Aldoxime → 2-Fluoro-4-(2-(3-methylisoxazol-5-yl)pyridin-4-yloxy)benzenamine

HRID 450472

反応式

HRID 450472 の反応式
[CH:1](=[N:3][OH:4])[CH3:2].C(N(CC)CC)C.[C:12]([C:14]1[CH:19]=[C:18]([O:20][C:21]2[CH:26]=[CH:25][C:24]([NH2:27])=[C:23]([F:28])[CH:22]=2)[CH:17]=[CH:16][N:15]=1)#[CH:13].ClN1C(=O)CCC1=O>C1COCC1.CCOC(C)=O.O>[F:28][C:23]1[CH:22]=[C:21]([O:20][C:18]2[CH:17]=[CH:16][N:15]=[C:14]([C:12]3[O:4][N:3]=[C:1]([CH3:2])[CH:13]=3)[CH:19]=2)[CH:26]=[CH:25][C:24]=1[NH2:27]

参加物

8

反応物 4

HCID 7863Aldoxime2 回HCID 8471TriethylamineHCID 31398Chlorosuccinimide2 回HCID 598255834-(2-Ethynylpyridin-4-yloxy)-2-fluorobenzenamine

生成物 1

HCID 598255812-Fluoro-4-(2-(3-methylisoxazol-5-yl)pyridin-4-yloxy)benzenamine収率 23.1%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
130 °C

実験手順

Acetaldoxime (0.078 g, 1.321 mmol) and triethylamine (0.246 ml, 1.761 mmol) were added to a solution of 4-(2-ethynylpyridin-4-yloxy)-2-fluorobenzenamine (0.201 g, 0.881 mmol) in THF (4 mL) in a microwave reaction vial. To this solution was added 1-chloropyrrolidine-2,5-dione (0.176 g, 1.32 mmol) and the mixture was stirred at 130° C. for 45 min under microwave irradiation. An additional 1.5 eq each of acetaldoxime and 1-chloropyrrolidine-2,5-dione were added and the reaction heated for an additional 45 min at 130° C. This process was repeated one more time. The mixture was poured into a biphasic solution of water (40 mL) and EtOAc (30 mL). The organic layer was separated and the aqueous layer was extracted with EtOAc (2×20 ml). The combined organics were washed with brine, dried (Na2SO4), concentrated in vacuo and purified by column chromatography (EtOAc-hexanes) to afford 2-fluoro-4-(2-(3-methylisoxazol-5-yl)pyridin-4-yloxy)benzenamine (58 mg, 23% yield) as light red colored residue. MS (ESI) m/z: 286.1 (M+H+).

後処理

  1. temperaturethe reaction heated for an additional 45 min at 130° C
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with EtOAc (2×20 ml)
  4. washThe combined organics were washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. custompurified by column chromatography (EtOAc-hexanes)

出典と根拠

ORDレコード
ord-6ae99d6367eb4e3ab7485053c800488d
出典データセット
uspto-grants-2013_07
特許番号
US08486951B2

関連ノート

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