Pyridine → HCID 86267373、化合物

HRID 2278994ノート

反応式

HRID 2278994 の反応式
[C:1](Cl)(Cl)=[O:2].[CH3:5][O:6][C:7]1([CH2:10][CH2:11][N:12]2[CH2:16][CH2:15][NH:14][C:13]2=[O:17])[CH2:9][CH2:8]1.N1C=CC=CC=1.[CH3:24][N:25]1[CH:29]=[C:28]([C:30]2[CH:35]=[C:34]([O:36][C:37]3[CH:38]=[CH:39][C:40]([NH2:43])=[N:41][CH:42]=3)[CH:33]=[CH:32][N:31]=2)[CH:27]=[N:26]1>C(Cl)Cl.O>[CH3:5][O:6][C:7]1([CH2:10][CH2:11][N:12]2[CH2:16][CH2:15][N:14]([C:13]([NH:43][C:40]3[CH:39]=[CH:38][C:37]([O:36][C:34]4[CH:33]=[CH:32][N:31]=[C:30]([C:28]5[CH:27]=[N:26][N:25]([CH3:24])[CH:29]=5)[CH:35]=4)=[CH:42][N:41]=3)=[O:17])[C:1]2=[O:2])[CH2:8][CH2:9]1

参加物

7

反応物 4

HCID 1049PyridineHCID 6371PhosgeneHCID 593227775-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)pyridin-2-amineHCID 90426481HCID 90426481、化合物

生成物 1

HCID 86267373HCID 86267373、化合物収率 24%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒3 回

実験手順

A 0° C. solution of phosgene (20% in toluene, 0.711 mL, 0.980 mmol) in DCM (6 mL) was treated slowly drop-wise with a solution of Example B9 (0.129 g, 0.700 mmol) and pyridine (0.113 mL, 1.400 mmol) in DCM (2 mL), warmed to RT, stirred for 0.5 h, then concentrated to dryness. The residue was dissolved in DCM (2 mL), added to a 0° C. solution of Example A2 (0.058 g, 0.218 mmol) and TEA (0.091 mL, 0.654 mmol) in DCM (1 mL), warmed to RT and stirred for 0.5 h. The mixture was treated with water, stirred for 15 min and the layers separated. The organic layer was washed with additional water (2×), dried over MgSO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to afford 3-(2-(1-methoxycyclopropyl)ethyl)-N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide (25 mg, 24%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 10.99 (s, 1 H), 8.37 (d, J=5.7 Hz, 1 H), 8.25 (s, 1 H), 8.22 (d, J=2.9 Hz, 1 H), 8.07 (d, J=9.0 Hz, 1 H), 7.96 (d, J=0.7 Hz, 1 H), 7.72 (dd, J=9.0, 2.9 Hz, 1 H), 7.22 (d, J=2.4 Hz, 1 H), 6.69 (dd, J=5.7, 2.4 Hz, 1 H), 3.84 (s, 3 H), 3.80 (m, 2 H), 3.50 (m, 2 H), 3.34 (m, 2 H), 3.17 (s, 3 H), 1.77 (t, J=7.4 Hz, 2 H), 0.67 (m, 2 H), 0.42 (m, 2 H); MS (ESI) m/z: 478.2 (M+H+).

後処理

  1. concentrationconcentrated to dryness
  2. dissolutionThe residue was dissolved in DCM (2 mL)
  3. temperaturewarmed to RT
  4. stirringstirred for 0.5 h
  5. stirringstirred for 15 min
  6. customthe layers separated
  7. washThe organic layer was washed with additional water (2×)
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated to dryness
  10. custompurified via silica gel chromatography (MeOH/DCM)

出典と根拠

ORDレコード
ord-584ecc6f28464e4f8e3e9529dd71158a
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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