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Diisopropylethylamine → N-(3-((4S,6S)-2-benzamido-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-5-methoxypyrazine-2-carboxamide

HRID 930280
ノート
印刷プレビュー

反応式

HRID 930280 の反応式
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([F:29])=[C:6]([C@:8]2([CH2:27][F:28])[CH2:13][C@@H:12]([C:14]([F:17])([F:16])[F:15])[O:11][C:10]([NH:18][C:19](=[O:26])[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[N:9]2)[CH:7]=1.[CH3:30][O:31][C:32]1[N:33]=[CH:34][C:35]([C:38](O)=[O:39])=[N:36][CH:37]=1.F[P-](F)(F)(F)(F)F.CN(C(N(C)C)=[N+]1C2C(=NC=CC=2)[N+]([O-])=N1)C.C(N(C(C)C)CC)(C)C>CN(C=O)C.O.CCOC(C)=O>[C:19]([NH:18][C:10]1[O:11][C@H:12]([C:14]([F:15])([F:16])[F:17])[CH2:13][C@:8]([C:6]2[CH:7]=[C:2]([NH:1][C:38]([C:35]3[CH:34]=[N:33][C:32]([O:31][CH3:30])=[CH:37][N:36]=3)=[O:39])[CH:3]=[CH:4][C:5]=2[F:29])([CH2:27][F:28])[N:9]=1)(=[O:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

8

反応物 4

HCID 81531DiisopropylethylamineHCID 457898115-Methoxy-2-pyrazinecarboxylic acidHCID 86732108N-((4S,6S)-4-(5-amino-2-fluorophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamideHCID 178484293HCID 178484293、化合物

生成物 1

HCID 86732110N-(3-((4S,6S)-2-benzamido-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-5-methoxypyrazine-2-carboxamide

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of crude N-((4S,6S)-4-(5-amino-2-fluorophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamide (1k, 0.25 g, 0.605 mmol, step 9) in DMF (3 ml) was added 5-methoxypyrazine-2-carboxylic acid (0.117 g, 0.756 mmol, Ark Pharm), 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (0.345 g, 0.907 mmol, Oakwood Products) and di-isopropylethylamine (0.156 g, 1.210 mmol, Aldrich). The reaction was stirred at ambient temperature for 10 minutes. The reaction was diluted with water and EtOAc. The organic layer was separated and washed sequentially with aqueous saturated sodium bicarbonate solution, 1 M aqueous LiCl solution, and brine. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The crude material was purified via silica gel flash chromatography using a gradient of 0-45% EtOAc in hexanes to afford the title compound as a white solid (0.110 g, 0.2 mmol, 33% overall yield for this step and steps 9 in Example 1). MS m/z=550.0 [M+H]+. Calculated for C25H20F5N5O4: 549.449

後処理

  1. customThe organic layer was separated
  2. washwashed sequentially with aqueous saturated sodium bicarbonate solution, 1 M aqueous LiCl solution, and brine
  3. dry with materialThe organic layer was dried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe crude material was purified via silica gel flash chromatography

出典と根拠

ORDレコード
ord-6777f98723194166bfdea2bbab74638d
出典データセット
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09296734B2

反応ノート

読み込み中…

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