Oxalyl chloride → N-((5-((2-acetamidopyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)tetrahydro-2H-pyran-4-carboxamide

HRID 626546ノート

反応式

HRID 626546 の反応式
[O:1]1[CH2:6][CH2:5][CH:4]([C:7]([NH2:9])=[O:8])[CH2:3][CH2:2]1.C(Cl)(=O)[C:11](Cl)=[O:12].[NH2:16][C:17]1[N:22]=[CH:21][C:20]([O:23][C:24]2[CH:29]=[CH:28][N:27]=[C:26]([NH:30][C:31](=[O:33])[CH3:32])[CH:25]=2)=[CH:19][CH:18]=1>ClCCCl.C1COCC1>[C:31]([NH:30][C:26]1[CH:25]=[C:24]([O:23][C:20]2[CH:19]=[CH:18][C:17]([NH:16][C:11]([NH:9][C:7]([CH:4]3[CH2:5][CH2:6][O:1][CH2:2][CH2:3]3)=[O:8])=[O:12])=[N:22][CH:21]=2)[CH:29]=[CH:28][N:27]=1)(=[O:33])[CH3:32]

参加物

6

反応物 3

HCID 65578Oxalyl chlorideHCID 13197203Oxane-4-carboxamideHCID 90410482N-(4-((6-aminopyridin-3-yl)oxy)pyridin-2-yl)acetamide

生成物 1

HCID 86272277N-((5-((2-acetamidopyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)tetrahydro-2H-pyran-4-carboxamide収率 52.4%

試薬・触媒・溶媒 2

HCID 111,2-Dichloroethane溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
80 °C

実験手順

A solution of Example B5 (0.095 g, 0.737 mmol) in DCE (3 mL) was treated with oxalyl chloride (0.129 mL, 1.474 mmol) and heated at 80° C. for 3 h. The mixture was cooled to RT, concentrated to dryness, treated with a solution of Example A2 (0.09 g, 0.368 mmol) and TEA (0.205 mL, 1.474 mmol) in THF (4 mL) and stirred at RT for 0.5 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 (MeOH/DCM). The material was suspended in MeCN/H2O, frozen and lyophilized to afford N-((5-((2-acetamidopyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)tetrahydro-2H-pyran-4-carboxamide (77 mg, 52%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.05 (s, 1H), 10.88 (s, 1H), 10.56 (s, 1H), 8.24 (d, J=2.9 Hz, 1H), 8.18 (d, J=5.7 Hz, 1H), 8.07 (d, J=9.0 Hz, 1H), 7.72 (dd, J=9.0, 2.9 Hz, 1H), 7.64 (d, J=2.4 Hz, 1H), 6.68 (dd, J=5.7, 2.4 Hz, 1H), 3.87 (m, 2H), 3.29-3.25 (m, 2H), 2.72-2.64 (m, 1H), 2.02 (s, 3H), 1.71 (m, 2H), 1.66-1.54 (m, 2H); MS (ESI) m/z: 400.2 (M+H+).

後処理

  1. temperatureThe mixture was cooled to RT
  2. concentrationconcentrated to dryness
  3. additionThe mixture was treated with satd
  4. extractionNaHCO3, extracted with EtOAc (2×)
  5. washthe combined organics were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated to dryness
  8. custompurified via silica gel chromatography (MeOH/DCM)
  9. temperaturefrozen

出典と根拠

ORDレコード
ord-4af7ef639ad744528129e59a9be4276a
出典データセット
uspto-grants-2016_04
特許番号
US09309224B2

反応ノート

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