Trifluoroacetic acid methylene chloride → phenyl(1H-pyrrolo[2,3-c]pyridin-2-yl)methanone O-[2-(methylamino)ethyl]oxime dihydrochloride

HRID 1821901ノート

反応式

HRID 1821901 の反応式
[CH3:1][N:2]([CH2:10][CH2:11][O:12][N:13]=[C:14]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:15]1[NH:23][C:18]2=[CH:19][N:20]=[CH:21][CH:22]=[C:17]2[CH:16]=1)C(=O)OC(C)(C)C.FC(F)(F)C(O)=O.C(Cl)[Cl:38]>>[ClH:38].[ClH:38].[CH3:1][NH:2][CH2:10][CH2:11][O:12][N:13]=[C:14]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:15]1[NH:23][C:18]2=[CH:19][N:20]=[CH:21][CH:22]=[C:17]2[CH:16]=1

参加物

3

反応物 2

HCID 21863450Trifluoroacetic acid methylene chlorideHCID 136386514tert-butyl methyl[2-[[[phenyl(1H-pyrrolo[2,3-c]pyridin-2-yl)methylene]amino]oxy]ethyl]carbamate

生成物 1

HCID 136365996phenyl(1H-pyrrolo[2,3-c]pyridin-2-yl)methanone O-[2-(methylamino)ethyl]oxime dihydrochloride収率 51%

実験手順

tert-Butyl methyl[2-[[[phenyl (1H-pyrrolo[2,3-c]pyridin-2-yl)methylene]amino]oxy]ethyl]carbamate (Example 128) (100 mg, 0.25 mmol) in trifluoroacetic acid/CH2Cl2 (2:1, 5 mL) was stirred at ambient temperature. After 5 h, the reaction mixture was concentrated under reduced pressure. The residue was diluted with CH2Cl2 (35 mL) and washed with saturated NaHCO3 (20 mL) and saturated NaCl (20 mL), dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 89:10:1 CH2Cl2/MeOH/NH4OH). The obtained product was dissolved in EtOAc, an excess of 1 N HCl in Et2O was added and the mixture was concentrated under reduced pressure. The resulting solid was triturated with EtOAc and collected by vacuum filtration to give phenyl(1H-pyrrolo[2,3-c]pyridin-2-yl)methanone O-[2-(methylamino)ethyl]oxime dihydrochloride (46.8 mg, 51%) as an off-white solid (geometry of the oxime double bond undefined): 1H NMR (500 MHz, DMSO-d6) δ 2.63 (3H, s), 3.39 (2H, br s), 4.59 (2H, t, J=4.5 Hz), 6.96 (1H, s), 7.50-7.61 (5H, m), 8.14 (1H, d, J=6.3 Hz), 8.34 (1H, d, J=6.3 Hz), 9.31-9.35 (3H, m), 13.56 (1H, s), 15.28 (1H, br s); ESI MS m/z 295 [C17H18N4O+H]+; HPLC (Method A) 96.6% (AUC), tR=13.5 min.

後処理

  1. concentrationthe reaction mixture was concentrated under reduced pressure
  2. additionThe residue was diluted with CH2Cl2 (35 mL)
  3. washwashed with saturated NaHCO3 (20 mL) and saturated NaCl (20 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by column chromatography (silica gel, 89:10:1 CH2Cl2/MeOH/NH4OH)
  7. dissolutionThe obtained product was dissolved in EtOAc
  8. additionan excess of 1 N HCl in Et2O was added
  9. concentrationthe mixture was concentrated under reduced pressure
  10. customThe resulting solid was triturated with EtOAc
  11. filtrationcollected by vacuum filtration

出典と根拠

ORDレコード
ord-b0b11ecb875a44d3b02431ad9bd68f04
出典データセット
uspto-grants-2009_10
特許番号
US07608627B2

反応ノート

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