Lithium Hydroxide → 6-Tert-butyl-8-fluoro-2-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-(morpholine-4-carbonyl)-2-pyridyl]amino]-6-oxo-pyridazin-3-yl]-2-pyridyl]phthalazin-1-one

HRID 407656Notes

Reaction equation

HRID 407656 reaction equation
C([O:4][CH2:5][C:6]1[C:7]([N:35]2[N:44]=[CH:43][C:42]3[C:37](=[C:38]([F:49])[CH:39]=[C:40]([C:45]([CH3:48])([CH3:47])[CH3:46])[CH:41]=3)[C:36]2=[O:50])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]([N:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)=[O:26])=[CH:21][N:20]=2)[C:15](=[O:33])[N:14]([CH3:34])[N:13]=1)(=O)C.[OH-].[Li+]>C1COCC1.C(O)(C)C.O>[C:45]([C:40]1[CH:41]=[C:42]2[C:37](=[C:38]([F:49])[CH:39]=1)[C:36](=[O:50])[N:35]([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:27]5[CH2:28][CH2:29][O:30][CH2:31][CH2:32]5)=[O:26])=[CH:21][N:20]=4)[C:15](=[O:33])[N:14]([CH3:34])[N:13]=3)[CH:10]=[CH:9][N:8]=1)[N:44]=[CH:43]2)([CH3:48])([CH3:46])[CH3:47]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 86683942(2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(5-(morpholine-4-carbonyl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)pyridin-3-yl)methyl Acetate

Product 1

HCID 712578546-Tert-butyl-8-fluoro-2-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-(morpholine-4-carbonyl)-2-pyridyl]amino]-6-oxo-pyridazin-3-yl]-2-pyridyl]phthalazin-1-oneYield 80%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 22597222Tetrahydrofuran 2-propanolSolvent

Conditions

Temperature
30 °C

Procedure

A mixture of 116e (150 mg, 0.20 mmol) and lithium hydroxide (85 mg, 2.0 mmol) in THF/i-propanol (5/3 mL) and water (2 mL) was stirred at 30° C. for 1 h. The mixture was evaporated under reduce pressure and the residue was extracted with ethyl acetate (3×20 mL). The combined ethyl acetate extract was concentrated under reduced pressure and the residue was purified by reverse-phase prep-HPLC to afford 116 (80 mg, 80%) as a white solid. MS-ESI: [M+H]+ 641.3. 1H NMR (500 MHz, CDCl3) δ 8.78 (s, 1H), 8.75 (d, J=5.0 Hz, 1H), 8.47 (s, 1H), 8.45 (d, J=2.0 Hz, 1H), 8.34 (d, J=3.0 Hz, 1H), 7.79 (dd, J=2.0, 8.0 Hz, 1H), 7.64 (d, J=4.5 Hz, 1H), 7.57 (s, 1H), 7.52 (dd, J=1.5, 12.5 Hz, 1H), 7.02 (d, J=8.5 Hz, 1H), 4.57-4.55 (m, 2H), 3.94 (s, 3H), 3.81-3.75 (m, 6H), 1.64-1.62 (m, 2H), 1.44 (s, 9H).

Workup

  1. customThe mixture was evaporated
  2. extractionthe residue was extracted with ethyl acetate (3×20 mL)
  3. extractionThe combined ethyl acetate extract
  4. concentrationwas concentrated under reduced pressure
  5. customthe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-45b152a74f47433da676298e8763907c
Source dataset
uspto-grants-2014_06
Patent number
US08754077B2

Reaction notes

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