Lithium Hydroxide → HCID 56655452, compound

HRID 1431082Notes

Reaction equation

HRID 1431082 reaction equation
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]([C:25](=[O:29])[N:26]([CH3:28])[CH3:27])=[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[C:6]([CH2:5][OH:4])=[C:11]([C:12]3[CH:17]=[C:16]([NH:18][C:19]4[CH:24]=[CH:23][C:22]([C:25]([N:26]([CH3:28])[CH3:27])=[O:29])=[CH:21][N:20]=4)[C:15](=[O:30])[N:14]([CH3:31])[N:13]=3)[CH:10]=[CH:9][CH:8]=1)[N:41]=[CH:40]2)([CH3:45])([CH3:43])[CH3:44]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 66742925HCID 66742925, compound

Product 1

HCID 56655452HCID 56655452, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
25 °C

Procedure

In a 500 mL round-bottomed flask, 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(5-(5-(dimethylcarbamoyl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate (1.142 g, 1.79 mmol) was combined with dioxane (25 ml) and 1M LiOH (10 ml) to give a light yellow suspension. The reaction mixture was stirred at 25° C. for 17 h. The crude reaction mixture was concentrated in vacuo. The residue was partitioned between DCM and water. An emulsion was obtained and the aqueous was extracted exhaustively with DCM. The organic layers were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 120 g, 0% to 4% MeOH in DCM) to afford 0.471 g (44%) of the title compound as a white solid. (M+H)+=598 m/e. 1H NMR (300 MHz, CHLOROFORM-d) δ: 8.68 (s, 1H), 8.46 (d, J=2.6 Hz, 2H), 8.29 (d, J=2.6 Hz, 1H), 7.79 (dd, J=8.3, 2.3 Hz, 1H), 7.64-7.69 (m, 1H), 7.53-7.63 (m, 3H), 7.50 (t, J=2.1 Hz, 1H), 7.47 (d, J=1.5 Hz, 1H), 7.00 (d, J=8.7 Hz, 1H), 4.43 (s, 2H), 3.92 (s, 3H), 3.11 (s, 6H), 1.43 (s, 9H).

Workup

  1. customto give a light yellow suspension
  2. customThe crude reaction mixture
  3. concentrationwas concentrated in vacuo
  4. customThe residue was partitioned between DCM and water
  5. customAn emulsion was obtained
  6. extractionthe aqueous was extracted exhaustively with DCM
  7. dry with materialThe organic layers were dried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customThe crude material was purified by flash chromatography (silica gel, 120 g, 0% to 4% MeOH in DCM)

Sources & evidence

ORD record
ord-49d68931d07e4dbbb6ab0b1a1753815a
Source dataset
uspto-grants-2015_01
Patent number
US08940741B2

Reaction notes

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