Dimethylformamide → (2S)-methyl 6-(1-(1-(tert-butoxycarbonyl)-3-methoxypiperidin-4-yl)-1H-pyrazol-4-yl)-5-cyclobutoxy-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate

HRID 1051669ノート

反応式

HRID 1051669 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[C:20]([O:34][CH:35]4[CH2:38][CH2:37][CH2:36]4)=[C:21]4[C:26](=[CH:27][CH:28]=3)[N:25]([C:29]([O:31][CH3:32])=[O:30])[C@@H:24]([CH3:33])[CH2:23][CH2:22]4)[CH:16]=[N:15]2)[CH:10]([OH:39])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:40]N(C)C=O.[H-].[Na+].CI>O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[C:20]([O:34][CH:35]4[CH2:38][CH2:37][CH2:36]4)=[C:21]4[C:26](=[CH:27][CH:28]=3)[N:25]([C:29]([O:31][CH3:32])=[O:30])[C@@H:24]([CH3:33])[CH2:23][CH2:22]4)[CH:16]=[N:15]2)[CH:10]([O:39][CH3:40])[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

参加物

6

反応物 4

HCID 6228DimethylformamideHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 118086271methyl (2S)-6-(1-[1-[(tert-butoxy)carbonyl]-3-hydroxypiperidin-4-yl]-1H-pyrazol-4-yl)-5-cyclobutoxy-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate

生成物 1

HCID 118075809(2S)-methyl 6-(1-(1-(tert-butoxycarbonyl)-3-methoxypiperidin-4-yl)-1H-pyrazol-4-yl)-5-cyclobutoxy-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate収率 31%

試薬・触媒・溶媒 1

HCID 962Water溶媒

実験手順

A 50-mL round-bottom flask was charged with methyl (2S)-6-(1-[1-[(tert-butoxy)carbonyl]-3-hydroxypiperidin-4-yl]-1H-pyrazol-4-yl)-5-cyclobutoxy-2-methyl-1,2,3,4-tetrahydroquinoline-1-carboxylate (250 mg, 0.46 mmol,) and N,N-dimethylformamide (5 mL). Sodium hydride (78 mg, 3.25 mmol,) was added, and the mixture stirred at room temperature for 30 minutes. Methyl iodide (0.079 mL, 1.28 mmol) was added, and the resulting solution stirred for 4 h at room temperature. The reaction mixture was then poured into 20 mL of water and extracted with ethyl acetate (3×20 mL). The organic layers were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified via column chromatography on silica gel (eluting with 1:5, ethyl acetate/petroleum ether) to afford (2S)-methyl 6-(1-(1-(tert-butoxycarbonyl)-3-methoxypiperidin-4-yl)-1H-pyrazol-4-yl)-5-cyclobutoxy-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate (80 mg, 31%) as colorless oil. MS (ESI, pos. ion) m/z 555 [M+H]+.

後処理

  1. stirringthe resulting solution stirred for 4 h at room temperature
  2. extractionextracted with ethyl acetate (3×20 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified via column chromatography on silica gel (eluting with 1:5, ethyl acetate/petroleum ether)

出典と根拠

ORDレコード
ord-87e8c5ad8a944885923084e7b3a68315
出典データセット
uspto-grants-2016_07
特許番号
US09388161B2

反応ノート

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