Methyl iodide → HCID 58109280、化合物

HRID 2037540ノート

反応式

HRID 2037540 の反応式
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([N:17]2[CH2:22][CH2:21][C@:20]([CH2:30][CH2:31][NH:32][C:33](=[O:35])[CH3:34])([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)[O:19][C:18]2=[O:36])[CH3:16])=[CH:11][CH:10]=1.[H-].[Na+].I[CH3:40]>O1CCCC1>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([N:17]2[CH2:22][CH2:21][C@:20]([CH2:30][CH2:31][N:32]([CH3:40])[C:33](=[O:35])[CH3:34])([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)[O:19][C:18]2=[O:36])[CH3:16])=[CH:11][CH:10]=1

参加物

5

反応物 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 53473320HCID 53473320、化合物

生成物 1

HCID 58109280HCID 58109280、化合物収率 15%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

A solution of N-(2-((R)-3-((S)-1-(2′,4′-difluorobiphenyl-4-yl)ethyl)-6-(4-fluorophenyl)-2-oxo-1,3-oxazinan-6-yl)ethyl)acetamide (60 mg, 0.121 mmol) in tetrahydrofuran anhydrous (5 mL) was added sodium hydride (15 mg, 0.605 mmol) at 0° C. and then stirred for 30 minutes at the same temperature. Iodomethane (86 mg, 0.605 mmol) was then added to the above mixture. The reaction mixture was stirred at rt for a further 8 h. The reaction mixture was poured into ice/water and extracted with EtOAc. The combined organic phases were dried over Na2SO4, filtered and concentrated to afford the residue, which was purified by TLC and separated by preparative HPLC to give N-(2-((R)-3-((S)-1-(2′,4′-difluorobiphenyl-4-yl)ethyl)-6-(4-fluorophenyl)-2-oxo-1,3-oxazinan-6-yl)ethyl)-N-methylacetamide (9 mg, 15%). LC-MS Method 3 tR=1.43, min, m/z=511; 1H NMR (CDCl3): 1.26 (m, 1H), 1.56 (m, 3H), 1.96 (m, 1H), 2.04 (m, 3H), 2.22 (m, 4H), 2.83 (m, 1H), 2.94 (m, 3H), 3.36 (m, 1H), 5.69 (m, 1H), 6.87 (m, 2H), 7.04 (m, 4H), 7.26 (m, 5H).

後処理

  1. stirringThe reaction mixture was stirred at rt for a further 8 h
  2. extractionextracted with EtOAc
  3. dry with materialThe combined organic phases were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto afford the residue, which
  7. customwas purified by TLC
  8. customseparated by preparative HPLC

出典と根拠

ORDレコード
ord-f086808905594e6d9c6108330f6c20cd
出典データセット
uspto-grants-2013_11
特許番号
US08575156B2

反応ノート

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