Pyridine → N-(5-((2-chloropyridin-4-yl)oxy)-6-methylpyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide

HRID 2278969ノート

反応式

HRID 2278969 の反応式
[C:1](Cl)(Cl)=[O:2].[O:5]1[CH2:10][CH2:9][CH:8]([N:11]2[CH2:15][CH2:14][NH:13][C:12]2=[O:16])[CH2:7][CH2:6]1.N1C=CC=CC=1.[Cl:23][C:24]1[CH:29]=[C:28]([O:30][C:31]2[CH:32]=[CH:33][C:34]([NH2:38])=[N:35][C:36]=2[CH3:37])[CH:27]=[CH:26][N:25]=1>C(Cl)Cl>[Cl:23][C:24]1[CH:29]=[C:28]([O:30][C:31]2[CH:32]=[CH:33][C:34]([NH:38][C:1]([N:13]3[CH2:14][CH2:15][N:11]([CH:8]4[CH2:7][CH2:6][O:5][CH2:10][CH2:9]4)[C:12]3=[O:16])=[O:2])=[N:35][C:36]=2[CH3:37])[CH:27]=[CH:26][N:25]=1

参加物

6

反応物 4

HCID 1049PyridineHCID 6371PhosgeneHCID 904029725-((2-Chloropyridin-4-yl)oxy)-6-methylpyridin-2-amineHCID 904259751-(Oxan-4-yl)imidazolidin-2-one

生成物 1

HCID 90426065N-(5-((2-chloropyridin-4-yl)oxy)-6-methylpyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide収率 52.4%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

Phosgene (20% in toluene, 2.62 g, 5.3 mmol) was treated with a solution of Example B1 (0.27 g, 1.59 mmol) and pyridine (0.43 mL, 5.3 mmol) in DCM (5 mL), stirred for 15 min, then concentrated to dryness. The residue was dissolved in DCM (5 mL), treated with a solution of Example A7 (0.25 g, 1.06 mmol) and TEA (0.74 mL, 5.3 mmol) in DCM (5 mL) and stirred at RT for 1 h. The mixture was treated with satd. NaHCO3, extracted with EtOAc (2×) and the combined organics were washed with brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (EtOAc/Hex) to afford N-(5-((2-chloropyridin-4-yl)oxy)-6-methylpyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (0.24 g, 52%). 1H NMR (400 MHz, DMSO-d6): δ 10.91 (s, 1 H), 8.27 (d, J=5.8 Hz, 1 H), 7.90 (d, J=8.8 Hz, 1 H), 7.65 (d, J=8.8 Hz, 1 H), 7.02 (d, J=2.3 Hz, 1 H), 6.92 (dd, J=5.8, 2.3 Hz, 1 H), 3.94-3.84 (m, 5 H), 3.48-3.35 (m, 4 H), 2.21 (s, 3 H), 1.74-1.66 (m, 2 H), 1.60 (d, J=12.5 Hz, 2 H); MS (ESI) m/z: 432.1 (M+H+).

後処理

  1. concentrationconcentrated to dryness
  2. dissolutionThe residue was dissolved in DCM (5 mL)
  3. stirringstirred at RT for 1 h
  4. additionThe mixture was treated with satd
  5. extractionNaHCO3, extracted with EtOAc (2×)
  6. washthe combined organics were washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated to dryness
  9. custompurified via silica gel chromatography (EtOAc/Hex)

出典と根拠

ORDレコード
ord-231a34df98fa43c48509a972f93b54f0
出典データセット
uspto-grants-2015_09
特許番号
US09133183B2

反応ノート

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