Lithium Hydroxide → tert-butyl 6-(6-(6-(3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)-2,6-diazaspiro[3.3]heptane-2-carboxylate

HRID 449598Notes

Reaction equation

HRID 449598 reaction equation
C([O:4][CH2:5][C:6]1[C:11]([N:12]2[N:21]=[CH:20][C:19]3[C:14](=[C:15]([F:26])[CH:16]=[C:17]([C:22]([CH3:25])([CH3:24])[CH3:23])[CH:18]=3)[C:13]2=[O:27])=[CH:10][CH:9]=[CH:8][C:7]=1[C:28]1[CH:29]=[C:30]([NH:36][C:37]2[N:42]=[CH:41][C:40]([N:43]3[CH2:56][C:45]4([CH2:48][N:47]([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH2:46]4)[CH2:44]3)=[CH:39][CH:38]=2)[C:31](=[O:35])[N:32]([CH3:34])[N:33]=1)(=O)C.[Li+].[OH-]>O1CCOCC1>[C:52]([O:51][C:49]([N:47]1[CH2:46][C:45]2([CH2:56][N:43]([C:40]3[CH:41]=[N:42][C:37]([NH:36][C:30]4[C:31](=[O:35])[N:32]([CH3:34])[N:33]=[C:28]([C:7]5[CH:8]=[CH:9][CH:10]=[C:11]([N:12]6[N:21]=[CH:20][C:19]7[C:14](=[C:15]([F:26])[CH:16]=[C:17]([C:22]([CH3:23])([CH3:24])[CH3:25])[CH:18]=7)[C:13]6=[O:27])[C:6]=5[CH2:5][OH:4])[CH:29]=4)=[CH:38][CH:39]=3)[CH2:44]2)[CH2:48]1)=[O:50])([CH3:53])([CH3:54])[CH3:55]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 66742494tert-butyl 6-(6-(6-(2-(acetoxymethyl)-3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)phenyl)-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)-2,6-diazaspiro[3.3]heptane-2-carboxylate

Product 1

HCID 66742571tert-butyl 6-(6-(6-(3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)-2,6-diazaspiro[3.3]heptane-2-carboxylateYield 34%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
25 °C

Procedure

In a 250 mL round-bottomed flask, tert-butyl 6-(6-(6-(2-(acetoxymethyl)-3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)phenyl)-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)-2,6-diazaspiro[3.3]heptane-2-carboxylate (530 mg, 693 μmol) was combined with dioxane (15 ml) and 1M LiOH (3 ml) to give a dark brown solution. The reaction mixture was stirred at 25° C. for 4 h. The crude reaction mixture was concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 220 g, 0% to 4% MeOH in DCM) to afford 0.169 g (34%) of the title compound as a light yellow powder. (M+H)'=723 m/e. 1H NMR (300 MHz, CHLOROFORM-d) δ: 8.36 (s, 1H), 8.26 (d, J=2.6 Hz, 1H), 8.19 (s, 1H), 7.37-7.69 (m, 6H), 6.84-6.94 (m, 1H), 6.80 (d, J=3.0 Hz, 1H), 4.39 (d, J=6.8 Hz, 2H), 4.08 (s, 4H), 3.96 (s, 4H), 3.85 (s, 3H), 1.42 (s, 9H), 1.39 (s, 9H).

Workup

  1. customto give a dark brown solution
  2. customThe crude reaction mixture
  3. concentrationwas concentrated in vacuo
  4. customThe crude material was purified by flash chromatography (silica gel, 220 g, 0% to 4% MeOH in DCM)

Sources & evidence

ORD record
ord-03593be80ee748c6a7542a67c5663c6b
Source dataset
uspto-grants-2013_07
Patent number
US08481540B2

Reaction notes

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