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Lithium Hydroxide → 6-tert-Butyl-2-{3-[5-(5-ethanesulfonyl-pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl]-2-hydroxymethyl-phenyl}-8-fluoro-2H-phthalazin-1-one

HRID 1431097
ノート
印刷プレビュー

反応式

HRID 1431097 の反応式
C([O:4][CH2:5][C:6]1[C:11]([C:12]2[CH:17]=[C:16]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([S:25]([CH2:28][CH3:29])(=[O:27])=[O:26])=[CH:21][N:20]=3)[C:15](=[O:30])[N:14]([CH3:31])[N:13]=2)=[CH:10][CH:9]=[CH:8][C:7]=1[N:32]1[N:41]=[CH:40][C:39]2[C:34](=[C:35]([F:46])[CH:36]=[C:37]([C:42]([CH3:45])([CH3:44])[CH3:43])[CH:38]=2)[C:33]1=[O:47])(=O)C.[Li+].[OH-]>O1CCOCC1>[C:42]([C:37]1[CH:38]=[C:39]2[C:34](=[C:35]([F:46])[CH:36]=1)[C:33](=[O:47])[N:32]([C:7]1[CH:8]=[CH:9][CH:10]=[C:11]([C:12]3[CH:17]=[C:16]([NH:18][C:19]4[CH:24]=[CH:23][C:22]([S:25]([CH2:28][CH3:29])(=[O:26])=[O:27])=[CH:21][N:20]=4)[C:15](=[O:30])[N:14]([CH3:31])[N:13]=3)[C:6]=1[CH2:5][OH:4])[N:41]=[CH:40]2)([CH3:43])([CH3:44])[CH3:45]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

4

反応物 2

HCID 3939Lithium HydroxideHCID 667427742-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(5-(5-(ethylsulfonyl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate

生成物 1

HCID 566556686-tert-Butyl-2-{3-[5-(5-ethanesulfonyl-pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl]-2-hydroxymethyl-phenyl}-8-fluoro-2H-phthalazin-1-one収率 54%

試薬・触媒・溶媒 1

HCID 31275
1,4-Dioxane
溶媒

反応条件

温度
25 °C

実験手順

In a 250 mL round-bottomed flask, 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(5-(5-(ethylsulfonyl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate (159 mg, 241 μmol) was combined with dioxane (5 ml) and 1M LiOH (1 ml) to give a brown solution. The reaction mixture was stirred at 25° C. for 18 h. The crude reaction mixture was concentrated in vacuo. The residue was partitioned between water and DCM. The organic layer was dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 24 g, 0% to 4% MeOH in DCM) to afford 0.039 g (54%) of the title compound as a tan solid. (M−H)+=617 m/e. 1H NMR (300 MHz, CHLOROFORM-d) δ: 8.85 (d, J=2.3 Hz, 1H), 8.79 (s, 1H), 8.63 (s, 1H), 8.30 (d, J=2.3 Hz, 1H), 8.06 (dd, J=8.7, 2.3 Hz, 1H), 7.43-7.73 (m, 5H), 7.07 (d, J=8.7 Hz, 1H), 4.45 (s, 2H), 3.94 (s, 3H), 3.15 (d, J=7.2 Hz, 2H), 1.44 (s, 9H), 1.33 (t, J=7.2 Hz, 3H).

後処理

  1. customto give a brown solution
  2. customThe crude reaction mixture
  3. concentrationwas concentrated in vacuo
  4. customThe residue was partitioned between water and DCM
  5. dry with materialThe organic layer was dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by flash chromatography (silica gel, 24 g, 0% to 4% MeOH in DCM)

出典と根拠

ORDレコード
ord-d747d0917201455b84e4fa79e186742e
出典データセット
uspto-grants-2015_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08940741B2

反応ノート

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