:25]=[CH:24][C:23]([NH2:26])=[N:22][CH:21]=4)=[CH:1][NH:11][C:12]3=[N:13][CH:14]=2)[CH:32]=[CH:31][C:30]=1[O:33][CH3:34]

参加物

4

反応物 2

HCID 3251421Potassium bis(trimethylsilyl)amideHCID 59699897[2-Amino-5-(3,4-dimethoxy-phenyl)-pyridin-3-yl]-(6-amino-pyridin-3-yl)-methanone

生成物 1

HCID 160391495-[5-(3,4-dimethoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-pyridin-2-ylamine収率 29%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a suspension of(methoxymethyl)triphenylphosphonium chloride (166 mg, 0.485 mmol) in THF (1 ml) at 0° C. under nitrogen was added potassium bis(trimethylsilyl)amide (97 mg, 0.485 mmol). The mixture was stirred at room temperature for 30 min, then it was added to [2-amino-5-(3,4-dimethoxy-phenyl)-pyridin-3-yl]-(6-amino-pyridin-3-yl)-methanone (34 mg, 0.097 mmol) in one portion. The reaction mixture was stirred for 2 hours, then quenched with wet methanol and concentrated in vacuo. The crude was diluted with 2 ml of 1,4-dioxane and treated with 0.1 ml of aqueous 70% perchloric acid. The mixture was stirred at 80° C. for 19 hours, diluted with THF/methanol (1:1), and treated with 2.0 g of PS-trisamine (Argonaut Technologies, 4 equivalents per equivalent of acid used) for 30 minutes. The resin was filtered off and washed with THF/MeOH (1:1). Purification was accomplished by flash chromotography on silica gel with a gradient of methanol/dichloromethane afforded 5-[5-(3,4-dimethoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-pyridin-2-ylamine as a yellow solid (9.7 mg, 29% yield). 1H NMR (DMSO-d6): δ 11.8 (s, 1H), 8.51 (d, J=2.0 Hz, 1H), 8.31 (d, J=2.0 Hz, 1H), 8.25 (d, J=2.0 Hz, 1H), 7.77 (dd, J=2.0, 10.0 Hz, 1H), 7.70 (d, J=2.5 Hz, 1H), 7.28 (d, J=2.0 Hz, 1H), 7.24 (dd, J=2.0, 7.5 Hz, 1H), 7.04 (d, J=8.5 Hz, 1H), 6.55 (d, J=8.5 Hz, 1H), 5.90 (broad s, 2H), 3.86 (s, 3H), 3.79 (s, 3H). HPLC/MS m/z: 347.1 [MH]+.

後処理

  1. stirringThe reaction mixture was stirred for 2 hours
  2. customquenched with wet methanol
  3. concentrationconcentrated in vacuo
  4. additionThe crude was diluted with 2 ml of 1,4-dioxane
  5. additiontreated with 0.1 ml of aqueous 70% perchloric acid
  6. stirringThe mixture was stirred at 80° C. for 19 hours
  7. additiondiluted with THF/methanol (1:1)
  8. additiontreated with 2.0 g of PS-trisamine (Argonaut Technologies, 4 equivalents per equivalent of acid used) for 30 minutes
  9. filtrationThe resin was filtered off
  10. washwashed with THF/MeOH (1:1)
  11. customPurification

出典と根拠

ORDレコード
ord-76c5e8dc7a894a73903d33fe6671d3ac
出典データセット
uspto-grants-2009_09
特許番号
US07582637B2

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