Hydrochloric Acid → 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(4-methyl-6-(4-methyl-6-oxo-1,6-dihydropyridin-3-yl)pyridin-2-yl)cyclopropanecarboxamide

HRID 869940ノート

反応式

HRID 869940 の反応式
[F:1][C:2]1([F:33])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([NH:16][C:17]4[N:22]=[C:21]([C:23]5[CH:24]=[N:25][C:26]([O:30]C)=[CH:27][C:28]=5[CH3:29])[CH:20]=[C:19]([CH3:32])[CH:18]=4)=[O:15])[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1.Cl>O1CCOCC1>[F:33][C:2]1([F:1])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([NH:16][C:17]4[CH:18]=[C:19]([CH3:32])[CH:20]=[C:21]([C:23]5[C:28]([CH3:29])=[CH:27][C:26](=[O:30])[NH:25][CH:24]=5)[N:22]=4)=[O:15])[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1

参加物

4

反応物 2

HCID 313Hydrochloric AcidHCID 68794099HCID 68794099、化合物

生成物 1

HCID 710530731-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(4-methyl-6-(4-methyl-6-oxo-1,6-dihydropyridin-3-yl)pyridin-2-yl)cyclopropanecarboxamide収率 19.2%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
90 °C

実験手順

To 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(6′-methoxy-4,4′-dimethyl-2,3′-bipyridin-6-yl)cyclopropanecarboxamide (38 mg, 0.083 mmol) in 1,4-dioxane (1.5 mL) was added aqueous 4 M HCl (225 μL, 0.899 mmol) drop-wise. The reaction was stirred at 90° C. for 1.5 hours. The reaction was allowed to cool down to room temperature and then quenched with Et3N. The solvent was evaporated under reduced pressure. The crude compound was dissolved in ethyl acetate and washed with water (2×) and brine (1×). The organic layer was dried over Na2SO4, filtered and evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel (0-10% methanol in dichloromethans) to yield 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(4-methyl-6-(4-methyl-6-oxo-1,6-dihydropyridin-3-yl)pyridin-2-yl)cyclopropanecarboxamide as a white solid (7 mg, 19%). ESI-MS m/z calc. 439.41. found 440.5 (M+1)+. Retention time 1.60 minutes.

後処理

  1. temperatureto cool down to room temperature
  2. customquenched with Et3N
  3. customThe solvent was evaporated under reduced pressure
  4. dissolutionThe crude compound was dissolved in ethyl acetate
  5. washwashed with water (2×) and brine (1×)
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customThe crude product was purified by column chromatography on silica gel (0-10% methanol in dichloromethans)

出典と根拠

ORDレコード
ord-774764f2a297498fb910908dcb4f6164
出典データセット
uspto-grants-2015_03
特許番号
US08969386B2

反応ノート

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