Pyridine → N-(6-ethyl-5-((6'-methyl-[2,3'-bipyridin]-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide

HRID 2279009ノート

反応式

HRID 2279009 の反応式
[O:1]1[CH2:6][CH2:5][CH:4]([N:7]2[CH2:11][CH2:10][NH:9][C:8]2=[O:12])[CH2:3][CH2:2]1.N1C=CC=CC=1.[C:19](Cl)(Cl)=[O:20].[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][C:42]([CH3:45])=[CH:43][CH:44]=2)[CH:34]=1)[CH3:24]>C(Cl)Cl>[CH2:23]([C:25]1[N:30]=[C:29]([NH:31][C:19]([N:9]2[CH2:10][CH2:11][N:7]([CH:4]3[CH2:3][CH2:2][O:1][CH2:6][CH2:5]3)[C:8]2=[O:12])=[O:20])[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][C:42]([CH3:45])=[CH:43][CH:44]=2)[CH:34]=1)[CH3:24]

参加物

6

反応物 4

HCID 1049Pyridine2 回HCID 6371PhosgeneHCID 904259751-(Oxan-4-yl)imidazolidin-2-oneHCID 904265476-Ethyl-5-((6'-methyl-[2,3'-bipyridin]-4-yl)oxy)pyridin-2-amine

生成物 1

HCID 86269026N-(6-ethyl-5-((6'-methyl-[2,3'-bipyridin]-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide収率 7.2%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

A 0° C. solution of Example B1 (0.19 g, 1.116 mmol) and pyridine (0.26 mL, 3.21 mmol) in DCM (5 mL) was treated drop-wise with phosgene (20% in toluene, 1.4 mL, 2.65 mmol) and warmed to RT over 0.5 h. The mixture was treated slowly with a solution of 6-ethyl-5-((6′-methyl-[2,3′-bipyridin]-4-yl)oxy)pyridin-2-amine (0.16 g, 0.522 mmol) and pyridine (0.16 mL, 1.978 mmol) in DCM (5 mL) and stirred at RT overnight. The mixture was treated with satd. NaHCO3, extracted with EtOAc (4×) and the combined organics were dried over MgSO4, concentrated to dryness, purified via silica gel chromatography (MeOH/DCM), then re-purified via reverse-phase chromatography (MeCN/H2O with 0.1% TFA). The combined fractions were treated with satd. NaHCO3, extracted with DCM (5×) and the combined organics were dried over MgSO4 and concentrated to dryness to afford N-(6-ethyl-5-((6′-methyl-[2,3′-bipyridin]-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (19 mg, 7%). 1H NMR (400 MHz, DMSO-d6): δ 10.93 (s, 1 H), 9.09 (d, J=2.4 Hz, 1 H), 8.52 (d, J=5.7 Hz, 1 H), 8.28 (dd, J=8.1, 2.4 Hz, 1 H), 7.90 (d, J=8.8 Hz, 1 H), 7.64 (d, J=8.8 Hz, 1 H), 7.59 (d, J=2.4 Hz, 1 H), 7.33 (d, J=8.2 Hz, 1H), 6.77 (dd, J=5.7, 2.4 Hz, 1 H), 3.94-3.84 (m, 3 H), 3.83-3.79 (m, 2 H), 3.46 (t, J=8.2 Hz, 2 H), 3.38 (t, J=11.6 Hz, 2 H), 2.58 (q, J=7.5 Hz, 2 H), 2.50 (s, 3 H), 1.72 (dd, J=12.3, 4.5 Hz, 2 H), 1.62 (s, 2 H), 1.12 (t, J=7.5 Hz, 3H); MS (ESI) m/z: 503.3 (M+H+).

後処理

  1. additionThe mixture was treated with satd
  2. extractionNaHCO3, extracted with EtOAc (4×)
  3. dry with materialthe combined organics were dried over MgSO4
  4. concentrationconcentrated to dryness
  5. custompurified via silica gel chromatography (MeOH/DCM)
  6. customre-purified via reverse-phase chromatography (MeCN/H2O with 0.1% TFA)
  7. additionThe combined fractions were treated with satd
  8. extractionNaHCO3, extracted with DCM (5×)
  9. dry with materialthe combined organics were dried over MgSO4
  10. concentrationconcentrated to dryness

出典と根拠

ORDレコード
ord-74742d3d81a3463b9c3438d2de77962d
出典データセット
uspto-grants-2015_09
特許番号
US09133183B2

反応ノート

読み込み中…