Water → 6-Tert-butyl-2-[4-[5-[(5-ethyl-1-methyl-pyrazol-3-yl)amino]-1-methyl-6-oxo-3-pyridyl]-3-(hydroxymethyl)-2-pyridyl]-8-fluoro-phthalazin-1-one

HRID 407677Notes

Reaction equation

HRID 407677 reaction equation
C([O:4][CH2:5][C:6]1[C:7]([N:29]2[N:38]=[CH:37][C:36]3[C:31](=[C:32]([F:43])[CH:33]=[C:34]([C:39]([CH3:42])([CH3:41])[CH3:40])[CH:35]=3)[C:30]2=[O:44])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([NH:18][C:19]2[CH:23]=[C:22]([CH2:24][CH3:25])[N:21]([CH3:26])[N:20]=2)[C:15](=[O:27])[N:14]([CH3:28])[CH:13]=1)(=O)C.[OH-].[Li+].O>C1COCC1.C(O)(C)C.O>[C:39]([C:34]1[CH:35]=[C:36]2[C:31](=[C:32]([F:43])[CH:33]=1)[C:30](=[O:44])[N:29]([C:7]1[C:6]([CH2:5][OH:4])=[C:11]([C:12]3[CH:17]=[C:16]([NH:18][C:19]4[CH:23]=[C:22]([CH2:24][CH3:25])[N:21]([CH3:26])[N:20]=4)[C:15](=[O:27])[N:14]([CH3:28])[CH:13]=3)[CH:10]=[CH:9][N:8]=1)[N:38]=[CH:37]2)([CH3:40])([CH3:41])[CH3:42]

Participants

5

Reactant 3

HCID 962WaterHCID 3939Lithium HydroxideHCID 86683960(2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(5-(5-ethyl-1-methyl-1H-pyrazol-3-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)pyridin-3-yl)methyl Acetate

Product 1

HCID 866839616-Tert-butyl-2-[4-[5-[(5-ethyl-1-methyl-pyrazol-3-yl)amino]-1-methyl-6-oxo-3-pyridyl]-3-(hydroxymethyl)-2-pyridyl]-8-fluoro-phthalazin-1-oneYield 35.1%

Reagents, catalysts & solvents 1

HCID 22722550Tetrahydrofuran water isopropanolSolvent

Procedure

To a solution of 122c (150 mg, 0.25 mmol) in THF/i-propanol/water (2.5/1/0.5 mL) was added lithium hydroxide (70 mg, 2.5 mmol) at 35° C. After the reaction was stirred for 3 h, LCMS indicated the reaction was completed. The mixture was poured into water (15 mL) and extracted with dichloromethane (3×20 mL). The combined organic layer was washed with brine (30 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue solid was purified by reverse-phase prep-HPLC to afford 122 (49 mg, 35%) as a white solid. MS-ESI: [M+H]+ 557.8. 1H NMR (500 MHz, CDCl3) δ 8.59 (d, J=5.0 Hz, 1H), 8.51 (d, J=2.5 Hz, 1H), 7.92 (d, J=2.0 Hz, 1H), 7.88 (d, J=1.5 Hz, 1H), 7.73 (m, 1H), 7.64 (d, J=5.0 Hz, 1H), 7.41 (d, J=1.5 Hz, 1H), 5.92 (s, 1H), 4.59 (s, 2H), 3.72 (s, 3H), 3.68 (s, 3H), 2.64 (m, 2H), 1.47 (s, 9H), 1.27 (t, J=2.5, 3H)

Workup

  1. extractionextracted with dichloromethane (3×20 mL)
  2. washThe combined organic layer was washed with brine (30 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue solid was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-d776f2b1c8024f5aa41d5fff10018834
Source dataset
uspto-grants-2014_06
Patent number
US08754077B2

Reaction notes

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