Pyridine → N-(6-ethyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide

HRID 2279001ノート

反応式

HRID 2279001 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.[CH2:23]([C:25]1[N:30]=[C:29]([NH2:31])[CH:28]=[CH:27][C:26]=1[O:32][C:33]1[CH:38]=[CH:37][N:36]=[C:35]([C:39]2[CH:40]=[N:41][N:42]([CH3:44])[CH:43]=2)[CH:34]=1)[CH3:24]>C(Cl)Cl.CCOC(C)=O.O>[CH2:23]([C:25]1[N:30]=[C:29]([NH:31][C:1]([N:13]2[CH2:14][CH2:15][N:11]([CH:8]3[CH2:7][CH2:6][O:5][CH2:10][CH2:9]3)[C:12]2=[O:16])=[O:2])[CH:28]=[CH:27][C:26]=1[O:32][C:33]1[CH:38]=[CH:37][N:36]=[C:35]([C:39]2[CH:40]=[N:41][N:42]([CH3:44])[CH:43]=2)[CH:34]=1)[CH3:24]

参加物

8

反応物 4

HCID 1049PyridineHCID 6371PhosgeneHCID 904038036-Ethyl-5-[[2-(1-methyl-1h-pyrazol-4-yl)-4-pyridinyl]oxy]-2-pyridinamineHCID 904259751-(Oxan-4-yl)imidazolidin-2-one

生成物 1

HCID 86268413N-(6-ethyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide収率 60.5%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6344Dichloromethane溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

A solution of phosgene (15% in toluene, 1.440 g, 2.184 mmol) under Ar, was treated with a solution of Example B1 (0.149 g, 0.874 mmol) and pyridine (0.104 g, 1.310 mmol) in DCM (4 mL), stirred for 15 min, then concentrated to dryness. The residue was treated with a solution of Example A9 (0.129 g, 0.437 mmol) and TEA (0.221 g, 2.184 mmol) in DCM (4 mL), stirred for 0.5 h, then treated with water and EtOAc. The layers were separated, the aqueous layer extracted with additional EtOAc (1×) and the combined organics were washed with brine, dried over Na2SO4, concentrated to dryness and purified via reverse-phase chromatography (MeCN/H2O with 0.1% TFA). The organics were removed under reduced pressure and the aqueous residue was neutralized with satd. NaHCO3 and extracted with EtOAc (2×). The combined organics were washed with brine, dried over Na2SO4 and concentrated to dryness to afford N-(6-ethyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (130 mg, 60%). 1H NMR (400 MHz, DMSO-d6): δ 10.91 (s, 1 H), 8.33 (d, J=5.7 Hz, 1 H), 8.24 (s, 1 H), 7.94 (d, J=0.7 Hz, 1 H), 7.89 (d, J=8.8 Hz, 1 H), 7.59 (d, J=8.8 Hz, 1 H), 7.17 (d, J=2.4 Hz, 1 H), 6.58 (dd, J=5.7, 2.4 Hz, 1 H), 3.90-3.87 (m, 3 H), 3.83 (s, 3 H), 3.81-3.79 (m, 2 H), 3.45 (t, J=8.3 Hz, 2 H), 3.37 (dd, J=12.4, 10.5 Hz, 2 H), 2.56 (q, J=7.5 Hz, 2 H), 1.71 (qd, J=12.2, 4.5 Hz, 2 H), 1.62-1.58 (m, 2 H), 1.10 (t, J=7.5 Hz, 3H); MS (ESI) m/z: 492.3 (M+H+).

後処理

  1. concentrationconcentrated to dryness
  2. stirringstirred for 0.5 h
  3. customThe layers were separated
  4. extractionthe aqueous layer extracted with additional EtOAc (1×)
  5. washthe combined organics were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated to dryness
  8. custompurified via reverse-phase chromatography (MeCN/H2O with 0.1% TFA)
  9. customThe organics were removed under reduced pressure
  10. extractionNaHCO3 and extracted with EtOAc (2×)
  11. washThe combined organics were washed with brine
  12. dry with materialdried over Na2SO4
  13. concentrationconcentrated to dryness

出典と根拠

ORDレコード
ord-518ecaaafa364f33ac9d4ed8d8fd7f6d
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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