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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
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HRID 1431097 반응식
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]
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참가 물질

4

반응물 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

생성물 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-one수율 54%

시약·촉매·용매 1

HCID 31275
1,4-Dioxane
용매

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온도
25 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-d747d0917201455b84e4fa79e186742e
출처 데이터셋
uspto-grants-2015_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08940741B2

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